WO2004058754A1 - Benzoazolypiperazine derivatives having mglur1- and mglur5-antagonistic activity - Google Patents

Benzoazolypiperazine derivatives having mglur1- and mglur5-antagonistic activity Download PDF

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Publication number
WO2004058754A1
WO2004058754A1 PCT/US2003/041100 US0341100W WO2004058754A1 WO 2004058754 A1 WO2004058754 A1 WO 2004058754A1 US 0341100 W US0341100 W US 0341100W WO 2004058754 A1 WO2004058754 A1 WO 2004058754A1
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compound
halo
another embodiment
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PCT/US2003/041100
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French (fr)
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Qun Sun
Laykea Tafesse
Sam Victory
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Euro-Celtique S.A.
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Priority to NZ541415A priority Critical patent/NZ541415A/en
Priority to DE60320033T priority patent/DE60320033T2/en
Priority to YUP-2005/0498A priority patent/RS20050498A/en
Priority to DK03814351T priority patent/DK1583763T3/en
Priority to BR0317757-2A priority patent/BR0317757A/en
Priority to MXPA05006869A priority patent/MXPA05006869A/en
Priority to EA200501022A priority patent/EA200501022A1/en
Application filed by Euro-Celtique S.A. filed Critical Euro-Celtique S.A.
Priority to AU2003297506A priority patent/AU2003297506A1/en
Priority to SI200331239T priority patent/SI1583763T1/en
Priority to JP2005510054A priority patent/JP4680774B2/en
Priority to EP03814351A priority patent/EP1583763B1/en
Priority to CA2511509A priority patent/CA2511509C/en
Publication of WO2004058754A1 publication Critical patent/WO2004058754A1/en
Priority to IL169378A priority patent/IL169378A0/en
Priority to NO20053582A priority patent/NO20053582L/en
Priority to HR20050666A priority patent/HRP20050666B1/en
Priority to HK06110337.5A priority patent/HK1090033A1/en

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    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • Pain has been traditionally managed by administering non-opioid analgesics, such as acetylsalicylic acid, choline magnesium trisalicylate, acetaminophen, ibuprofen, fenoprofen, diflusinal, and naproxen; or opioid analgesics, including morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone, and oxymorphone.
  • opioid analgesics including morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone, and oxymorphone.
  • UI is associated with embarrassment, social stigmatization, depression and a risk of institutionalization (Herzo et al, Annu. Rev. Gerontol. Geriatr. 9:1 A (1989)). Economically, the costs of UI are great; in the United States alone, health-care costs associated with UI are over $15 billion per annum.
  • Antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate can be used to neutralize stomach acids. Antacids, however, can cause alkalosis, leading to nausea, headache, and weakness. Antacids can also interfere with the absorption of other drugs into the blood stream and cause diarrhea.
  • H 2 antagonists such as cimetidine, ranitidine, famotidine, and nizatidine are also used to treat ulcers. H 2 antagonists promote ulcer healing by reducing gastric acid and digestive-enzyme secretion elicited by histamine and other H 2 agonists in the stomach and duodenum. H 2 antagonists, however, can cause breast enlargement and impotence in men, mental changes (especially in the elderly), headache, dizziness, nausea, myalgia, diarrhea, rash, and fever.
  • Sucraflate is also used to treat ulcers.
  • Sucraflate adheres to epithelial cells and is believed to form a protective coating at the base of an ulcer to promote healing.
  • Sucraflate can cause constipation, dry mouth, and interfere with the absorption of other drugs.
  • Antibiotics are used when Helicobader pylori is the underlying cause of the ulcer. Often antibiotic therapy is coupled with the administration of bismuth compounds such as bismuth subsalicylate and colloidal bismuth citrate.
  • bismuth compounds are believed to enhance secretion of mucous and HCO 3 " , inhibit pepsin activity, and act as an antibacterial against H. pylori, higestion of bismuth compounds, however, can lead to elevated plasma concentrations of Bi +3 and can interfere with the absorption of other drugs.
  • Prostaglandin analogues such as misoprostal, inhibit secretion of acid and stimulate the secretion of mucous and bicarbonate and are also used to treat ulcers, especially ulcers in patients who require nonsteroidal anti-inflammatory drugs. Effective oral doses of prostaglandin analogues, however, can cause diarrhea and abdominal cramping. In addition, some prostaglandin analogues are abortifacients.
  • Carbenoxolone a mineral corticoid, can also be used to treat ulcers.
  • Carbenoxolone appears to alter the composition and quantity of mucous, thereby enhancing the mucosal barrier. Carbenoxolone, however, can lead to Na + and fluid retention, hypertension, hypokalemia, and impaired glucose tolerance.
  • Crohn's disease which can include regional enteritis, granulomatous ileitis, and ileocolitis, is a chronic inflammation of the intestinal wall. Crohn's disease occurs equally in both sexes and is more common in Jews of eastern-European ancestry. Most cases of Crohn's disease begin before age 30 and the majority start between the ages of 14 and 24. The disease typically affects the full thickness of the intestinal wall. Generally the disease affects the lowest portion of the small intestine (ileum) and the large intestine, but can occur in any part of the digestive tract.
  • Crohn's disease Early symptoms of Crohn's disease are chronic diarrhea, crampy abdominal pain, fever, loss of appetite, and weight loss. Complications associated with Crohn's disease include the development of intestinal obstructions, abnormal connecting channels (fistulas), and abscesses. The risk of cancer of the large intestine is increased in people who have
  • Crohn's disease Often Crohn's disease is associated with other disorders such as gallstones, inadequate absorption of nutrients, amyloidosis, arthritis, episcleritis, aphthous stomatitis, erythema nodosum, pyoderma gangrenosum, ankylosing spondylitis, sacroilitis, uveitis, and primary sclerosing cholangitis.
  • Cramps and diarrhea side effects associated with Crohn's disease, can be relieved by anticholinergic drugs, diphenoxylate, loperamide, deodorized opium tincture, or codeine. Generally, the drug is taken orally before a meal.
  • antibiotics are often administered to treat the symptoms of Crohn's disease.
  • the antibiotic metronidazole is often administered when the disease affects the large intestine or causes abscesses and fistulas around the anus.
  • Long-term use of metronidazole can damage nerves, resulting in pins-and-needles sensations in the arms and legs.
  • Sulfasalazine and chemically related drugs can suppress mild inflammation, especially in the large intestine. These drugs, however, are less effective in sudden, severe flare-ups.
  • Corticosteroids such as prednisone, reduce fever and diarrhea and relieve abdominal pain and tenderness.
  • Ulcerative colitis is a chronic disease in which the large intestine becomes inflamed and ulcerated, leading to episodes of bloody diarrhea, abdominal cramps, and fever. Ulcerative colitis usually begins between ages 15 and 30; however, a small group of people have their first attack between ages 50 and 70. Unlike Crohn's disease, ulcerative colitis never affects the small intestine and does not affect the full thickness of the intestine. The disease usually begins in the rectum and the sigmoid colon and eventually spreads partially or completely through out the large intestine. The cause of ulcerative colitis is unknown. Treatment of ulcerative colitis is directed to controlling iriflammation, reducing symptoms, and replacing lost fluids and nutrients.
  • Anticholinergic drugs and low doses of diphenoxylate or loperamide are administered for treating mild diarrhea. For more intense diarrhea higher doses of diphenoxylate or loperamide, or deodorized opium tincture or codeine are administered.
  • Sulfasalazine, olsalazie, prednisone, or mesalamine can be used to reduce inflammation.
  • Azathioprine and mercaptopurine have been used to maintain remissions in ulcerative-colitis patients who would otherwise need long-term corticosteroid treatment. In severe cases of ulcerative colitis the patient is hospitalized and given corticosteroids intravenously. People with severe rectal bleeding can require transfusions and intravenous fluids.
  • IBS is a disorder of motility of the entire gastrointestinal tract, causing abdominal pain, constipation, and/or diarrhea.
  • IBS affects three-times more women than men.
  • IBS stimuli such as stress, diet, drugs, hormones, or irritants can cause the gastrointestinal tract to contract abnormally.
  • IBS contractions of the gastrointestinal tract become stronger and more frequent, resulting in the rapid transit of food and feces through the small intestine, often leading to diarrhea.
  • Cramps result from the strong contractions of the large intestine and increased sensitivity of pain receptors in the large intestine.
  • IBS intracranial pressure
  • spastic-colon type is commonly triggered by eating, and usually produces periodic constipation and diarrhea with pain. Mucous often appears in the stool. The pain can come in bouts of continuous dull aching pain or cramps, usually in the lower abdomen. The person suffering from spastic- colon type IBS can also experience bloating, gas, nausea, headache, fatigue, depression, anxiety, and difficulty concentrating.
  • the second type of IBS usually produces painless diarrhea or constipation. The diarrhea can begin suddenly and with extreme urgency. Often the diarrhea occurs soon after a meal and can sometimes occur immediately upon awakening. Treatment of IBS typically involves modification of an IBS-patient's diet.
  • an IBS patient avoid beans, cabbage, sorbitol, and fructose.
  • a low-fat, high-fiber diet can also help some IBS patients.
  • Regular physical activity can also help keep the gastrointestinal tract functioning properly.
  • Drugs such as propantheline that slow the function of the gastrointestinal tract are generally not effective for treating IBS.
  • Antidiarrheal drugs such as diphenoxylate and loperamide, help with diarrhea. The Merck Manual of Medical Information 525-526 (R. Berkow ed., 1997).
  • drugs can cause physical and or psychological addiction.
  • Those most well known types of these drugs include opiates, such as heroin, opium, and morphine; sympathomimetics, including cocaine and amphetamines; sedative-hypnotics, including alcohol, benzodiazepines and barbiturates; and nicotine, which has effects similar to opioids and sympathomimetics.
  • Drug addiction is characterized by a craving or compulsion for taking the drug and an inability to limit its intake. Additionally, drug dependence is associated with drug tolerance, the loss of effect of the drug following repeated administration, and withdrawal, the appearance of physical and behavioral symptoms when the drug is not consumed. Sensitization occurs if repeated administration of a drug leads to an increased response to each dose.
  • U.S. Patent No. 5,556,838 to Mayer et al. discloses the use of nontoxic NMDA-blocking agents co-administered with an addictive substance to prevent the development of tolerance or withdrawal symptoms.
  • U.S. Patent No. 5,574,052 to Rose et al. discloses co- administration of an addictive substance with an antagonist to partially block the pharmacological effects of the substance.
  • U.S. Patent No. 5,075,341 to Mendelson et al. discloses the use of a mixed opiate agonist/antagonist to treat cocaine and opiate addiction.
  • U.S. Patent No. 5,232,934 to Downs discloses administration of 3-phenoxypyridine to treat addiction.
  • Imperato et al. disclose using a serotonin antagonist to treat chemical addiction.
  • U.S. Patent No. 5,556,837 to Nestler et. al. discloses infusing BDNF or NT-4 growth factors to inhibit or reverse neurological adaptive changes that correlate with behavioral changes in an addicted individual.
  • U.S. Patent. No. 5,762,925 to Sagan discloses implanting encapsulated adrenal medullary cells into an animal's central nervous system to inhibit the development of opioid intolerance.
  • Parkinson's disease is a clinical syndrome comprising bradykinesia (slowness and poverty of movement), muscular rigidity, resting tremor (which usually abates during voluntary movement), and an impairment of postural balance leading to disturbance of gait and falling.
  • the features of Parkinson's disease are a loss of pigmented, dopaminergic neurons of the substantia nigra pars compacta and the appearance of intracellular inclusions known as Lewy bodies (Goodman and Gillman 's The Pharmaceutical Basis of Therapeutics 506 (9 th ed. 1996)). Without treatment, Parkinson's disease progresses to a rigid akinetic state in which patients are incapable of caring for themselves. Death frequently results from complications of immobility, including aspiration pneumonia or pulmonary embolism.
  • Drugs commonly used for the treatment of Parkinson's disease include carbidopa/levodopa, pergolide, bromocriptine, selegiline, amantadine, and trihexyphenidyl hydrochloride.
  • Anxiety is a fear, apprehension, or dread of impending danger often accompanied by restlessness, tension, tachycardia, and dyspnea.
  • Other symptoms commonly associated with anxiety include depression, especially accompanied with dysthymic disorder (chronic "neurotic" depression); panic disorder; agoraphobia and other specific phobias; eating disorders; and many personality disorders.
  • anxiety is unattached to a clearly identified treatable primary illness. If a primary illness is found, however, it can be desirable to deal with the anxiety at the same time as the primary illness.
  • benzodiazepines are the most commonly used anti-anxiety agents for generalized anxiety disorder. Benzodiazepines, however, carry the risk of producing impairment of cognition and skilled motor functions, particularly in the elderly, which can result in confusion, delerium, and falls with fractures. Sedatives are also commonly prescribed for treating anxiety.
  • the azapirones such as buspirone, are also used to treat moderate anxiety. The azapirones, however, are less useful for treating severe anxiety accompanied with panic attacks.
  • Epilepsy is a disorder characterized by the tendency to have recurring seizures.
  • the etiology commonly consists of lesions in some part of the cortex, such as a tumor; developmental malformation; or damage due to trauma or stroke. In some cases the etiology is genetic.
  • An epileptic seizure can be triggered by repetitive sounds, flashing lights, video games, or touching certain parts of the body.
  • Epilepsy is typically treated with anti-seizure drugs. In epilepsy cases, where anti-seizure drugs are ineffective, and the defect in the brain is isolated to a small area of the brain, surgical removal of that part of the brain can be helpful in alleviating the seizures. In patients who have several sources for the seizures or who have seizures that spread quickly to all parts of the brain, surgical removal of the nerve fibers that connect the two sides of the brain can be helpful.
  • Examples of drugs for treating a seizure and epilepsy include carbamazepine, ethosuximide, gabapentin, lamotrignine, phenobarbital, phenytoin, primidone, valproic acid, trimethadione, bemzodiaepines, ⁇ -vinyl GABA, acetazolamide, and felbamate.
  • Anti-seizure drugs can have side effects such as drowsiness; hyperactivity; hallucinations; inability to concentrate; central and peripheral nervous system toxicity, such as nystagmus, ataxia, diplopia, and vertigo; gingival hyperplasia; gastrointestinal disturbances such as nausea, vomiting, epigastric pain, and anorexia; endocrine effects such as inhibition of antidiuretic hormone, hyperglycemia, glycosuria, osteomalacia; and hypersensitivity such as scarlatiniform rash, morbilliform rash, Stevens-Johnson syndrome, systemic lupus erythematosus, and hepatic necrosis; and hematological reactions such as red-cell aplasia, agranulocytosis, thrarnbocytopenia, aplastic anemia, and megaloblastic anemia.
  • the Merck Manual of Medical Information 345-350 R. Berkow ed., 1997).
  • a seizure is the result of abnormal electrical discharge in the brain.
  • the discharge can involve a small area of the brain and lead to the person only noticing an odd taste or smell or it can involve a large area of the brain and lead to convulsions, i.e., a seizure that causes jerking and spasms of the muscles throughout the body. Convulsions can also result in brief attacks of altered consciousness and loss of consciousness, muscle control, or bladder control.
  • a seizures is often preceded by auras, i.e., unusual sensations of smell, taste, or vision or an intense feeling that a seizure is about to begin.
  • a seizure typically lasts for about 2 to 5 minutes.
  • a stroke or cerebro vascular accident is the death of brain tissue (cerebral infarction) resulting from the lack of blood flow and insufficient oxygen to the brain.
  • a stroke can be either ischemic or hemorrhagic.
  • blood supply to the brain is cut off because of athersclerosis or a blood clot that has blocked a blood vessel, a hemorrhagic stroke, a blood vessel bursts preventing normal blood flow and allowing blood to leak into an area of the brain and destroying it. Most strokes develop rapidly and cause brain damage within minutes.
  • strokes can continue to worsen for several hours or days.
  • Symptoms of strokes vary depending on what part of the brain is effected. Symptoms include loss or abnormal sensations in an arm or leg or one side of the body, weakness or paralysis of an arm or leg or one side of the body, partial loss of vison or hearing, double vision, dizziness, slurred speech, difficulty in thinking of the appropriate word or saying it, inability to recognize parts of the body, unusual movements, loss of bladder control, imbalance, and falling, and fainting.
  • the symptoms can be permanent and can be associated with coma or stupor. Strokes can cause edema or swelling of the brain which can further damage brain tissue. For persons suffering from a stroke, intensive rehabilitation can help overcome the disability caused by impairment of brain tissue. Rehabilitation trains other parts of the brain to assume the tasks previously performed by the damaged part.
  • drugs for treating strokes include anticoagulants such as heparin, drugs that break up clots such as streptokinase or tissue plasminogen activator, and drugs that reduce swelling such as mannitol or corticosteroids.
  • anticoagulants such as heparin
  • drugs that break up clots such as streptokinase or tissue plasminogen activator
  • drugs that reduce swelling such as mannitol or corticosteroids.
  • Pruritus is an unpleasant sensation that prompts scratching. Pruritus can be attributed to dry skin, scabies, dermatitis, herpetiformis, atopic dermatitis, pruritus vulvae et ani, miliaria, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria, urticarial eruptions of pregnancy, psoriasis, lichen planus, lichen simplex chronicus, exfoliative dermatitis, folliculitis, bullous pemphigoid, and fiberglass dermatitis.
  • pruritus is treated by phototherapy with ultraviolet B or PUNA or with therapeutic agents such as naltrexone, nalmefene, danazol, tricyclics, and antidepressants.
  • mGluR5 metabotropic glutamate receptor 5
  • German patent application no 199 34 799 to Rainer et al. describes a chiral- smectic liquid crystal mixture containing compounds with 2 linked (hetero)aromatic rings or compounds with 3 linked (hetero)aromatic rings.
  • the present invention encompasses compounds having the formula (la):
  • R is -CI, -Br, -I, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • R 4 is -H or -(C r C 6 )alkyl
  • each R 6 is independently -( -C ⁇ alkyl, -(C 2 -C 6 )alkenyl, -(C 2 -C 6 )alkynyl,
  • R is -H, -halo, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • the present invention encompasses compounds having the formula (Ha):
  • R is -CI, -Br, -I, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • each R 7 is independently -H, -( -C ⁇ alkyl, -(C 2 -C 6 )alkenyl, -(C 2 -C 6 )alkynyl, -(C 3 -C 8 )cycloalkyl, -(C 5 -C 8 )cycloalkenyl, -phenyl, -(C 3 -C 5 )heterocycle, -C(hal
  • R 10 is -H or -(C r C 4 )alkyl; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is 0 or 1; and x is O or 1.
  • the present invention encompasses compounds having the formula (Ilia):
  • R is -CI, -Br, -I, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • each R 3 is independently: (a) -halo, -CN, -OH, -O(C r C 6 )alkyl, -NO 2 , or -NH 2 ;
  • each R 6 is independently -(C 1 -C 6 )alkyl, -(C 2 -C 6 )alkenyl, -(C 2 -C 6 )alkynyl, -(C 3 -C 8 )cycloalkyl, -(C 5 -C 8 )cycloalkenyl, -phenyl, -(C 3 -C 5 )heterocycle, -C(halo) 3 , -CH(halo) 2 , -CH 2 (halo), -CN, -OH, -halo, -N 3 , -NO 2 , -N(R 7 ) 2 , -CH
  • the present invention encompasses compounds having the formula (IJJb):
  • R is -H, -halo, -(C 1 -C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • each R 3 is independently:
  • each R 7 is independently -H, -( -C ⁇ alkyl, -(C 2 -C 6 )alkenyl, -(C 2 -C 6 )alkynyl, -(C 3 -C 8 )cycloalkyl, -(C 5 -C 8 )cycloalkenyl, -phenyl, -(C 3 -C 5 )heterocycle, -C(hal
  • the present invention also encompasses compounds having the formula (INa):
  • R j is -halo, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently: (a) -halo, -CN, -OH, -O(C r C 6 )alkyl, -NO 2 , or -NH 2 ;
  • Ri is -halo, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • R 3 is -CH 3 ;
  • R 8 and Rg are each independently -H, -(C j -C ⁇ alkyl, -(C 2 -C 6 )alkenyl, -(C 2 -C 6 )alkynyl, -(C 3 -C 8 )cycloalkyl, -(C 5 -C 8 )cycloalkenyl, -phenyl, -C(halo) 3 , -CH(halo) 2 , -CH 2 (halo), -OC(halo) 3 , -OCH(halo) 2 , -OCH 2 (halo), -CN, -OH, -halo, -N 3 , -N(R 7 ) 2 ,
  • each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; and x is O or 1.
  • N the formula (N):
  • R ! is -halo, -(C r C 6 )alkyl, -NO 2 , -CN, -OH, -OCH 3 , -NH 2 , -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo); each R 2 is independently:
  • a compound of formula (la), (lb), (Ha), (lib), (IHa), (mb), (INa), (INb), and (N) or a pharmaceutically acceptable salt thereof is useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, apruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal.
  • the invention also relates to compositions comprising an effective amount of a Benzoazolylpiperazine Compound and a pharmaceutically acceptable carrier or excipient.
  • the compositions are useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal.
  • the invention further relates to methods for treating pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound.
  • the invention further relates to methods for preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound.
  • the invention still further relates to methods for inhibiting Nanilloid Receptor
  • NR1 Benzoazolylpiperazine
  • the invention still further relates to methods for inhibiting mGluR5 function in a cell, comprising contacting a cell capable of expressing mGluR5 with an effective amount of a Benzoazolylpiperazine Compound.
  • the invention still further relates to methods for inhibiting metabotropic glutamate receptor 1 ("mGluRl") function in a cell, comprising contacting a cell capable of expressing mGluRl with an effective amount of a Benzoazolylpiperazine Compound.
  • mGluRl metabotropic glutamate receptor 1
  • the invention still further relates to a method for preparing a composition comprising the step of admixing a Benzoazolylpiperazine Compound and a pharmaceutically acceptable carrier or excipient.
  • the invention still further relates to a kit comprising a container containing an effective amount of a Benzoazolylpiperazine Compound.
  • the present invention still further relates to a compound selected from the group consisting of
  • the present invention still further relates to a compound selected from the group consisting of
  • the present invention still further relates to a compound selected from the group consisting of
  • a j is a pyridyl group, hi another embodiment, AT J is a pyrimidinyl group.
  • x is 1 and A is -C(O)-N(R 4 )-. In another embodiment, x is 1 and A is -C(S)-N(R 4 )-.
  • x is 0. In another embodiment, n or p is 0. In another embodiment, n or p is 1. In another embodiment, m is 0. In another embodiment, m is 1.
  • R 4 is -H. In another embodiment, R 4 is -(C r C 6 )alkyl.
  • AT J is a pyridyl group, x is 1, and A is -C(O)N(R 4 )-.
  • A is a pyridyl group, x is 1, and A is -C(S)N(R 4 )-.
  • Ar ⁇ is a pyrimidinyl group, x is 1, and A is -
  • Ax x is a pyrimidinyl group, x is 1, and A is -
  • R ⁇ is -CI.
  • Rj is -Br. hi another embodiment, R j is -I.
  • R is -(C,-C 6 )alkyl.
  • R j is -CH 3 .
  • R, is -NO 2 .
  • R ⁇ is -CN.
  • R ⁇ is -OH.
  • R x is -OCH 3 .
  • R x is -NH 2 .
  • R j is -C(halo) 3 .
  • R 1 is -CH(halo) 2 .
  • R x is -CH 2 (halo).
  • n and p are 1 and R 2 is -halo, -CN, -OH, -O(C C 6 )alkyl, -NO 2 , or -NH 2 .
  • n and p are 1 and R 2 is -(C r C 10 )alkyl, -(C 2 - C 10 )alkenyl, -(C 2 -C 10 )alkynyl, -(C 3 -C 10 )cycloalkyl, -(C 8 -C ⁇ 4 )bicycloalkyl, -(C 8 - C 14 )tricycloalkyl, -(C 5 -C 10 )cycloalkenyl,-(C 8 -C 14 )bicycloalkenyl, -(C 8 -C 14 )tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R 5 groups.
  • n and p are 1 and R 2 is -phenyl, -naphthyl, -(C 14 )aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups; h another embodiment, m is 1 and R 3 is -halo, -CN, -OH, -O ⁇ -C ⁇ aU l, -NO 2 , or -NH 2 .
  • m is 1 and R 3 is -(C r C 10 )alkyl, -(C 2 -C 10 )alkenyl, -(C 2 - C 10 )alkynyl, -(C 3 -C 10 )cycloalkyl, -(C 8 -C 14 )bicycloalkyl, -(C 8 -C 14 )tricycloalkyl, -(C 5 - C 10 )cycloalkenyl,-(C 8 -C 14 )bicycloalkenyl, -(C 8 -C 14 )tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R 5 groups.
  • m is 1 and R 3 is -phenyl, -naphthyl, -(C 14 )aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups.
  • R 8 and Re are each independently -H, -halo, -(C r C 6 )alkyl, -O(C r C 6 )alkyl, -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo).
  • At least one of R 8 and Rn is -H.
  • n, p, and m are 0; R ⁇ is -CI -Br, or, -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; and R 8 and Rg are -H.
  • n, p, and m are 0; Rj is -CI x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, and R 8 and Rg are -H.
  • n, p, and m are 0; R x is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -halo, hi another embodiment, Rj is -CI. hi another embodiment, Rg is -CI. another embodiment, Rg is -Br. In another embodiment,
  • n, p, and m are 0; R ⁇ is -CI x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and R g is -halo.
  • R ! is -CI.
  • Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1 ; A is
  • R 4 is -H; R 8 is -halo; and Rg is -H.
  • R is -CI.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • n, p, and m are 0; R t is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -halo, and Rg is -H.
  • R j is -CI.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • n, p, and m are 0; R x is -CI -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CH 3 .
  • n, p, and m are 0; R, is -CI x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CH 3 .
  • R j is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CH 3 ; and Rg is -H.
  • n, p, and m are 0; Ri is -C ⁇ x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CH 3 , and Rg is -H.
  • n, p, and m are 0; R, is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CF 3 .
  • n, p, and m are 0; R ⁇ is -CI.
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CF 3 .
  • n, p, and m are 0; R j is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CF 3 ; and Rg is -H.
  • n, p, and m are 0; R j is -CI.
  • x is 1; A is -C(O)-N(R 4 )-;
  • n, p, and m are 0; R x is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • n, p, and m are 0; R is -CI.
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • n, p, and m are 0; Rj is -CI -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • n, p, and m are 0; R ⁇ is -CI. x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H. In another embodiment, n, p, and m are 0; Rj is -CH 3 . x is 1 ; A is
  • n, p, and m are 0; R, is -CH 3 .
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • n, p, and m are 0;
  • R t is -CH 3 .
  • x is 1 ; A is
  • R 8 is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -halo; and Rg is -H. h another embodiment, R 8 is -CI. In another embodiment, R 8 is -Br. In another embodiment, R 8 is -F.
  • n, p, and m are 0; R is -CH 3 . x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CH 3 .
  • n, p, and m are 0; R l is -CH 3 . x is 1 ; A is
  • n, p, and m are 0; R, is -CH 3 .
  • x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CF 3 .
  • n, p, and m are 0; Rj is -CH 3 . x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CF 3 ; and Rg is -H.
  • n, p, and m are 0; Rj is -CH 3 . x is 1 ; A is
  • R 4 is -H
  • R 8 is -H
  • Rg is -OCH 2 CH 3 .
  • n, p, and m are 0; Rj is -CF 3 .
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; and R 8 and Rg are -H.
  • n, p, and m are 0; Rj is -CF 3 .
  • x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • n, p, and m are 0; R j is -CF 3 .
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -halo; and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. In another embodiment, R 8 is -F. hi another embodiment, n, p, and m are 0; R j is -CF 3 . x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CH 3 .
  • n, p, and m are 0; R ⁇ is -CF 3 .
  • x is 1 ;
  • A is -C(O)-N(R 4 )-;
  • R 4 is -H;
  • R 8 is -H; and
  • Rg is -CF 3 .
  • n, p, and m are 0;
  • R x is -CF 3 .
  • x is 1;
  • A is -C(O)-N(R 4 )-;
  • R 4 is -H;
  • R 8 is -CF 3 ; and
  • Rg is -H.
  • n, p, and m are 0;
  • R j is -CF 3 .
  • x is 1 ;
  • A is
  • n, p, and m are 0; R x is -CF 3 . x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -OCH 2 CH 3 ; and R g is -H.
  • n, p, and m are 0; R, is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -tert-butyl; and R g is -H.
  • n, p, and m are 0; R ⁇ is -CI.
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -tert-butyl; and Rg is -H.
  • n, p, and m are 0; R l is R, is -CI -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • n, p, and m are 0; R t is Rj is -CI.
  • x is 1; A is -C(O)-
  • R 4 is -H
  • R 8 is -H
  • Rg is -tert-butyl
  • n, p, and m are 0; R t is -CH 3 ; x is 1; A is -C(O)- N(R 4 )-; R 4 is -H; R 8 is -tert-butyl; and Rg is -H.
  • n, p, and m are 0; R, is -CH 3 ; x is 1; A is -C(O)- N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • n, p, and m are 0; R j is -CH 3 ; x is 1; A is -C(O)- N(R 4 )-; R 4 is -H; R 8 is -CH 3 ; and Rg is -CH 3 .
  • n is 0, Ax x is -2-(3-nitropyridyl)-, m is 0, x is 0, and R 8 and Rg are -H. In another embodiment, n is 0, Ax, is -2-(3-chloropyridyl)-, x is 1, A is -C(S)-
  • N(R 4 )-, m is 1, R 3 is -CH 3 , R 3 is attached to the carbon atom adjacent to the nitrogen attached to the -C(SO)-N(R 4 )- group, the carbon atom to which the R 3 group is attached has the R configuration, R 8 is -H, and Rg is -CH 3 .
  • n and p are 0; m is 1; R t is -CI, -Br, or -I.
  • x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; and R 8 and Rg are -H.
  • n and p are 0, m is 1, R t is -Cl ; x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R ⁇ is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -halo.
  • R g is -CI.
  • R g is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CI x is 1, A is -C(O)-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -H
  • Rg is -halo.
  • Rg is -CI.
  • R g is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -halo; and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F. hi another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CI , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • h another embodiment, R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R 1 is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -Cl ; x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CI x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CI x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -CF 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CI , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R x is -CI, -Br, or -I. x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R x is -CI, x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R x is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment the carbon atom to which the R 3 group is attached has the S configuration
  • n and p are 0, m is 1, Rj is -CI, x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -OCH 2 CH 3
  • Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Rg is -halo.
  • Rg is -CI.
  • R, is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CH 3 , x is 1, A is -C(O)-
  • N(R 4 )-, R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -H
  • Rg is -CH 3
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 1, A is -C(O)-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -CH 3
  • Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1
  • R j is -CH 3
  • x is 1
  • A is -C(O)-
  • N(R 4 )-, R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -H
  • Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ ⁇ is -CH 3 , x is 1, A is -C(O)-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -CF 3
  • Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R x is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, hi another embodiment Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R x is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R r is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CF 3 , x is 1, A is -C(O)- N(R )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R, is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -tert-butyl; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment the carbon atom to which the R 3 group is attached has the S configuration
  • hi another embodiment n and p are 0, m is 1, Rj is -CI, x is 1, A is -C(O)- N(R 4 )-
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 4 is -H
  • R 8 is -tert-butyl
  • Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and R ⁇ is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R : is -CI, x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n, p, and m are 0; R, is -CI, -Br, or, -I; x is 0; R 4 is -H;
  • n, p, and m are 0; Ri is -CI. x is 0; R 4 is -H; and R 8 and Rg are -H.
  • n, p, and m are 0; R t is -CI, -Br, or, -I; x is 0; R 4 is -H;
  • R 8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F.
  • n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H; and R g is -halo.
  • Rg is -CI.
  • Rg is -Br. hi another embodiment, Rg is -F.
  • n, p, and m are 0; R, is -CI, -Br, or, -I.
  • x is 0; R 4 is -H; R 8 is -halo; and Rg is -H.
  • R 8 is -CI. hi another embodiment, R 8 is -Br. In another embodiment, R 8 is -F.
  • n, p, and m are 0; R : is -CI; x is 0; R 4 is -H; R 8 is - halo; and Rg is -H. h another embodiment, R 8 is -CI. hi another embodiment, R 8 is -Br. h another embodiment, R 8 is -F.
  • n, p, and m are 0; R, is -CI, -Br, or, -I.
  • x is 0; R 4 is -H; hi another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H; h another embodiment, n, p, and m are 0; R x is -CI, -Br, or, -I; x is 0; R 4 is -H;
  • n, p, and m are 0; R, is -CI; x is 0; R 4 is -H; R 8 is In another embodiment, n, p, and m are 0; R, is -CI, -Br, or, -I; x is 0; R 4 is -H; In another embodiment, n, p, and m are 0; R, is -CI; x is 0; R 4 is -H; R 8 is -H; hi another embodiment, n, p, and m are 0; R j is -CI, -Br, or, -I; x is 0; R is -H; In another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is
  • n, p, and m are 0; R j is -CI, -Br, or, -I; x is 0; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H;
  • n, p, and m are 0; R ⁇ is -CI, -Br, or, -I; x is 0; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • n, p, and m are 0; R t is -CI; x is 0; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • R ⁇ is -CH 3 ; x is 0; R 4 is -H; and R 8 hi another embodiment, n, p, and m are 0; R, is -CH 3 ; x is 0; R 4 is -H; R 8 is -H; and Rg is -halo.
  • Rg is -CI. i another embodiment, Rg is -Br.
  • Rg is -F.
  • n, p, and m are 0; R, is -CH 3 ; x is 0; R 4 is -H; R 8 is
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • hi another embodiment, n, p, and m are 0; R j is -CH 3 ; x is 0; R 4 is -H; R 8 is In another embodiment, n, p, and m are 0; R ⁇ is -CH 3 ; x is 0; R 4 is -H; R 8 is hi another embodiment, n, p, and m are 0; R j is -CH 3 ; x is 0; R 4 is -H; R 8 is
  • n, p, and m are 0; R ! is -CH 3 ; x is 0; R 4 is -H; R 8 is -CF 3 ; andRg is -H.
  • n, p, and m are 0; R j is -CH 3 ; x is 0; R 4 is -H; R 8 is -Hj and R g is -OCH j CH,.
  • n, p, and m are 0, R t is -CH 3 ; x is 0; R 4 is -H; R 8 is
  • n, p, and m are 0; R ⁇ is -CF 3 ; x is 0; R 4 is -H; and R 8
  • n, p, and m are 0; R j is -CF 3 ; x is 0; R 4 is -H; R 8 is -H; and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br. hi another embodiment, Rg is -F.
  • n, p, and m are 0; R l is -CF 3 ; x is 0; R 4 is -H; R 8 is -halo; and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. h another embodiment, R 8 is -F.
  • n, p, and m are 0, R j is -CF 3 ; x is 0; R 4 is -H; R 8 is -H; hi another embodiment, n, p, and m are 0; R, is -CF 3 ; x is 0; R 4 is -H; R 8 is
  • n, p, and m are 0; R x is -CF 3 ; x is 0; R 4 is -H; R 8 is -H; hi another embodiment, n, p, and m are 0; R is -CF 3 ; x is 0; R 4 is -H; R 8 is hi another embodiment, n, p, and m are 0; R j is -CF 3 ; x is 0; R 4 is -H; R 8 is -H;
  • n, p, and m are 0; R ⁇ ⁇ is -CF 3 ; x is 0; R 4 is -H; R 8 is
  • n, p, and m are 0; R j is -CI, -Br, or, -I; x is 0; R 4 is -H; R 8 is -tert-butyl; and R g is -H.
  • n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -tert- butyl; and Rg is -H.
  • n, p, and m are 0; R j is -CI, -Br, or, -I; x is 0; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • n, p, and m are 0; R t is -CI; x is 0; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • n, p, and m are 0; R ⁇ is -CH 3 ; x is 0; R 4 is -H; R 8 is -tert-butyl; and Rg is -H.
  • n, p, and m are 0; R ⁇ is -CH 3 ; x is 0; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • n, p, and m are 0; Rj is -CH 3 ; x is 0; R 4 is -H; R 8 is
  • n and p are 0; m is 1 ; R ! is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; R ⁇ is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 8 is -H; and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br. hi another embodiment, Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R ! is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 8 is -halo; and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R x is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -halo, and R, is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R ⁇ is -CI, -Br, or -I; x is 0; R 4 is
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group;
  • R 8 is -H; and
  • Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • n and p are 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • n and p are 0; m is 1 ; R j is -CI, -Br, or -I; x is 0; R 4 is
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group;
  • R 8 is -CH 3 ; and
  • Rg is -H.
  • n and p are 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R ⁇ is -CI, -Br, or -I; x is 0; R 4 is
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group;
  • R 8 is -H; and
  • Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 8 is -CF 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R 1 is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Ri is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R x is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • h another embodiment, R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CH 3 , x is 0, R 4 is -H, R 3 is
  • R 8 is -H
  • Rg is -CH 3
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CH 3 , x is 0, R 4 is -H, R 3 is
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R x is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -OCH 2 CH 3 , and R, is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -halo.
  • Rg is -CI.
  • R g is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • R 8 is -H
  • Rg is -CH 3
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CF 3 , x is 0, R 4 is -H, R 3 is
  • R 8 is -CH 3
  • Rg is -H
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CF 3 , x is 0, R 4 is -H, R 3 is
  • R 8 is -H
  • Rg is -CF 3
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is
  • R 8 is -CF 3
  • Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CF 3 , x is 0, R 4 is -H, R 3 is
  • R 8 is -H
  • Rg is -OCH 2 CH 3
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Ri is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R r is -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 4 is -H; R 8 is -tert-butyl; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ⁇ is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R t is -CI, -Br, or, -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R ! is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R g is -H, and R g is -tert-butyl.
  • R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R t is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • AT J is a pyridyl group, n is 0; m is 1; Rj is -CH 3 , -CI,
  • x is 1;
  • A is -C(O)-N(R 4 )-;
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group;
  • R 4 is -H;
  • R 8 is -H; and
  • Rg is -halo.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • A is a pyridyl group, n is 0, m is 1, R 1 is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyridyl group; n is 0; m is 1; R j is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • A is a pyridyl group, n is 0, m is 1, R, is -CI, x is 1,
  • A is -C(O)-N(R 4 )-
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br.
  • Ax l is a pyridyl group
  • n is 0, m is 1, R, is -CH 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • A is a pyrimidinyl group; p is 0; m is 1; R t is -CH 3 , -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and Rg is - halo, h another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a x is a pyrimidinyl group, p is 0, m is 1, R ! is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • A is a pyrimidinyl group; p is 0; m is 1; R ⁇ is -CI,
  • x is 1;
  • A is -C(O)-N(R 4 )-;
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group;
  • R 4 is -H;
  • R 8 is -H; and
  • Rg is -Br.
  • AT J is a pyrimidinyl group
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and R, is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • A is a pyrimidinyl group, p is 0, m is 1, R x is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax ⁇ is a pyridyl group; n is 0; m is 1; R ⁇ is -CH 3 , -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 4 is -H; R 8 is -H; and Rg is -halo, hi another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar t is a pyridyl group
  • n is 0, m is 1
  • R x is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax x is a pyridyl group; n is 0; m is 1; R ⁇ is -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 4 is -H; R 8 is -H; and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyridyl group
  • n is 0, m is 1, R t is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax ⁇ is a pyridyl group
  • n is 0, m is 1
  • R t is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax x is a pyrimidinyl group; p is 0; m is 1; R l is -CH 3 , -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 4 is -H; R 8 is -H; and Rg is -halo.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyrimidinyl group
  • p is 0, m is 1
  • Rj is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyrimidinyl group; p is 0; m is 1; R t is -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R 4 is -H; R 8 is -H; and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar t is a pyrimidinyl group
  • p is 0, m is 1, R, is -CI, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • AT J is a pyrimidinyl group
  • p is 0, m is 1, R, is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and R, is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -(C C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R 3 group is attached is in the R configuration. In another embodiment, m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group.
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • the present invention also encompasses compounds of formula (lb):
  • Ax x , R 3 , R 8 , Rg, A, x, and m are defined above for the Benzoazolylpiperazine Compounds of formula (lb), hi one embodiment, Ax, is a pyrazinyl group. In another embodiment, A ⁇ is a pyridazinyl group. In another embodiment, Ar t is a thiazanyl group. In another embodiment, x is 1 and A is -C(O)-N(R 4 )-. hi another embodiment, x is 1 and A is -C(S)-N(R 4 )-. hi another embodiment x is 0.
  • p is 0.
  • p is 1. hi another embodiment, m is 0.
  • n 1
  • R 4 is -H.
  • R 4 is -(C r C 6 )alkyl.
  • Ax is a pyrazinyl group, x is 1, and A is -C(O)N(R 4 )-
  • AT J is a pyrazinyl group
  • x is 1
  • A is -C(S)N(R 4 )-
  • AT J is a pyridazinyl group
  • x is 1
  • A is -
  • Ax is a pyridazinyl group, x is 1, and A is - C(S)N(R 4 )-,
  • Ax is a thiazanyl group, x is 1, and A is -C(O)N(R 4 )-
  • Ax is a thiazanyl group, x is 1, and A is -C(S)N(R 4 )-.
  • R l is -H.
  • R j is -CI.
  • R ⁇ is -Br.
  • R x is -I.
  • Ri is -F.
  • R x is -(C j -C ⁇ alkyl.
  • R t is -CH 3 .
  • R ⁇ is -NO 2 .
  • R is -CN.
  • R is -OH.
  • R is -OCH 3 .
  • R is -NH 2 .
  • R j is -C(halo) 3 .
  • R j is -CH(halo) 2 .
  • R is -CH 2 (halo).
  • p is 1 and R 2 is -halo, -CN, -OH, -NO 2 , or -NH 2 .
  • R 2 is -(C C 10 )alkyl, -(C 2 -C 10 )alkenyl, -(C 2 - C 10 )alkynyl, -(C 3 -C 10 )cycloalkyl, -(C 8 -C 14 )bicycloalkyl, -(C 8 -C 14 )tricycloalkyl, -(C 5 - C 10 )cycloalkenyl,-(C 8 -C 14 )bicycloalkenyl, -(C 8 -C 14 )tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R 5 groups.
  • p is 1 and R 2 is -phenyl, -naphthyl, -(C 14 )aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups.
  • m is 1 and R 3 is -halo, -CN, -OH, -O(C r C 6 )alkyl,
  • m is 1 and R 3 is -(C ⁇ -C 10 )alkyl, -(C 2 -C 10 )alkenyl, -(C 2 - C 10 )alkynyl, -(C 3 -C 10 )cycloalkyl, -(C 8 -C 14 )bicycloalkyl, -(C 5 - C 10 )cycloalkenyl,-(C 8 -C 14 )bicycloalkenyl, -(C 8 -C 14 )tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R 5 groups.
  • m is 1 and R 3 is -phenyl, -naphthyl, -(C 14 )aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups.
  • R 8 and Rg are each independently -H, halo, -(C r
  • At least one of R 8 or Rg is -H.
  • R is -halo
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 and Rg are -H
  • p and m are 0, R, is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 and Rg are -H.
  • R x is -halo
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • R is -halo
  • g is -CI.
  • Rg is -Br.
  • R g is -F.
  • p and m are 0, R x is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and R g is -halo, hi another embodiment, Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • p and m are 0, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -halo, and R g is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • p and m are 0, R x is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. hi another embodiment, R 8 is -F. In another embodiment, p and m are 0, R j is -halo, x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H
  • R 8 is -H
  • Rg is -CH 3 .
  • R ⁇ is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -CH 3 .
  • R is -halo x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -H.
  • R j is -CI x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -H.
  • R ⁇ is -halo x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 .
  • p and m are 0, R ⁇ is -CI x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 .
  • p and m are 0, R j is -halo x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and Rg is -H.
  • R is -CI x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CF 3
  • Rg is -H.
  • R ⁇ is -halo
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -OCH 2 CH 3 .
  • R j is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • g is -OCH 2 CH 3
  • p and m are 0, ⁇ is -halo
  • x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H, R 8 is -OCH 2 CH 3 , and R g is -H.
  • R j is -CI x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • p and m are 0, R t is -CH 3 x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, and R 8 and Rg are -H.
  • p and m are 0, R ⁇ is -CH 3 x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H, R 8 is -H, and R g is -halo.
  • Rg is -CI.
  • R g is -Br.
  • R g is -F.
  • p and m are 0, R j is -CH 3 x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. hi another embodiment, R 8 is -F.
  • R j is -CH 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • R ⁇ is -CH 3 .
  • R ⁇ is -CH 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -H.
  • R ! is -CH 3 x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H
  • R 8 is -H
  • R, is -CF 3 .
  • R j is -CH 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CF 3
  • Rg is -H.
  • R j is -CH 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -OCH 2 CH 3 .
  • R x is -CH 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -OCH 2 CH 3
  • Rg is -H.
  • R j is -CF 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 and Rg are -H
  • p and m are 0,
  • R x is -CF 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -halo.
  • Rg is -CI.
  • Rg is -Br. hi another embodiment, Rg is -F.
  • R l is -CF 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -halo
  • Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • p and m are 0, R j is -CF 3, x is 1, A is -C(O)-N(R 4 )-, R 4 s -H, R 8 is -H, and Rg is -CH 3 .
  • R ⁇ is -CF 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -H
  • p and m are 0, R, is -CF 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -CF 3
  • p and m are 0, R, is -CF 3 x is 1, A is -C(O)-N(R 4 )-, R 4 is -H
  • R 8 is -CF 3
  • Rg is -H.
  • R ⁇ is -CF 3 x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -OCH 2 CH 3 .
  • R j is -CF 3 x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -tert-butyl, and R, is -H.
  • p and m are 0, R, is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • R j is -halo
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -tert-butyl
  • p and m are 0, R 1 is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -tert-butyl.
  • R x is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • R j is -CH 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -tert-butyl.
  • p and m are 0, R j is -CH 3
  • x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -CH 3 .
  • p is 0, m is 1, R, is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, hi another embodiment, Rg is -CI. In another embodiment, Rg is -Br. hi another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R is -halo, x is 1, A is -C(O)-N(R )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R t is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R t is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R g is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R t is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, hi another embodiment R, is -CI.
  • Rg is -Br.
  • hi another embodiment, Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Rg is -halo.
  • Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. hi another embodiment, R 8 is -F. hi another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R r is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and R g is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R is -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and R g is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • R x is -halo x is 0, R 4 is -H, and R 8 and
  • p and m are 0, R ⁇ is -CI x is 0, R 4 is -H, and R 8 and Rg are -H.
  • Rg is -halo, hi another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F.
  • R j is -halo
  • x is 0,
  • R 4 is -H
  • R 8 is -halo
  • Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • R x is -CI
  • x is 0,
  • R 4 is -H
  • R 8 is -halo
  • Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • p and m are 0, R is -halo, x is 0, R 4 is -H, R 8 is -H,
  • p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -H, and
  • R x is -halo
  • x is 0, R 4 is -H
  • R 8 is -CH 3
  • p and m are 0, R j is -CI
  • x is 0, R 4 is -H
  • R 8 is -CH 3
  • p and m are 0, R j is -halo
  • x is 0, R 4 is -H
  • R 8 is -H
  • R g is -CF 3 .
  • p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -H, and In another embodiment, p and m are 0, R, is -halo, x is 0, R 4 is -H, R 8 is -CF 3 ,
  • p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -CF 3 ,
  • R j is -halo
  • x is 0, R 4 is -H, R 8 is -H, and R g is -OCH 2 CH 3 .
  • p and m are 0, R, is -CI
  • x is 0, R 4 is -H, R 8 is -H
  • p and m are 0, R, is -halo
  • x is 0, R 4 is -H, R 8 is In another embodiment, p and m are 0, Rj is -CI, x is 0, R 4 is -H, R 8 is
  • p and m are 0, R, is -CH 3 , x is 0, R 4 is -H, and R 8 and
  • R j is -CH 3
  • x is 0,
  • R 4 is -H
  • R 8 is -H
  • Rg is -halo
  • Rg is -Br.
  • h another embodiment, Rg is -F.
  • p and m are 0, R, is -CH 3 , x is 0, R 4 is -H, R 8 is -halo, and Rg is -H. h another embodiment, R 8 is -CI. In another embodiment, R 8 is -Br. In another embodiment, R 8 is -F. In another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -H,
  • p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -CH 3 ,
  • R x is -CH 3 , x is 0, R 4 is -H, R 8 is -H, hi another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -CF 3 , hi another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -H, and R g is -OCH 2 CH 3 .
  • p and m are 0, R x is -CH 3 , x is 0, R 4 is -H, R 8 is -H, R 8 is
  • R ! is -CF 3
  • x is 0,
  • R 4 is -H
  • R x is -CF 3 , x is 0, R 4 is -H, R 8 is -H, and R g is -halo.
  • Rg is -CI.
  • R, is -Br.
  • Rg is -F.
  • p and m are 0, R, is -CF 3 , x is 0, R 4 is -H, R 8 is -halo, and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br.
  • R 8 is -F.
  • p and m are 0, R, is -CF 3 , x is 0, R 4 is -H, R 8 is -CH 3 ,
  • p and m are 0, R x is -CF 3 , x is 0, R 4 is -H, R 8 is -H, hi another embodiment, p and m are 0, R, is -CF 3 , x is 0, R 4 is -H, R 8 is -CF 3 ,
  • R x is -CF 3
  • x is 0,
  • R 4 is -H
  • R 8 is -H
  • p and m are 0,
  • R t is -CF 3
  • x is 0,
  • R 4 is -H
  • R 8 is
  • p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -CH 3 , ha another embodiment, p is 0, m is 1, R x is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R 8 and Rg are -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -halo.
  • Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, R g is -F. In another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI.
  • Rg is -Br. ha another embodiment, R g is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ] is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. h another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. In another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R t is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CI, x is 0, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R, is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R t is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R ⁇ is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R ⁇ is -CI, x is 0, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI. ha another embodiment, R 8 is -Br.
  • R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R g is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R t is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, Rg is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R 8 and R g are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and R g is -halo. In another embodiment Rg is -CI. In another embodiment,
  • Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -halo, and Rg is -H. ha another embodiment R 8 is -CI.
  • m is 1
  • R is -CF 3
  • x is 1
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 8 is -halo
  • Rg is -H. ha another embodiment R 8 is -CI.
  • R 8 is -Br. In one embodiment, R 8 is -F. a another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, R ⁇ is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -CH 3 . ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R x is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and R g is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R l is -CF 3 , x is 0, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -tert-butyl, and R ⁇ is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R ⁇ is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, Rg is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R ⁇ is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 . ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a pyrazinyl group, p is 0, m is 1, R x is -CH 3 or -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -halo, h another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • AT J is a pyrazinyl group
  • p is 0, m is 1, R ⁇ is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar ! is a pyrazinyl group
  • p is 0, m is 1, R ⁇ is -halo, x is 1,
  • A is -C(O)-N(R 4 )-
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax x is a pyrazinyl group, p is 0, m is 1, Ri is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R g is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax ⁇ is a pyrazinyl group, p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar ! is a pyridazinyl group
  • p is 0, m is 1, R j is -CH 3 or -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a x is a pyridazinyl group, p is 0, m is 1, Ri is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and R g is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • AT ] is a pyridazinyl group
  • p is 0, m is 1, R ! is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a pyridazinyl group
  • p is 0, m is 1, R ! is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar ! is a thiazanyl group
  • p is 0, m is 1, R x is -CH 3 or -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -halo, h another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a thiazanyl group, p is 0, m is 1, Ri is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax x is a thiazanyl group, p is 0, m is 1, R l is -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a thiazanyl group, p is 0, m is 1, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a thiazanyl group
  • p is 0, m is 1, R ⁇ is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyrazinyl group, p is 0, m is 1, Rj is -CH 3 or -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyrazinyl group
  • p is 0, m is 1
  • R is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyrazinyl group
  • p is 0, m is 1, Rj is -halo, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyrazinyl group
  • p is 0, m is 1,
  • Rj is -CI
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax ⁇ is a pyrazinyl group
  • p is 0, m is 1
  • Ri is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • A-Ci is a pyridazinyl group
  • p is 0, m is 1, R l is -CH 3 or -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a pyridazinyl group, p is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a pyridazinyl group
  • p is 0, m is 1, R !
  • R 3 is -halo
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group,
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar t is a pyridazinyl group
  • p is 0, m is 1
  • R j is -CI
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a pyridazinyl group
  • p is 0, m is 1
  • Ri is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ax is a thiazanyl group
  • p is 0, m is 1, Rj is -CH 3 or -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a thiazanyl group
  • p is 0, m is 1
  • Rj is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a thiazanyl group
  • p is 0, m is 1, Rj is -halo, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • R is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • a ⁇ is a thiazanyl group
  • p is 0, m is 1, Rj is -CI, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • AT J is a thiazanyl group
  • p is 0, m is 1, R, is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • m is 1 and R 3 is -(C 1 -C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0. ha another embodiment, m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -(C 1 -C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or a thiazanyl group
  • m is 1 and R 3 is -(C 1 -C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or a thiazanyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group
  • m is 1 and R 3 is -(C r C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • the present invention also encompasses compounds of formula (ha):
  • Ar is a pyrimidinyl group.
  • ha another embodiment, A ⁇ is a pyrazinyl group.
  • ha another embodiment, n or p is 0. ha another embodiment, n or p is 1.
  • ha another embodiment, m is 0. ha another embodiment, m is 1.
  • R 10 is -H. ha another embodiment, R 10 is -(C r C 4 )alkyl. ha another embodiment, R 10 is -CH 3 . ha another embodiment, R, is -CI. ha another embodiment, R x is -Br.
  • R ⁇ is -I. ha another embodiment, R ⁇ is -( -C ⁇ alkyl. ha another embodiment, R, is -CH 3 . ha another embodiment, R x is -NO 2 . ha another embodiment, R j is -CN.
  • R is -OH. ha another embodiment, R, is -OCH 3 . ha another embodiment, R j is -NH 2 . In another embodiment, R x is -C(halo) 3 . ha another embodiment, R j is -CH(halo) 2 . ha another embodiment, R j is -CH 2 (halo).
  • n and p are 1 and R 2 is -halo, -CN, -OH, -O(C r C 6 )alkyl, -NO 2 , or -NH 2 .
  • n and p are 1 and R 2 is -(C 1 -C 10 )alkyl, -(C 2 -
  • n and p are 1 and R 2 is -phenyl, -naphthyl, -(C 14 )aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups; ha another embodiment, m is 1 and R 3 is -halo, -CN, -OH, -O(C ⁇ -C 6 )alkyl, -NO 2 , or -NH 2 . ha another embodiment, m is 1 and R 3 is -(C,-C 10 )alkyl, -(C 2 -C 10 )alkenyl, -(C 2 -
  • m is 1 and R 3 is -phenyl, -naphthyl, -(C 14 )aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups.
  • R g and Rg are each independently -H, halo, -(C r C 6 )alkyl, -O(C r C 6 )alkyl, -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo).
  • R 8 or R is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R 4 is -H; and R 8 ha another embodiment, n, p, and m are 0; R, is -CI.
  • R 4 is -H; and R 8 and Rg are -H. ha another embodiment, n, p, and m are 0; R x is -CI -Br, or -I; R 4 is -H; R 8 is - halo H; and Rg is -H. ha another embodiment, Rg is -CI. a another embodiment, Rg is -Br. In another embodiment, Rg is -F.
  • n, p, and m are 0; Rj is -CI; R 4 is -H; R 8 is -halo; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; R x is -CI , -Br, or -I; R 4 is -H; R 8 is - H; and Rg is -CH 3 .
  • Rg is -CI. ha another embodiment, Rg is -Br. a another embodiment, Rg is -F.
  • n, p, and m are 0; R y is -CI.
  • R 4 is -H; R 8 is -H; and Rg is -CH 3 .
  • Rg is -Br.
  • Rg is -F. ha another embodiment, n, p, and m are 0; R r is -CI -Br, or -I; R 4 is -H; R 8 is -CH 3 ; and Rg is -H.
  • Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F.
  • ha another embodiment, n, p, and m are 0; R t is -CI. R 4 is -H; R 8 is -CH 3 ; and Rg is -H. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; R t is -CI, -Br, or -I; R 4 is -H; R 8 is - H; and Rg is -CF 3 . In another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F.
  • ha another embodiment, n, p, and m are 0; R j is -CI; R 4 is -H; R 8 is -H; and Rg is -CF 3 .
  • Rg is -CI.
  • Rg is -Br. ha another embodiment, Rg is -F.
  • n, p, and m are 0;
  • R j is -CI, -Br, or -I;
  • R 4 is -H;
  • R 8 is -CF 3 ; and R g is -H.
  • ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F.
  • ha another embodiment, n, p, and m are 0; R l is -CI; R 4 is -H; R 8 is -CF 3 ; and R g is -H. ha another embodiment, R g is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. a another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R 4 is -H; R 8 is
  • Rg is -CI.
  • Rg is - Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 . ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F.
  • ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is - Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F.
  • ha another embodiment, n, p, and m are 0; R j is -CI, Br, or -I; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; Rj is -CI; R 4 is -H; R 8 is -H; and Rg is -CF 3 . ha another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; Rj is -CI; R 4 is -H; R 8 is -CF 3 ; and
  • n, p, and m are 0; Rj is -CI, Br, or -I; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; R j is -CI; R 4 is -H; R 8 is -OCH 2 CH 3 ; ha another embodiment, n, p, and m are 0, Rj is -CH 3 , R 4 is -H, and R 8 and Rg are -H.
  • ha another embodiment, n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F.
  • n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -halo; and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. ha another embodiment, R 8 is -F.
  • n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -H; and ha another embodiment, n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -CH 3 ; and
  • n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -H; and ha another embodiment, n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -CF 3 ; and In another embodiment, n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -H; and ha another embodiment, n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; Rj is -CF 3 ; R 4 is -H; and R 8 and Rg are -H.
  • ha another embodiment, n, p, and m are 0; R j is -CF 3 ; R 4 is -H; R 8 is -H; and R g is -halo, ha another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CF 3 ; R 4 is -H; R 8 is -halo; and
  • R g is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F.
  • n, p, and m are 0; R t is -CF 3 ; R 4 is -H; R 8 is -H; and ha another embodiment, n, p, and m are 0; R j is -CF 3 ; R 4 is -H; R 8 is -CH 3 ; and
  • n, p, and m are 0; Rj is -CF 3 ; R 4 is -H; R 8 is -H; and hi another embodiment, n, p, and m are 0; R j is -CF 3 ; R 4 is -H; R 8 is -CF 3 ; and
  • n, p, and m are 0; R j is -CF 3 ; R 4 is -H; R 8 is -H; and ha another embodiment, n, p, and m are 0; R j is -CF 3 ; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; R 4 is -H; R 8 is
  • Rg is -H.
  • ha another embodiment, n, p, and m are 0; R j is -CI; R 4 is -H; R 8 is -tert-butyl; ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • n, p, and m are 0;
  • R j is -CI; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • ha another embodiment, n, p, and m are 0; R j is -CH 3 ; R 4 is -H; R 8 is -tert- butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; R x is -CH 3 ; R 4 is -H; R 8 is -H; and
  • n is 0, Ar j is -2-(3-chloropyridyl)-, m is 1, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, the carbon atom to which the R 3 group is attached has the R configuration, R 10 is -H, R 8 is ⁇ o-propyl, and R, is methyl.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; and R 8 and Rg are -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0; m is 1; R j is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R 8 is -H; and Rg is -halo, ha another embodiment R g is -CI. hi another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -H; and R g is -halo, h another embodiment Rg is -CI. ha another embodiment, R g is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -halo; and Rg is -H. ha another embodiment R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -halo; and Rg is -H. ha another embodiment R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration. .
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -H; and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R 8 is -H; and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R is -C1,;R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R 8 is -CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R 8 is -H; and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -H; and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0; m is 1; Rj is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -CF 3 ; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; R, is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -CF 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the - benzoimidazole group; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -benzoimidazole group; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 8 is -OCH 2 CH 3 ; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -halo, and Rg is -H. ha another embodiment R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R g is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, R j is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. ha another embodiment, n and p are 0, m is 1, R, is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -H, and R, is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -OCH 2 CH 3 , and R, is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -halo, i another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CF 3 , R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R 4 is -H; R 8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R, is -CI, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CI, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridyl group; n is 0; m is 1; Rj is -CH 3 , -CI, -Br, or -I; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyridyl group n is 0, m is 1, Rj is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyridyl group, n is 0, m is 1, Rj is -CI, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridyl group, n is 0, m is 1, Rj is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyrimidinyl group; p is 0; m is 1; R j is -CH 3 , -CI, -Br, or -I; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyrimidinyl group, p is 0, m is 1, R j is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyrimidinyl group; p is 0; m is 1; Rj is -CI, -Br, or -I; R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R 4 is -H; R 8 is -H; and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyrimidinyl group, p is 0, m is 1, R, is -CI, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyrimidinyl group
  • p is 0, m is 1,
  • Rj is -CH 3
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyrazinyl group; p is 0; m is 1; Rj is -CH 3 , -CI, -Br, or -I; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R 4 is -H; R 8 is -H; and R, is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CH 3 , R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyrazinyl group; p is 0; m is 1; Rj is -CI, -Br, or -I; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R 4 is -H; R 8 is -H; and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyrazinyl group, p is 0, m is 1, Rj is -CI, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyrazinyl group
  • p is 0, m is 1,
  • Rj is -CH 3
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • ha another embodiment, m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • ha another embodiment, m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- or the benzothiazolyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group and the carbon to which the R 3 group is attached is in the R configuration
  • ha another embodiment, m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group and the carbon to which the R 3 group is attached is in the S configuration
  • ha another embodiment, m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group
  • Arj, R 3 , R 8 , Rg, A, x, and m are defined above for the Benzoazolylpiperazine Compounds of formula (fib).
  • Arj is a pyridazinyl group.
  • Ar j is a thiazanyl group.
  • ha another embodiment, x is 1 and A is -C(O)-N(R 4 )-.
  • ha another embodiment, x is 1 and A is -C(S)-N(R 4 )-.
  • ha another embodiment x is 0. ha another embodiment, x is 1. ha another embodiment p is 0. ha another embodiment, p is 1. ha another embodiment m is 0. ha another embodiment, m is 1. ha another embodiment, R 4 is -H. ha another embodiment, R 4 is -(Cj-C 6 )alkyl.
  • R 10 is -H.
  • R 10 is -(C j -C 4 )alkyl. ha another embodiment, Rj 0 is -CH 3 . ha another embodiment, Arj is a pyrazinyl group, x is 1, and A is -C(O)N(R 4 )-. In another embodiment, Arj is a pyrazinyl group, x is 1, and A is -C(S)N(R 4 )-. hi another embodiment, Ar, is a thiazanyl group, x is 1, and A is -C(O)N(R 4 )-. ha another embodiment, Ar j is a thiazanyl group, x is 1, and A is -C(S)N(R 4 )-. ha another embodiment, Rj is -H.
  • R x is -CI.
  • R j is -Br. hi another embodiment, R j is -I.
  • R j is -F. ha another embodiment, R j is -(Cj-C 6 )alkyl. ha another embodiment, R, is -CH 3 . ha another embodiment, Rj is -NO 2 . ha another embodiment, R j is -CN. ha another embodiment, Rj is -OH. ha another embodiment, Rj is -OCH 3 . ha another embodiment, R j is -NH 2 . ha another embodiment, R j is -C(halo) 3 . ha another embodiment, Rj is -CH(halo) 2 . ha another embodiment, R j is -CH 2 (halo).
  • p is 1 and R 2 is -halo, -CN, -OH, -O(Cj-C 6 )alkyl, -NO 2 , or -NH 2 .
  • p is 1 and R 2 is -(Cj-C ⁇ 0 )alkyl, -(C 2 -C 10 )alkenyl, -(C 2 - C 10 )alkynyl, -(C 3 -C 10 )cycloalkyl, -(C 8 -C j4 )bicycloalkyl, -(C 8 -C ⁇ 4 )tricycloalkyl, -(C 5 - Cj 0 )cycloalkenyl,-(C 8 -C j4 )bicycloalkenyl, -(C 8 -Cj 4 )tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-
  • p is 1 and R 2 is -phenyl, -naphthyl, -(C 14 )aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups; ha another embodiment, m is 1 and R 3 is -halo, -CN, -OH, -O(C j -C 6 )alkyl, -NO 2 , or -NH 2 .
  • m is 1 and R 3 is -(C j -C 10 )alkyl, -(C 2 -C 10 )a ⁇ kenyl, -(C 2 - Cj 0 )alkynyl, -(C 3 -Cj 0 )cycloalkyl, -(C 8 -C 14 )bicycloalkyl, -(Cg-Ci 4 )tricycloalkyl, -(C 5 - Cj 0 )cycloalkenyl,-(C 8 -Cj 4 )bicycloalkenyl, -(C 8 -C j4 )tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R 5 groups.
  • m is 1 and R 3 is -phenyl, -naphthyl, -(Cj 4 )aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups.
  • R 8 and Rg are each independently -H, halo, -(C r C 6 )alkyl, -O(C j -C 6 )alkyl, -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo). ha another embodiment, at least one of R 8 or Rg is -H.
  • R j is -halo
  • x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, and R 8 and Rg are -H.
  • p and m are 0, Rj is -CI
  • x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, and R 8 and Rg are -H.
  • p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI.
  • Rg is -Br. a another embodiment, Rg is -F. ha another embodiment, p and m are 0, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. h another embodiment, R 8 is -Br. In another embodiment, R 8 is -F.
  • R j is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -halo
  • Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. ha another embodiment, R 8 is -F.
  • p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H
  • R 8 is -H
  • R, is -CH 3 .
  • Rj is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -CH 3
  • p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H
  • R 8 is -CH 3
  • Rg is -H.
  • p and m are 0, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CH 3 , and Rg is -H.
  • ha another embodiment, p and m are 0, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 . ha another embodiment, p and m are 0, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 .
  • ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and Rg is -H. ha another embodiment, p and m are 0, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and R, is -H.
  • R j is -halo
  • x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and g is -OCH 2 CH 3 .
  • p and m are 0, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • p and m are 0, R j is -halo, x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, p and m are 0, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, and R 8 and Rg are -H.
  • R t is -CH 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -halo
  • R 8 is -CI. ha another embodiment, R 8 is -Br.
  • R 8 is -F. ha another embodiment, p and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CH 3 . ha another embodiment, p and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CH 3 , and R g is -H.
  • Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 .
  • p and m are 0, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and Rg is -H.
  • p and m are 0, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -halo.
  • Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F.
  • Rj is -CF 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -halo
  • Rg is -H.
  • R 8 is -CI.
  • ha another embodiment, R 8 is -Br.
  • R 8 is -F.
  • R j is -CF 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -H
  • Rg is -CH 3
  • p and m are 0, R j is -CF 3
  • x is 1, A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -H.
  • ha another embodiment, p and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 . ha another embodiment, p and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and Rg is -H. ha another embodiment, p and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-,
  • R 4 is -H
  • R 8 is -H
  • Rg is -OCH 2 CH 3 . ha another embodiment, p and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -OCH 2 CH 3 , and R g is -H.
  • R j is -halo
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -tert-butyl
  • R g is -H
  • p and m are 0, Rj is -CI
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -tert-butyl
  • Rg is -H.
  • ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • ha another embodiment, p and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -tert-butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • Rj is -CH 3
  • x is 1
  • A is -C(O)-N(R 4 )-
  • R 4 is -H
  • R 8 is -CH 3
  • Rg is -CH 3 .
  • p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Rg is -halo, ha another embodiment, Rg is -CI.
  • Rg is -Br.
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. a another embodiment, R 8 is -Br. hi another embodiment, R 8 is -F. hi another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R, is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI. ha another embodiment, R 8 is -Br. hi another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -halo, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and R, is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and R ⁇ is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and R g is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R t is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and Rg are -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. h another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R 4 )- group, R 4 is -H, R 8 is -H, and R, is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p and m are 0, R j is -halo, x is 0, R 4 is -H, and R 8 and
  • ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, and R 8 and Rg are -H. ha another embodiment, p and m are 0, R j is -halo, x is 0, R 4 is -H, R 8 is -H, and R g is -halo, ha another embodiment, R g is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. a another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -H, and R g is -halo, ha another embodiment, Rg is -CI.
  • Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, R j is -halo, x is 0, R 4 is -H, R 8 is -halo, and Rg is -H. h another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. In another embodiment, p and m are 0, Rj is -CI, x is 0, R 4 is -H, R 8 is -halo, and Rg is -H. In another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F.
  • R j is -halo, x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -H, and h another embodiment, p and m are 0, R j is -halo, x is 0, R 4 is -H, R 8 is -CH 3 , ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -CH 3 , ha another embodiment, p and m are 0, R j is -halo, x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is
  • R j is -CH 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, Rj is -CH 3 , x is 0, R 4 is -H, R 8 is -CH 3 , ha another embodiment, p and m are 0, Rj is -CH 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, Rj is -CH 3 , x is 0, R 4 is -H, R 8 is -CF 3 , ha another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -CF 3 , ha another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is
  • ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, R g is -Br. ha another embodiment, R, is -F. ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -halo, and R g is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F.
  • R j is -CF 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -CH 3 , a another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -CF 3 , ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, p and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R
  • ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -tert- butyl, and Rg is -H. ha another embodiment, p and m are 0, R j is -halo, x is 0, R 4 is -H, R 8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, R j is -CI, x is 0, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • ha another embodiment, p and m are 0, R, is -CH 3 , x is 0, R 4 is -H, R 8 is -tert- butyl, and Rg is -H. ha another embodiment, p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • ha another embodiment p and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -CH 3 , ha another embodiment, p is 0, m is 1, R j is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R 8 and R g are -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and R, is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. hi another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI. In another embodiment, R 8 is -Br. In another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI. ha another embodiment, R 8 is -Br. a another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R g is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R g is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R 8 and Rg are -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R j is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -halo.
  • Rg is -CI. ha another embodiment,
  • Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -halo, and Rg is -H. In another embodiment, R 8 is -CI. a another embodiment,
  • R 8 is -Br. hi another embodiment, R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R g is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, R, is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R j is -CF 3 , x is 0, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -halo, and R g is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. In another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, R, is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment p is 0, m is 1, Rj is -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • p is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -CH 3 , and R g is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridazinyl group, p is 0, m is 1, R, is -CH 3 or -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridazinyl group, p is 0, m is 1, R, is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridazinyl group, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar is a pyridazinyl group
  • p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a thiazanyl group, p is 0, m is 1, Rj is -CH 3 or -halo, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a thiazanyl group
  • p is 0, m is 1, Rj is -halo, x is 1,
  • A is -C(O)-N(R 4 )-
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a thiazanyl group, p is 0, m is 1, R, is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar is a pyridazinyl group
  • p is 0, m is 1, Rj is -CH 3 or -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -halo
  • a another embodiment, the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyridazinyl group
  • p is 0, m is 1
  • Rj is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridazinyl group
  • p is 0, m is 1, R, is -halo, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridazinyl group
  • p is 0, m is 1, Rj is -CI, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a pyridazinyl group
  • p is 0, m is 1
  • R j is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH 3 or -halo, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a thiazanyl group
  • p is 0, m is 1
  • R j is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a thiazanyl group
  • p is 0, m is 1, Rj is -halo, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar is a thiazanyl group
  • p is 0, m is 1, Rj is -CI, x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Ar j is a thiazanyl group
  • p is 0, m is 1
  • Rj is -CH 3
  • x is 0,
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group
  • R 4 is -H
  • R 8 is -H
  • Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0.
  • m is 1 and R 3 is -(C ⁇ -C 4 )alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -(C j -C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0. ha another embodiment, m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0. ha another embodiment, m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -(Cj-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group
  • m is 1 and R 3 is -(C j -C 4 )alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R 3 group is attached is in the R configuration.
  • m is 1 and R 3 is -(C j -C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group
  • m is 1 and R 3 is -(C j-C 4 )alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group
  • m is 1 and R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R 3 group is attached is in the S configuration.
  • the present invention encompasses compounds of Formula (-Ha)
  • Arj is a pyridyl group. ha another embodiment, Arj is a pyrimidinyl group. ha another embodiment, x is 1 and A is -C(O)-N(R 4 )-. ha another embodiment, x is 1 and A is -C(S)-N(R 4 )-. ha another embodiment x is 0. ha another embodiment x is 1. ha another embodiment n or p is 0. ha another embodiment n or p is 1. ha another embodiment m is 0.
  • m is 1.
  • Arj is a pyridyl group, x is 1, and A is -C(O)N(R 4 )-.
  • Arj is a pyridyl group, x is 1, and A is -C(S)N(R 4 )-.
  • Arj is a pyrimidinyl group, x is 1, and A is -
  • Arj is a pyrimidinyl group
  • x is 1
  • A is
  • R j is -CI.
  • R j is -Br. hi another embodiment, R j is -I. ha another embodiment, R j is -(C j -C 6 )alkyl. ha another embodiment, R j is -CH 3 .
  • Rj is -NO 2 . ha another embodiment, Rj is -CN. ha another embodiment, Rj is -OH. ha another embodiment, R j is -OCH 3 . hi another embodiment, R j is -NH 2 .
  • R j is -C(halo) 3 . ha another embodiment, R j is -CH(halo) 2 .
  • R j is -CH 2 (halo).
  • n and p are 1 and R 2 is -halo, -CN, -OH, -O(Cj- C 6 )alkyl, -NO 2 , or -NH 2 .
  • n and p are 1 and R 2 is -(C j -C 10 )alkyl, -(C 2 - C j o)alkenyl, -(C 2 -C j0 )alkynyl, -(C 3 -C 10 )cycloalkyl, -(C 8 -C j4 )bicycloalkyl, -(C 8 - Cj 4 )tricycloalkyl, -(C 5 -C ⁇ 0 )cycloalkenyl,-(C 8 -C j4 )bicycloalkenyl, -(C 8 -C ⁇ 4 )fricycloalkenyl, -(3- to 7-membered)he
  • n and p are 1 and R 2 is -phenyl, -naphthyl, -(C j4 )aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups; ha another embodiment, m is 1 and R 3 is -halo, -CN, -OH, -O(C j -C 6 )alkyl, -NO 2 , or -NH 2 .
  • m is 1 and R 3 is -(Cj-Cj 0 )alkyl, -(C 2 -C j0 )alkenyl, -(C 2 - Cjo)alkynyl, -(C 3 -Cj 0 )cycloalkyl, -(C 8 -C j4 )bicycloalkyl, -(C 8 -C ⁇ 4 )tricycloalkyl, -(C 5 - Cj 0 )cycloalkenyl,-(C 8 -C j4 )bicycloalkenyl, -(C 8 -Cj 4 )tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R 5 groups.
  • m is 1 and R 3 is -phenyl, -naphthyl, -(C ⁇ 4 )aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R 6 groups.
  • R 4 is -H.
  • R 4 is -(Cj-C 6 )alkyl.
  • R 8 and Rg are each independently -H, halo, -(Cj- C 6 )alkyl, -O(C j -C 6 )alkyl, -C(halo) 3 , -CH(halo) 2 , or -CH 2 (halo).
  • R 8 or Rg is -H.
  • ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; and R 8 and Rg are -H.
  • ha another embodiment, n, p, and m are 0; R j is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; and R 8 and Rg are -H.
  • n, p, and m are 0; R j is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. hi another embodiment, Rg is -F.
  • n, p, and m are 0; R j is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -halo, a another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 1 ; A is - C(O)-N(R 4 )-; R 4 is -H; R 8 is -halo; and Rg is -H.
  • R 8 is -CI.
  • R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, n, p, and m are 0; R j is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -halo; and Rg is -H. ha another embodiment, R 8 is -CI.
  • R 8 is -Br. hi another embodiment, R 8 is -F. ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 1; A is
  • n, p, and m are 0; R j is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -CH 3 .
  • n, p, and m are 0; R j is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CH 3 ; and R g is -H.
  • n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CH 3 ; and Rg is -H.
  • n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H, R 8 is -H; and Rg is -CF 3 .
  • n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R 4 )-;
  • ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CF 3 ; and Rg is -H.
  • ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -CF 3 ; and Rg is -H.
  • ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • ha another embodiment, n, p, and m are 0; R j is -CI; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 1; A is
  • n, p, and m are 0; R j is -CI; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H. ha another embodiment, n, p, and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 , R 4 is -H, and R 8 and Rg are -H.
  • R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, n, p, and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CH 3 . ha another embodiment, n, p, and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CH 3 , and Rg is -H.
  • n, p, and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CF 3 .
  • n, p, and m are 0, R j is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and Rg is -H.
  • n, p, and m are 0, R j is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • n, p, and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -CH 3 .
  • n, p, and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CH 3 , and Rg is -H.
  • n, p, and m are 0, R j is -CF 3 , x is 1, A is
  • n, p, and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -CF 3 , and Rg is -H.
  • n, p, and m are 0, R j is -CF 3 , x is 1, A is -C(O)-N(R 4 )-, R 4 is -H, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • n, p, and m are 0; R j is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 8 is -tert-butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; R j is -CI; x is 1; A is -C(O)-N(R 4 )-;
  • n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1, Rj is -CI; x is 1, A is -C(O)- N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -halo, ha another embodiment Rg is - CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0; m is 1; j is -CI; x is 1; A is -C(O)- N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -halo, ha another embodiment g is -CI.
  • Rg is -Br.
  • a another embodiment, R, is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -halo; and Rg is -H. ha another embodiment R 8 is - CI. ha another embodiment, R 8 is -Br.
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -halo
  • Rg is -H. ha another embodiment R 8 is -CI.
  • R 8 is -Br. hi another embodiment, R 8 is -F. hi another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R t is -CI; x is 1; A is -C(O)- N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -CH 3 . ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 8 is -CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration
  • the carbon atom to which the R 3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration, hi another embodiment, n and p are 0
  • m is 1
  • Rj is -CI
  • x is 1
  • A is -C(O)- N(R 4 )-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -H
  • Rg is -CF 3 .
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 8 is -CF 3 ; and Rg is -H.
  • ha another embodiment the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration, ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 8 is -CF 3 ; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 8 is -H; and Rg is -OCH 2 CH 3 . ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration. a another embodiment, n and p are 0; m is 1 ; R x is -CI; x is 1 ; A is -C(O)-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -H
  • Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is
  • N(R 4 )-, R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group
  • R 8 and R are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment the carbon atom to which the R 3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -H
  • Rg is -halo
  • ha another embodiment Rg is -CI.
  • Rg is -Br.
  • ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -halo, and Rg is -H. ha another embodiment R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and R, is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, and R 8 and R, are -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -halo, h another embodiment R, is -CI. h another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, R t is -CF 3 , x is 1, A is -C(O)-
  • R 4 is -H
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group
  • R 8 is -halo
  • Rg is -H. ha another embodiment
  • R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CH 3 . ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -CF 3 , and R, is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 1, A is -C(O)- N(R 4 )-, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -tert-butyl; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R g is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)- N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; and R 8 and R g are -H. ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; and R 8 ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H;
  • R 8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. h another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H; and R g is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F.
  • ha another embodiment, n, p, and m are 0; R, is -CI, -Br, or -I; x is 0; R 4 is -H; R 8 is -halo; and Rg is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. hi another embodiment, R 8 is -F. ha another embodiment, n, p, and m are 0; R j is -CI, x is 0; R 4 is -H; R 8 is -halo; and Rg is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. In another embodiment, R 8 is -F.
  • ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H; ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; R j is -CI, x is 0;
  • ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H; ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • R j is -CI; x is 0; R 4 is -H; R 8 is ha another embodiment, n, p, and m are 0; R j is -CH 3 , x is 0; R 4 is -H, and R 8 ha another embodiment, n, p, and m are 0; R j is -CH 3 , x is 0; R 4 is -H, R 8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; R j is -CH 3 , x is 0; R 4 is -H, R 8 is
  • Rg is -H. ha another embodiment, R 8 is -CI. ha another embodiment, R 8 is -Br. In another embodiment, R 8 is -F. ha another embodiment, n, p, and m are 0; R j is -CH 3 , x is 0; R 4 is -H, R 8 is -H, ha another embodiment, n, p, and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is - ha another embodiment, n, p, and m are 0, R x is -CH 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, n, p, and m are 0, R, is -CH 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, n, p, and m are 0, R, is -CH 3 , x is 0, R 4 is -H, R 8 is -
  • n, p, and m are 0, R j is -CF 3 , x is 0, R 4 is -H, and R 8 ha another embodiment, n, p, and m are 0, Rj is -CF 3 , x is 0, R 4 is -H, R 8 is -H, and R g is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0, Rj is -CF 3 , x is 0, R 4 is -H, R 8 is -halo, and Rg is -H. ha another embodiment, R 8 is -CI.
  • R 8 is -Br. ha another embodiment, R 8 is -F. ha another embodiment, n, p, and m are 0, Rj is -CF 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, n, p, and m are 0, Rj is -CF 3 , x is 0, R 4 is -H, R 8 is ha another embodiment, n, p, and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is -H, ha another embodiment, n, p, and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is ha another embodiment, n, p, and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is ha another embodiment, n, p, and m are 0, R j is -CF 3 , x is 0, R 4 is -
  • n, p, and m are 0, R j is -CF 3 , x is 0, R 4 is -H, R 8 is ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; R 8 is -tert-butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -tert- butyl; and Rg is -H.
  • ha another embodiment, n, p, and m are 0; R j is -CI, -Br, or -I; x is 0; R 4 is -H; R 8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0; R j is -CI; x is 0; R 4 is -H; R 8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • n, p, and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is -H, and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0, R j is -CH 3 , x is 0, R 4 is -H, R 8 is a another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1, Rj is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -H; and Rg is -halo.
  • Rg is -CI.
  • Rg is -Br. ha another embodiment
  • Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -halo; and Rg is -H.
  • R 8 is -CI. ha another embodiment, R 8 is -Br. a another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0; m is 1, R j is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -halo; and Rg is -H. ha another embodiment R 8 is -CI. hi another embodiment, R 8 is -Br. a another embodiment, R 8 is -F. h another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -H; and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1, Rj is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -H; and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; R j is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R 8 is -CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p 0; m is 1; R j is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R 8 is -H; and R g is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -CF 3 ; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -CF 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; x is 0; R is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -H; and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 8 is -OCH 2 CH 3 ; and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0; m is 1; R j is -CI; x is 0; R 4 is -H; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R 8 is -OCH 2 CH 3 ; and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment the carbon atom to which the R 3 group is attached has the S configuration.
  • R 8 is -H
  • Rg is -halo
  • ha another embodiment Rg is -CI.
  • Rg is -Br.
  • ha another embodiment, Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 8 is -halo, and Rg is -H.
  • R 8 is -CI. ha another embodiment, R 8 is -Br. ha another embodiment, R 8 is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, R j is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, and R 8 and Rg are -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -halo, a another embodiment Rg is -CI. h another embodiment, Rg is -Br. ha another embodiment, R, is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -halo, and Rg is -H. ha another embodiment R 8 is -CI. ha another embodiment, R 8 is -Br. In another embodiment, R 8 is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -CF 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, R j is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -CF 3 , and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -H, and Rg is -OCH 2 CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • ha another embodiment n and p are 0, m is 1, Rj is -CF 3 , x is 0, R 4 is -H, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 8 is -OCH 2 CH 3 , and Rg is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 4 is -H, R 8 is -tert-butyl, and Rg is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 4 is -H; R 8 is -tert-butyl; and R, is -H.
  • the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 4 is -H; R 8 is -H; and Rg is -tert-butyl.
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0; m is 1; Rj is -CI; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R 4 is -H; R 8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 4 is -H, R 8 is -tert-butyl, and R, is -H. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 4 is -H, R 8 is -H, and R g is -tert-butyl. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • n and p are 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 4 is -H, R 8 is -CH 3 , and Rg is -CH 3 .
  • the carbon atom to which the R 3 group is attached has the R configuration
  • ha another embodiment, the carbon atom to which the R 3 group is attached has the S configuration.
  • Arj is a pyridyl group; n is 0; m is 1; Rj is -CH 3 , -CI, -Br, or -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and Rg is -halo.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Ar is a pyridyl group, n is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyridyl group; n is 0; m is 1; Rj is -CI, -Br, or
  • x is 1;
  • A is -C(O)-N(R 4 )-;
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group;
  • R 4 is -H;
  • R 8 is -H; and
  • Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Ar is a pyridyl group
  • n is 0, m is 1, Rj is -CI, x is 1,
  • A is -C(O)-N(R 4 )-
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group
  • R 4 is -H
  • R 8 is -H
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyridyl group, n is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyrimidinyl group; p is 0; m is 1; R x is -CH 3 , -CI, -Br, -I; x is 1; A is -C(O)-N(R 4 )-; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • Ar j is a pyrimidinyl group, p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • Ar j is a pyrimidinyl group; p is 0; m is 1; Rj is -CI,
  • x is 1;
  • A is -C(O)-N(R 4 )-;
  • R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group;
  • R 4 is -H;
  • R 8 is -H; and
  • Rg is -Br. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH 3 , x is 1, A is -C(O)-N(R 4 )-, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R 4 )- group, R 4 is -H, R 8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyridyl group; n is 0; m is 1; Rj is -CH 3 , -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyridyl group, n is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 4 is -H, R 8 is -H, and Rg is -CI.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyridyl group; n is 0; m is 1; R j is -CI, -Br, or
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Ar j is a pyridyl group, n is 0, m is 1, Rj is -CI, x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R 4 is -H, R 8 is -H, and Rg is -Br.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyridyl group, n is 0, m is 1, Rj is -CH 3 , x is 0, R 3 is -CH 3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R 4 is -H, R 8 is -H, and Rg is -F.
  • the carbon atom to which the R 3 group is attached has the R configuration.
  • Arj is a pyrimidinyl group; p is 0; m is 1; Rj is -CH 3 , -CI, -Br, or -I; x is 0; R 3 is -CH 3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R 4 is -H; R 8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R 3 group is attached has the R configuration.

Abstract

A compound of formula (I) wherein Ar1, A, R3, x, and m are as disclosed herein and Ar2 is a benzothiazolyl, benzooxazolyl, or benzoimidazolyl group or a pharmaceutically acceptable salt thereof (a “Benzoazolylpiperazine Compound”), compositions comprising a Benzoazolylpiperazine Compound, and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson’s disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, retricted brain function, Huntington’s chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of Benzoazolylpiperazine Compound are disclosed.

Description

BENZOAZOLYPIPERAZINE DERIVATIVES HAVING MGLURl- AND MGLUR5-ANTAGONISTIC ACTIVITY
This application claims the benefit of U.S. Provisional Application No. 60/435,917, filed December 24, 2002; U.S. Provisional Application No. 60/459,626, filed April 3, 2003; and U.S. Provisional Application No. 60/473,856, filed May 29, 2003, all of which are incorporated herein by reference in their entirety.
1. FIELD OF THE INVENTION
The present invention relates to Benzoazolylpiperazine Compounds, 0 compositions comprising a Benzoazolylpiperazine Compound and methods for treating or preventing pain, urinary incontinence (UI), an ulcer, inflainniatory-bowel disease (BD), irritable-bowel syndrome (IBS), an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis 5 (ALS), dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression, comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound.
2. BACKGROUND OF THE INVENTION 0 Pain is the most common symptom for which patients seek medical advice and treatment. Pain can be acute or chronic. While acute pain is usually self-limited, chronic pain persists for 3 months or longer and can lead to significant changes in a patient's personality, lifestyle, functional ability and overall quality of life (K.M. Foley, Pain, in Cecil Textbook of Medicine 100-107 (J.C. Bennett and F. Plum eds., 20th ed. 1996)). 5 Pain has been traditionally managed by administering non-opioid analgesics, such as acetylsalicylic acid, choline magnesium trisalicylate, acetaminophen, ibuprofen, fenoprofen, diflusinal, and naproxen; or opioid analgesics, including morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone, and oxymorphone. Id.
UI is uncontrollable urination, generally caused by bladder-detrusor-muscle 0 instability. UI affects people of all ages and levels of physical health, both in health care settings and in the community at large. At present, UI afflicts 15-30% of elderly people living at home, one-third of those living in acute-care settings, and at least one-half of those living in long-term care institutions (R.M. Resnick, Lancet 346:94 (1995)). Persons having UI are predisposed to also having urinary-tract infections, pressure ulcers, perineal rashes and urosepsis. Psychosocially, UI is associated with embarrassment, social stigmatization, depression and a risk of institutionalization (Herzo et al, Annu. Rev. Gerontol. Geriatr. 9:1 A (1989)). Economically, the costs of UI are great; in the United States alone, health-care costs associated with UI are over $15 billion per annum.
Physiologic bladder contraction results in large part from acetylcholine- induced stimulation of post-ganglionic muscarinic-receptor sites on bladder smooth muscle. Treatments for UI include the admimstration of drugs having bladder-relaxant properties, which help to control bladder-detrusor-muscle overactivity. For example, anticholmergics such as propantheline bromide and glycopyrrolate, and combinations of smooth-muscle relaxants such as a combination of racemic oxybutynin and dicyclomine or an anticholinergic, have been used to treat UI (See, e.g., AJ. Wein, Urol Clin. N. Am. 22:557-577 (1995); Levin et al, J. Urol. 128:396-398 (1982); Cooke et al, S. Afr. Med. J. 63:3 (1983); R.K. Mirakhur et al, Anaesthesia 38: 1195-1204 (1983)). These drugs are not effective, however, in all patients having uninhibited bladder contractions. Administration of anticholinergic medications represent the mainstay of this type of treatment.
None of the existing commercial drug treatments for UI, however, has achieved complete success in all classes of UI patients, nor has treatment occurred without significant adverse side effects. For example, drowsiness, dry mouth, constipation, blurred vision, headaches, tachycardia, and cardiac arrhythmia, which are related to the anticholinergic activity of traditional anti-UI drugs, can occur frequently and adversely affect patient compliance. Yet despite the prevalence of unwanted anticholinergic effects in many patients, anticholinergic drugs are currently prescribed for patients having UI. The Merck Manual of Medical Information 631-634 (R. Berkow ed., 1997).
Ulcers are sores occurring where the lining of the digestive tract has been eroded by stomach acids or digestive juices. The sores are typically well-defined round or oval lesions primarily occurring in the stomach and duodenum. About 1 in 10 people develop an ulcer. Ulcers develop as a result of an imbalance between acid-secretory factors, also known as "aggressive factors," such as stomach acid, pepsin, and Helicobacter pylori infection, and local ucosal-protective factors, such as secretion of bicarbonate, mucus, and prostaglandins.
Treatment of ulcers typically involves reducing or inhibiting the aggressive factors. For example, antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate can be used to neutralize stomach acids. Antacids, however, can cause alkalosis, leading to nausea, headache, and weakness. Antacids can also interfere with the absorption of other drugs into the blood stream and cause diarrhea.
H2 antagonists, such as cimetidine, ranitidine, famotidine, and nizatidine, are also used to treat ulcers. H2 antagonists promote ulcer healing by reducing gastric acid and digestive-enzyme secretion elicited by histamine and other H2 agonists in the stomach and duodenum. H2 antagonists, however, can cause breast enlargement and impotence in men, mental changes (especially in the elderly), headache, dizziness, nausea, myalgia, diarrhea, rash, and fever.
H+, K+ - ATPase inhibitors such as omeprazole and lansoprazole are also used to treat ulcers, it, K+ - ATPase inhibitors inhibit the production of enzymes used by the stomach to secrete acid. Side effects associated with H+, K+ - ATPase inhibitors include nausea, diarrhea, abdominal colic, headache, dizziness, somnolence, skin rashes, and transient elevations of plasma activities of aminotransferases.
Sucraflate is also used to treat ulcers. Sucraflate adheres to epithelial cells and is believed to form a protective coating at the base of an ulcer to promote healing. Sucraflate, however, can cause constipation, dry mouth, and interfere with the absorption of other drugs.
Antibiotics are used when Helicobader pylori is the underlying cause of the ulcer. Often antibiotic therapy is coupled with the administration of bismuth compounds such as bismuth subsalicylate and colloidal bismuth citrate. The bismuth compounds are believed to enhance secretion of mucous and HCO3 ", inhibit pepsin activity, and act as an antibacterial against H. pylori, higestion of bismuth compounds, however, can lead to elevated plasma concentrations of Bi+3 and can interfere with the absorption of other drugs.
Prostaglandin analogues, such as misoprostal, inhibit secretion of acid and stimulate the secretion of mucous and bicarbonate and are also used to treat ulcers, especially ulcers in patients who require nonsteroidal anti-inflammatory drugs. Effective oral doses of prostaglandin analogues, however, can cause diarrhea and abdominal cramping. In addition, some prostaglandin analogues are abortifacients.
Carbenoxolone, a mineral corticoid, can also be used to treat ulcers.
Carbenoxolone appears to alter the composition and quantity of mucous, thereby enhancing the mucosal barrier. Carbenoxolone, however, can lead to Na+ and fluid retention, hypertension, hypokalemia, and impaired glucose tolerance.
Muscarinic cholinergic antagonists such as pirenzapine and telenzapine can also be used to reduce acid secretion and treat ulcers. Side effects of muscarinic cholinergic antagonists include dry mouth, blurred vision, and constipation. The Merck Manual of Medical Information 496-500 (R. Berkow ed., 1997) and Goodman and Gilman 's The
Pharmacological Basis of Therapeutics 901-915 (J. Hardman and L. Limbird eds., 9th ed.
1996).
IBD is a chronic disorder in which the bowel becomes inflamed, often causing recurring abdominal cramps and diarrhea. The two types of IBD are Crohn's disease and ulcerative colitis.
Crohn's disease, which can include regional enteritis, granulomatous ileitis, and ileocolitis, is a chronic inflammation of the intestinal wall. Crohn's disease occurs equally in both sexes and is more common in Jews of eastern-European ancestry. Most cases of Crohn's disease begin before age 30 and the majority start between the ages of 14 and 24. The disease typically affects the full thickness of the intestinal wall. Generally the disease affects the lowest portion of the small intestine (ileum) and the large intestine, but can occur in any part of the digestive tract.
Early symptoms of Crohn's disease are chronic diarrhea, crampy abdominal pain, fever, loss of appetite, and weight loss. Complications associated with Crohn's disease include the development of intestinal obstructions, abnormal connecting channels (fistulas), and abscesses. The risk of cancer of the large intestine is increased in people who have
Crohn's disease. Often Crohn's disease is associated with other disorders such as gallstones, inadequate absorption of nutrients, amyloidosis, arthritis, episcleritis, aphthous stomatitis, erythema nodosum, pyoderma gangrenosum, ankylosing spondylitis, sacroilitis, uveitis, and primary sclerosing cholangitis. There is no known cure for Crohn's disease. Cramps and diarrhea, side effects associated with Crohn's disease, can be relieved by anticholinergic drugs, diphenoxylate, loperamide, deodorized opium tincture, or codeine. Generally, the drug is taken orally before a meal.
Broad-spectrum antibiotics are often administered to treat the symptoms of Crohn's disease. The antibiotic metronidazole is often administered when the disease affects the large intestine or causes abscesses and fistulas around the anus. Long-term use of metronidazole, however, can damage nerves, resulting in pins-and-needles sensations in the arms and legs. Sulfasalazine and chemically related drugs can suppress mild inflammation, especially in the large intestine. These drugs, however, are less effective in sudden, severe flare-ups. Corticosteroids, such as prednisone, reduce fever and diarrhea and relieve abdominal pain and tenderness. Long-term corticosteroid therapy, however, invariably results in serious side effects such as high blood-sugar levels, increased risk of infection, osteoporosis, water retention, and fragility of the skin. Drugs such as azathioprine and mercaptourine can compromise the immune system and are often effective for Crohn's disease in patients that do not respond to other drugs. These drugs, however, usually need 3 to 6 months before they produce benefits and can cause serious side effects such as allergy, pancreatitis, and low white-blood-cell count.
When Crohn's disease causes the intestine to be obstructed or when abscesses or fistulas do not heal, surgery can be necessary to remove diseased sections of the intestine. Surgery, however, does not cure the disease, and inflammation tends to recur where the intestine is rejoined. In almost half of the cases a second operation is needed. The Merck Manual of Medical Information 528-530 (R. Berkow ed., 1997).
Ulcerative colitis is a chronic disease in which the large intestine becomes inflamed and ulcerated, leading to episodes of bloody diarrhea, abdominal cramps, and fever. Ulcerative colitis usually begins between ages 15 and 30; however, a small group of people have their first attack between ages 50 and 70. Unlike Crohn's disease, ulcerative colitis never affects the small intestine and does not affect the full thickness of the intestine. The disease usually begins in the rectum and the sigmoid colon and eventually spreads partially or completely through out the large intestine. The cause of ulcerative colitis is unknown. Treatment of ulcerative colitis is directed to controlling iriflammation, reducing symptoms, and replacing lost fluids and nutrients. Anticholinergic drugs and low doses of diphenoxylate or loperamide are administered for treating mild diarrhea. For more intense diarrhea higher doses of diphenoxylate or loperamide, or deodorized opium tincture or codeine are administered. Sulfasalazine, olsalazie, prednisone, or mesalamine can be used to reduce inflammation. Azathioprine and mercaptopurine have been used to maintain remissions in ulcerative-colitis patients who would otherwise need long-term corticosteroid treatment. In severe cases of ulcerative colitis the patient is hospitalized and given corticosteroids intravenously. People with severe rectal bleeding can require transfusions and intravenous fluids. If toxic colitis develops and treatments fail, surgery to remove the large intestine can be necessary. Non-emergency surgery can be performed if cancer is diagnosed, precancerous legions are detected, or unremitting chronic disease would otherwise make the person an invalid or dependent on high doses of corticosteroids. Complete removal of the large intestine and rectum permanently cures ulcerative colitis. The Merck Manual of Medical Information 530-532 (R. Berkow ed., 1997) and Goodman and Gilman 's The Pharmacological Basis of Therapeutics (J. Hardman and L. Limbird eds., 9th ed. 1996). IBS is a disorder of motility of the entire gastrointestinal tract, causing abdominal pain, constipation, and/or diarrhea. IBS affects three-times more women than men. In IBS stimuli such as stress, diet, drugs, hormones, or irritants can cause the gastrointestinal tract to contract abnormally. During an episode of IBS contractions of the gastrointestinal tract become stronger and more frequent, resulting in the rapid transit of food and feces through the small intestine, often leading to diarrhea. Cramps result from the strong contractions of the large intestine and increased sensitivity of pain receptors in the large intestine.
There are two major types of IBS. The first type, spastic-colon type, is commonly triggered by eating, and usually produces periodic constipation and diarrhea with pain. Mucous often appears in the stool. The pain can come in bouts of continuous dull aching pain or cramps, usually in the lower abdomen. The person suffering from spastic- colon type IBS can also experience bloating, gas, nausea, headache, fatigue, depression, anxiety, and difficulty concentrating. The second type of IBS usually produces painless diarrhea or constipation. The diarrhea can begin suddenly and with extreme urgency. Often the diarrhea occurs soon after a meal and can sometimes occur immediately upon awakening. Treatment of IBS typically involves modification of an IBS-patient's diet. Often it is recommended that an IBS patient avoid beans, cabbage, sorbitol, and fructose. A low-fat, high-fiber diet can also help some IBS patients. Regular physical activity can also help keep the gastrointestinal tract functioning properly. Drugs such as propantheline that slow the function of the gastrointestinal tract are generally not effective for treating IBS. Antidiarrheal drugs, such as diphenoxylate and loperamide, help with diarrhea. The Merck Manual of Medical Information 525-526 (R. Berkow ed., 1997).
Many drugs can cause physical and or psychological addiction. Those most well known types of these drugs include opiates, such as heroin, opium, and morphine; sympathomimetics, including cocaine and amphetamines; sedative-hypnotics, including alcohol, benzodiazepines and barbiturates; and nicotine, which has effects similar to opioids and sympathomimetics. Drug addiction is characterized by a craving or compulsion for taking the drug and an inability to limit its intake. Additionally, drug dependence is associated with drug tolerance, the loss of effect of the drug following repeated administration, and withdrawal, the appearance of physical and behavioral symptoms when the drug is not consumed. Sensitization occurs if repeated administration of a drug leads to an increased response to each dose. Tolerance, sensitization, and withdrawal are phenomena evidencing a change in the central nervous system resulting from continued use of the drug. This change can motivate the addicted individual to continue consuming the drug despite serious social, legal, physical and/or professional consequences. (See, e.g., U.S. Patent No. 6,109,269 to Rise et al).
Certain pharmaceutical agents have been administered for treating addiction. U.S. Patent No. 5,556,838 to Mayer et al. discloses the use of nontoxic NMDA-blocking agents co-administered with an addictive substance to prevent the development of tolerance or withdrawal symptoms. U.S. Patent No. 5,574,052 to Rose et al. discloses co- administration of an addictive substance with an antagonist to partially block the pharmacological effects of the substance. U.S. Patent No. 5,075,341 to Mendelson et al. discloses the use of a mixed opiate agonist/antagonist to treat cocaine and opiate addiction. U.S. Patent No. 5,232,934 to Downs discloses administration of 3-phenoxypyridine to treat addiction. U.S. Patents No. 5,039,680 and 5,198,459 to Imperato et al. disclose using a serotonin antagonist to treat chemical addiction. U.S. Patent No. 5,556,837 to Nestler et. al. discloses infusing BDNF or NT-4 growth factors to inhibit or reverse neurological adaptive changes that correlate with behavioral changes in an addicted individual. U.S. Patent. No. 5,762,925 to Sagan discloses implanting encapsulated adrenal medullary cells into an animal's central nervous system to inhibit the development of opioid intolerance. U.S. Patent No. 6,204,284 to Beer et al. discloses racemic (±)-l-(3,4-dichlorophenyl)-3- azabicyclo[3.1.0]hexane for use in the prevention or relief of a withdrawal syndrome resulting from addiction to drugs and for the treatment of chemical dependencies.
Parkinson's disease is a clinical syndrome comprising bradykinesia (slowness and poverty of movement), muscular rigidity, resting tremor (which usually abates during voluntary movement), and an impairment of postural balance leading to disturbance of gait and falling. The features of Parkinson's disease are a loss of pigmented, dopaminergic neurons of the substantia nigra pars compacta and the appearance of intracellular inclusions known as Lewy bodies (Goodman and Gillman 's The Pharmaceutical Basis of Therapeutics 506 (9th ed. 1996)). Without treatment, Parkinson's disease progresses to a rigid akinetic state in which patients are incapable of caring for themselves. Death frequently results from complications of immobility, including aspiration pneumonia or pulmonary embolism. Drugs commonly used for the treatment of Parkinson's disease include carbidopa/levodopa, pergolide, bromocriptine, selegiline, amantadine, and trihexyphenidyl hydrochloride. There remains, however, a need for drugs useful for the treatment of Parkinson's disease and having an improved therapeutic profile.
Anxiety is a fear, apprehension, or dread of impending danger often accompanied by restlessness, tension, tachycardia, and dyspnea. Other symptoms commonly associated with anxiety include depression, especially accompanied with dysthymic disorder (chronic "neurotic" depression); panic disorder; agoraphobia and other specific phobias; eating disorders; and many personality disorders. Often anxiety is unattached to a clearly identified treatable primary illness. If a primary illness is found, however, it can be desirable to deal with the anxiety at the same time as the primary illness.
Currently, benzodiazepines are the most commonly used anti-anxiety agents for generalized anxiety disorder. Benzodiazepines, however, carry the risk of producing impairment of cognition and skilled motor functions, particularly in the elderly, which can result in confusion, delerium, and falls with fractures. Sedatives are also commonly prescribed for treating anxiety. The azapirones, such as buspirone, are also used to treat moderate anxiety. The azapirones, however, are less useful for treating severe anxiety accompanied with panic attacks.
Epilepsy is a disorder characterized by the tendency to have recurring seizures. The etiology commonly consists of lesions in some part of the cortex, such as a tumor; developmental malformation; or damage due to trauma or stroke. In some cases the etiology is genetic. An epileptic seizure can be triggered by repetitive sounds, flashing lights, video games, or touching certain parts of the body. Epilepsy is typically treated with anti-seizure drugs. In epilepsy cases, where anti-seizure drugs are ineffective, and the defect in the brain is isolated to a small area of the brain, surgical removal of that part of the brain can be helpful in alleviating the seizures. In patients who have several sources for the seizures or who have seizures that spread quickly to all parts of the brain, surgical removal of the nerve fibers that connect the two sides of the brain can be helpful.
Examples of drugs for treating a seizure and epilepsy include carbamazepine, ethosuximide, gabapentin, lamotrignine, phenobarbital, phenytoin, primidone, valproic acid, trimethadione, bemzodiaepines, γ-vinyl GABA, acetazolamide, and felbamate. Anti-seizure drugs, however, can have side effects such as drowsiness; hyperactivity; hallucinations; inability to concentrate; central and peripheral nervous system toxicity, such as nystagmus, ataxia, diplopia, and vertigo; gingival hyperplasia; gastrointestinal disturbances such as nausea, vomiting, epigastric pain, and anorexia; endocrine effects such as inhibition of antidiuretic hormone, hyperglycemia, glycosuria, osteomalacia; and hypersensitivity such as scarlatiniform rash, morbilliform rash, Stevens-Johnson syndrome, systemic lupus erythematosus, and hepatic necrosis; and hematological reactions such as red-cell aplasia, agranulocytosis, thrarnbocytopenia, aplastic anemia, and megaloblastic anemia. The Merck Manual of Medical Information 345-350 (R. Berkow ed., 1997).
A seizure is the result of abnormal electrical discharge in the brain. The discharge can involve a small area of the brain and lead to the person only noticing an odd taste or smell or it can involve a large area of the brain and lead to convulsions, i.e., a seizure that causes jerking and spasms of the muscles throughout the body. Convulsions can also result in brief attacks of altered consciousness and loss of consciousness, muscle control, or bladder control. A seizures is often preceded by auras, i.e., unusual sensations of smell, taste, or vision or an intense feeling that a seizure is about to begin. A seizure typically lasts for about 2 to 5 minutes. When the seizure ends the person can have headache, sore muscles, unusual sensations, confusion, and profound fatigue (postictal state). Usually the person cannot remember what happened during the seizure. A stroke or cerebro vascular accident, is the death of brain tissue (cerebral infarction) resulting from the lack of blood flow and insufficient oxygen to the brain. A stroke can be either ischemic or hemorrhagic. In an ischemic stroke, blood supply to the brain is cut off because of athersclerosis or a blood clot that has blocked a blood vessel, a hemorrhagic stroke, a blood vessel bursts preventing normal blood flow and allowing blood to leak into an area of the brain and destroying it. Most strokes develop rapidly and cause brain damage within minutes. In some cases, however, strokes can continue to worsen for several hours or days. Symptoms of strokes vary depending on what part of the brain is effected. Symptoms include loss or abnormal sensations in an arm or leg or one side of the body, weakness or paralysis of an arm or leg or one side of the body, partial loss of vison or hearing, double vision, dizziness, slurred speech, difficulty in thinking of the appropriate word or saying it, inability to recognize parts of the body, unusual movements, loss of bladder control, imbalance, and falling, and fainting. The symptoms can be permanent and can be associated with coma or stupor. Strokes can cause edema or swelling of the brain which can further damage brain tissue. For persons suffering from a stroke, intensive rehabilitation can help overcome the disability caused by impairment of brain tissue. Rehabilitation trains other parts of the brain to assume the tasks previously performed by the damaged part.
Examples of drugs for treating strokes include anticoagulants such as heparin, drugs that break up clots such as streptokinase or tissue plasminogen activator, and drugs that reduce swelling such as mannitol or corticosteroids. The Merck Manual of Medical Information 352-355 (R. Berkow ed., 1997).
Pruritus is an unpleasant sensation that prompts scratching. Pruritus can be attributed to dry skin, scabies, dermatitis, herpetiformis, atopic dermatitis, pruritus vulvae et ani, miliaria, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria, urticarial eruptions of pregnancy, psoriasis, lichen planus, lichen simplex chronicus, exfoliative dermatitis, folliculitis, bullous pemphigoid, and fiberglass dermatitis. Conventionally, pruritus is treated by phototherapy with ultraviolet B or PUNA or with therapeutic agents such as naltrexone, nalmefene, danazol, tricyclics, and antidepressants.
Selective antagonists of the metabotropic glutamate receptor 5 ("mGluR5") have been shown to exert analgesic activity in in vivo animal models (K. Walker et al, Neuropharmacology 40: 1 -9 (2000) and A. Dogrul et al. , Neuroscience Letters, 292(2) : 115- 118 (2000)).
Selective antagonists of the mGluR5 receptor have also been shown to exert anxiolytic and anti-depressant activity in in vivo animal models (E. Tatarczynska et al, Br. J. Pharmacol. 132(7): 1423-1430 (2001) and P. J.M. Will et al, Trends in Pharmacological Sciences 22(1):331-37 (2001)).
Selective antagonists of the mGluR5 receptor have also been shown to exert anti-Parkinson activity in vivo (K. J. Ossowska et al, Neuropharmacology 41(4):413-20 (2001) and P.J.M. Will et al, Trends in Pharmacological Sciences 22(7):331-37 (2001)).
Selective antagonists of the mGluR5 receptor have also been shown to exert anti-dependence activity in vivo (C. Chiamulera et al, Nature Neuroscience 4(9):873-74 (2001)).
U.S. Patent No. 6,150,129 to Cook et al. describes a class of dinitrogen heterocycles useful as antibiotics.
U.S. Patent No. 5,529,998 to Habich et al. describes a class of benzooxazolyl- and benzothiazolyloxazolidones useful as antibacterials.
International publication no. WO 01/57008 describes a class of 2- benzothiazolyl urea derivatives useful as inhibitors of serine/threonine and tyrosine kinases.
International publication no. WO 02/08221 describes aryl piperazine compounds useful for treating chronic and acute pain conditions, itch, and urinary incontinence.
International publication no. WO 99/37304 describes substituted oxoazaheterocycly compounds useful for inhibiting factor Xa.
International publication no. WO 00/59510 describes aminopyrimidines useful as sorbitol dehydrogenase inhibitors. Japanese patent application no. 11-199573 to iyoshi et al. describes benzothiazole derivatives that are neuronal 5HT3 receptor agonists in the intestinal canal nervous system and useful for treating digestive disorders and pancreatic insufficiency.
German patent application no 199 34 799 to Rainer et al. describes a chiral- smectic liquid crystal mixture containing compounds with 2 linked (hetero)aromatic rings or compounds with 3 linked (hetero)aromatic rings.
M. Chu-Moyer et al, J. Med. Chem. 45:511-528 (2002) describes heterocycle- substituted piperazino-pyrimidines useful as sorbitol dehydrogenase inhibitors.
B.G. Khadse et al, Bull. Haff. Instt. l(3):27-32 (1975) describes 2-(N4- substiruted-N'-piperazinyl) pyrido(3,2-d)thiazoles and 5-nitro-2-(N4-substituted-N1- piperazinyl)benzthiazoles useful as anthelmintic agents.
There remains, however, a clear need in the art for new drugs useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression.
Citation of any reference in Section 2 of this application is not to be construed as an admission that such reference is prior art to the present application.
3. SUMMARY OF THE INVENTION
The present invention encompasses compounds having the formula (la):
Figure imgf000013_0001
(la) and pharmaceutically acceptable salts thereof, wherein
ATJ is
Figure imgf000014_0001
A is
Figure imgf000014_0002
R, is -CI, -Br, -I, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C1o)alkynyl, -(C3- Cιo)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8-
C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-CI0)alkynyl, -(C3-
Cιo)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(1- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and R are each independently -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; m is 0 or l; and x is O or 1. The present invention encompasses compounds having the formula (lb):
Figure imgf000016_0001
(lb) and pharmaceutically acceptable salts thereof, wherein
ATJ is
Figure imgf000016_0002
A is
Figure imgf000016_0003
R, is -H, -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-CI0)alkynyl, -(C3- Ci0)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-Ci4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rs groups; or (c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(Cj-C^alkyl; each Rj is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7,
-NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is 0 or 1; and x is O or 1.
The present invention encompasses compounds having the formula (Ha):
Figure imgf000018_0001
(Ha) and pharmaceutically acceptable salts thereof, wherein ATJ is
Figure imgf000018_0002
R, is -CI, -Br, -I, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3-
C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or (c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Re, are each independently -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3,-N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; R10 is -H or -(CrC4)alkyl; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; and m is 0 or 1. The present invention encompasses compounds having the formula (lib):
Figure imgf000020_0001
(nb) and pharmaceutically acceptable salts thereof, wherein Aη is
Figure imgf000020_0002
A is
Figure imgf000020_0003
Rj is -H, -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and R<, are each independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7;
R10 is -H or -(CrC4)alkyl; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is 0 or 1; and x is O or 1.
The present invention encompasses compounds having the formula (Ilia):
Figure imgf000022_0001
(ma) and pharmaceutically acceptable salts thereof, wherein A is
Figure imgf000022_0002
A is
Figure imgf000022_0003
R, is -CI, -Br, -I, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-Cι4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7,
-NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -00(0)01^, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; m is O or 1; and x is O or 1.
The present invention encompasses compounds having the formula (IJJb):
Figure imgf000024_0001
(Hlb) and pharmaceutically acceptable salts thereof, wherein AT, is
Figure imgf000024_0002
A is
Figure imgf000024_0003
R, is -H, -halo, -(C1-C6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3-
C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, or-(C14)aryl each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- Cι4)bicycloalkenyl, -(C8-Ci4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and R, are each independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo) )22, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is 0 or 1; and x is 0 or 1.
The present invention also encompasses compounds having the formula (INa):
Figure imgf000026_0001
(INa) and pharmaceutically acceptable salts thereof, wherein Arj is
Figure imgf000026_0002
Ar2 is
Figure imgf000026_0003
Rj is -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-Ci4)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rj groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R3 is -H or -CH3: each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7,
-NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rj are each independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; and p is an integer ranging from 0 to 2. The present invention also encompasses compounds having the formula (INb):
Figure imgf000028_0001
(INb) and pharmaceutically acceptable salts thereof, wherein
Figure imgf000028_0002
Ar, is
Figure imgf000028_0003
A is
Figure imgf000028_0004
Ri is -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(C1-C6)alkyl, -NO2, or -NH2;
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R3 is -CH3;
R4 is -H or -(CrC6)alkyl; each Rj is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C^C^a-kyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2,
-CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; and x is O or 1. The present invention also encompasses compounds having the formula (N):
Figure imgf000030_0001
(N) and pharmaceutically acceptable salts thereof, wherein Arl is
Figure imgf000030_0002
Ar9 is
Figure imgf000030_0003
R! is -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R3 is -H or -CH3: each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H,
Figure imgf000031_0001
-(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Re, are each independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; and p is an integer ranging from 0 to 2.
A compound of formula (la), (lb), (Ha), (lib), (IHa), (mb), (INa), (INb), and (N) or a pharmaceutically acceptable salt thereof (a "Benzoazolylpiperazine Compound") is useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, apruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal. The invention also relates to compositions comprising an effective amount of a Benzoazolylpiperazine Compound and a pharmaceutically acceptable carrier or excipient. The compositions are useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal.
The invention further relates to methods for treating pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound.
The invention further relates to methods for preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression comprising administering to an animal in need thereof an effective amount of a Benzoazolylpiperazine Compound. The invention still further relates to methods for inhibiting Nanilloid Receptor
1 ("NR1") function in a cell, comprising contacting a cell capable of expressing NR1 with an effective amount of a Benzoazolylpiperazine Compound.
The invention still further relates to methods for inhibiting mGluR5 function in a cell, comprising contacting a cell capable of expressing mGluR5 with an effective amount of a Benzoazolylpiperazine Compound.
The invention still further relates to methods for inhibiting metabotropic glutamate receptor 1 ("mGluRl") function in a cell, comprising contacting a cell capable of expressing mGluRl with an effective amount of a Benzoazolylpiperazine Compound.
The invention still further relates to a method for preparing a composition comprising the step of admixing a Benzoazolylpiperazine Compound and a pharmaceutically acceptable carrier or excipient. The invention still further relates to a kit comprising a container containing an effective amount of a Benzoazolylpiperazine Compound.
The present invention still further relates to a compound selected from the group consisting of
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000034_0002
and pharmaceutically acceptable salts thereof.
The present invention still further relates to a compound selected from the group consisting of
Figure imgf000035_0001
Figure imgf000035_0002
Figure imgf000036_0001
Figure imgf000036_0002
and pharmaceutically acceptable salts thereof.
The present invention still further relates to a compound selected from the group consisting of
Figure imgf000037_0001
and pharmaceutically acceptable salts thereof. The present invention can be understood more fully by reference to the following detailed description and illustrative examples, which are intended to exemplify non-limiting embodiments of the invention.
4. DETAILED DESCRIPTION OF THE INVENTION 4.1 The Compounds of Formula (la)
As stated above, the present invention encompasses compounds of Formula
(la)
Figure imgf000038_0001
(la) and pharmaceutically acceptable salts thereof, where Arl5 R3, R8, Rg, A, x, and m, are defined above for the Benzoazolylpiperazine Compounds of formula (la). In one embodiment, A j is a pyridyl group, hi another embodiment, ATJ is a pyrimidinyl group. In another embodiment, x is 1 and A is -C(O)-N(R4)-. In another embodiment, x is 1 and A is -C(S)-N(R4)-.
In another embodiment x is 0. In another embodiment, n or p is 0. In another embodiment, n or p is 1. In another embodiment, m is 0. In another embodiment, m is 1.
In another embodiment, R4 is -H. In another embodiment, R4 is -(CrC6)alkyl.
In another embodiment, ATJ is a pyridyl group, x is 1, and A is -C(O)N(R4)-. In another embodiment, A is a pyridyl group, x is 1, and A is -C(S)N(R4)-. hi another embodiment, Ar{ is a pyrimidinyl group, x is 1, and A is -
C(O)N(R4)-. hi another embodiment, Axx is a pyrimidinyl group, x is 1, and A is -
C(S)N(R4)-.
In another embodiment, Rλ is -CI. In another embodiment, Rj is -Br. hi another embodiment, Rj is -I.
In another embodiment, R, is -(C,-C6)alkyl. h another embodiment, Rj is -CH3. hi another embodiment, R, is -NO2. In another embodiment, Rλ is -CN. hi another embodiment, R{ is -OH.
In another embodiment, Rx is -OCH3. hi another embodiment, Rx is -NH2. In another embodiment, Rj is -C(halo)3. In another embodiment, R1 is -CH(halo)2. In another embodiment, Rx is -CH2(halo).
In another embodiment, n and p are 1 and R2 is -halo, -CN, -OH, -O(C C6)alkyl, -NO2, or -NH2.
In another embodiment, n and p are 1 and R2 is -(CrC10)alkyl, -(C2- C10)alkenyl, -(C2-C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-Cι4)bicycloalkyl, -(C8- C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8-C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
In another embodiment, n and p are 1 and R2 is -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; h another embodiment, m is 1 and R3 is -halo, -CN, -OH, -O^-C^aU l, -NO2, or -NH2.
In another embodiment, m is 1 and R3 is -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2- C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5- C10)cycloalkenyl,-(C8-C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
In another embodiment, m is 1 and R3 is -phenyl, -naphthyl, -(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups.
In another embodiment, R8 and Re, are each independently -H, -halo, -(Cr C6)alkyl, -O(CrC6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo).
In another embodiment, at least one of R8 and Rn is -H.
In another embodiment, n, p, and m are 0; R{ is -CI -Br, or, -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; and R8 and Rg are -H. hi another embodiment, n, p, and m are 0; Rj is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H.
In another embodiment, n, p, and m are 0; Rx is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -halo, hi another embodiment, Rj is -CI. hi another embodiment, Rg is -CI. another embodiment, Rg is -Br. In another embodiment,
hi another embodiment, n, p, and m are 0; R{ is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, R! is -CI. hi another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. hi another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1 ; A is
-C(O)-N(R4)-; R4 is -H; R8 is -halo; and Rg is -H. hi another embodiment, R, is -CI. h another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0; Rt is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, Rj is -CI. hi another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, n, p, and m are 0; Rx is -CI -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CH3.
In another embodiment, n, p, and m are 0; R, is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. hi another embodiment, n, p, and m are 0; Rj is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CH3; and Rg is -H.
In another embodiment, n, p, and m are 0; Ri is -C^ x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. h another embodiment, n, p, and m are 0; R, is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CF3.
In another embodiment, n, p, and m are 0; Rλ is -CI. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CF3. h another embodiment, n, p, and m are 0; Rj is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CF3; and Rg is -H. hi another embodiment, n, p, and m are 0; Rj is -CI. x is 1; A is -C(O)-N(R4)-;
R4 is -H; R8 is -CF3; and Rg is -H.
In another embodiment, n, p, and m are 0; Rx is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -OCH2CH3. hi another embodiment, n, p, and m are 0; R is -CI. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -OCH2CH3.
In another embodiment, n, p, and m are 0; Rj is -CI -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -OCH2CH3; and Rg is -H.
In another embodiment, n, p, and m are 0; R} is -CI. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -OCH2CH3; and Rg is -H. In another embodiment, n, p, and m are 0; Rj is -CH3. x is 1 ; A is
-C(O)-N(R4)-; R4 is -H; and R8 and Rg are -H. h another embodiment, n, p, and m are 0; R, is -CH3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. hi another embodiment, n, p, and m are 0; Rt is -CH3. x is 1 ; A is
-C(O)-N(R4)-; R4 is -H; R8 is -halo; and Rg is -H. h another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0; R is -CH3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CH3. In another embodiment, n, p, and m are 0; Rl is -CH3. x is 1 ; A is
-C(O)-N(R4)-; R4 is -H; R8 is -CH3; and Rg is -H. In another embodiment, n, p, and m are 0; R, is -CH3. x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CF3.
In another embodiment, n, p, and m are 0; Rj is -CH3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CF3; and Rg is -H. In another embodiment, n, p, and m are 0; Rj is -CH3. x is 1 ; A is
-C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -OCH2CH3.
In another embodiment, n, p, and m are 0; Rj is -CH3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -OCH2CH3; and Rg is -H.
In another embodiment, n, p, and m are 0; Rj is -CF3. x is 1; A is -C(O)-N(R4)-; R4 is -H; and R8 and Rg are -H.
In another embodiment, n, p, and m are 0; Rj is -CF3. x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. hi another embodiment, n, p, and m are 0; Rj is -CF3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -halo; and Rg is -H. In another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, n, p, and m are 0; Rj is -CF3. x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CH3.
In another embodiment, n, p, and m are 0; Rt is -CF3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CH3; and Rg is -H.
In another embodiment, n, p, and m are 0; R} is -CF3. x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CF3. ha another embodiment, n, p, and m are 0; Rx is -CF3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CF3; and Rg is -H. In another embodiment, n, p, and m are 0; Rj is -CF3. x is 1 ; A is
-C(O)-N(R4)-; R4 is -H; R8 is -H; and g is -OCH2CH3.
In another embodiment, n, p, and m are 0; Rx is -CF3. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -OCH2CH3; and Rg is -H.
In another embodiment, n, p, and m are 0; R, is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -tert-butyl; and Rg is -H. In another embodiment, n, p, and m are 0; Rλ is -CI. x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -tert-butyl; and Rg is -H.
In another embodiment, n, p, and m are 0; Rl is R, is -CI -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -tert-butyl. In another embodiment, n, p, and m are 0; Rt is Rj is -CI. x is 1; A is -C(O)-
N(R4)-; R4 is -H; R8 is -H; and Rg is -tert-butyl.
In another embodiment, n, p, and m are 0; Rt is -CH3; x is 1; A is -C(O)- N(R4)-; R4 is -H; R8 is -tert-butyl; and Rg is -H.
In another embodiment, n, p, and m are 0; R, is -CH3; x is 1; A is -C(O)- N(R4)-; R4 is -H; R8 is -H; and Rg is -tert-butyl. hi another embodiment, n, p, and m are 0; Rj is -CH3; x is 1; A is -C(O)- N(R4)-; R4 is -H; R8 is -CH3; and Rg is -CH3.
In another embodiment, n is 0, Axx is -2-(3-nitropyridyl)-, m is 0, x is 0, and R8 and Rg are -H. In another embodiment, n is 0, Ax, is -2-(3-chloropyridyl)-, x is 1, A is -C(S)-
N(R4)-, m is 1, R3 is -CH3, R3 is attached to the carbon atom adjacent to the nitrogen attached to the -C(SO)-N(R4)- group, the carbon atom to which the R3 group is attached has the R configuration, R8 is -H, and Rg is -CH3.
In another embodiment, n and p are 0; m is 1; Rt is -CI, -Br, or -I. x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -Cl; x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0; m is 1; Rλ is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -halo. In another embodiment Rg is -CI. h another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R, is -CI x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -halo; and Rg is -H. i another embodiment R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CI, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. In another embodiment R8 is -CI. hi another embodiment, R8 is -Br. h another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; R1 is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R^ is -Cl; x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rλ is -CI x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R, is -CI x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R, is -CI, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rx is -CI, -Br, or -I. x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -OCH2CH3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rx is -CI, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, n and p are 0; m is 1; Rx is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration, h another embodiment, n and p are 0, m is 1, Rj is -CI, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, R! is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. In another embodiment, R, is -Br. another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, R! is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. hi another embodiment R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rλ is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R^^ is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Rx is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, hi another embodiment Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. In another embodiment R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rλ is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4 group, R8 is -H, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, R{ is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rx is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. hi another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rr is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, R, is -CF3, x is 1, A is -C(O)- N(R )-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0; m is 1; R, is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -tert-butyl; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration, hi another embodiment, n and p are 0, m is 1, Rj is -CI, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and R§ is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R: is -CI, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, R^ is -CH3, x is 1, A is -C(O)- N(R4)-, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -CH3, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n, p, and m are 0; R, is -CI, -Br, or, -I; x is 0; R4 is -H;
Figure imgf000051_0001
In another embodiment, n, p, and m are 0; Ri is -CI. x is 0; R4 is -H; and R8 and Rg are -H. hi another embodiment, n, p, and m are 0; Rt is -CI, -Br, or, -I; x is 0; R4 is -H;
R8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F.
In another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. hi another embodiment, Rg is -F. h another embodiment, n, p, and m are 0; R, is -CI, -Br, or, -I. x is 0; R4 is -H; R8 is -halo; and Rg is -H. In another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0; R: is -CI; x is 0; R4 is -H; R8 is - halo; and Rg is -H. h another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. h another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0; R, is -CI, -Br, or, -I. x is 0; R4 is -H;
Figure imgf000051_0002
hi another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H;
Figure imgf000051_0003
h another embodiment, n, p, and m are 0; Rx is -CI, -Br, or, -I; x is 0; R4 is -H;
Figure imgf000051_0004
In another embodiment, n, p, and m are 0; R, is -CI; x is 0; R4 is -H; R8 is
Figure imgf000051_0005
In another embodiment, n, p, and m are 0; R, is -CI, -Br, or, -I; x is 0; R4 is -H;
Figure imgf000051_0006
In another embodiment, n, p, and m are 0; R, is -CI; x is 0; R4 is -H; R8 is -H;
Figure imgf000052_0001
hi another embodiment, n, p, and m are 0; Rj is -CI, -Br, or, -I; x is 0; R is -H;
Figure imgf000052_0002
In another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is
Figure imgf000052_0003
In another embodiment, n, p, and m are 0; Rj is -CI, -Br, or, -I; x is 0; R4 is -H; R8 is -H; and Rg is -OCH2CH3. hi another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H;
Figure imgf000052_0004
In another embodiment, n, p, and m are 0; R{ is -CI, -Br, or, -I; x is 0; R4 is -H; R8 is -OCH2CH3; and Rg is -H.
In another embodiment, n, p, and m are 0; Rt is -CI; x is 0; R4 is -H; R8 is -OCH2CH3; and Rg is -H. hi another embodiment, n, p, and m are 0; Rλ is -CH3; x is 0; R4 is -H; and R8
Figure imgf000052_0005
hi another embodiment, n, p, and m are 0; R, is -CH3; x is 0; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. i another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, n, p, and m are 0; R, is -CH3; x is 0; R4 is -H; R8 is
-halo; and Rg is -H. In another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, n, p, and m are 0; Rj is -CH3; x is 0; R4 is -H; R8 is
Figure imgf000052_0006
In another embodiment, n, p, and m are 0; R{ is -CH3; x is 0; R4 is -H; R8 is
Figure imgf000052_0007
hi another embodiment, n, p, and m are 0; Rj is -CH3; x is 0; R4 is -H; R8 is
Figure imgf000052_0008
In another embodiment, n, p, and m are 0; R! is -CH3; x is 0; R4 is -H; R8 is -CF3; andRg is -H.
In another embodiment, n, p, and m are 0; Rj is -CH3; x is 0; R4 is -H; R8 is -Hj and Rg is -OCHjCH,.
In another embodiment, n, p, and m are 0, Rt is -CH3; x is 0; R4 is -H; R8 is
Figure imgf000053_0001
In another embodiment, n, p, and m are 0; Rλ is -CF3; x is 0; R4 is -H; and R8
Figure imgf000053_0002
In another embodiment, n, p, and m are 0; Rj is -CF3; x is 0; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. hi another embodiment, Rg is -F. hi another embodiment, n, p, and m are 0; Rl is -CF3; x is 0; R4 is -H; R8 is -halo; and Rg is -H. In another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. h another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0, Rj is -CF3; x is 0; R4 is -H; R8 is -H;
Figure imgf000053_0003
hi another embodiment, n, p, and m are 0; R, is -CF3; x is 0; R4 is -H; R8 is
Figure imgf000053_0004
In another embodiment, n, p, and m are 0; Rx is -CF3; x is 0; R4 is -H; R8 is -H;
Figure imgf000053_0005
hi another embodiment, n, p, and m are 0; R is -CF3; x is 0; R4 is -H; R8 is
Figure imgf000053_0006
hi another embodiment, n, p, and m are 0; Rj is -CF3; x is 0; R4 is -H; R8 is -H;
Figure imgf000053_0007
In another embodiment, n, p, and m are 0; R^^ is -CF3; x is 0; R4 is -H; R8 is
Figure imgf000053_0008
In another embodiment, n, p, and m are 0; Rj is -CI, -Br, or, -I; x is 0; R4 is -H; R8 is -tert-butyl; and Rg is -H.
In another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -tert- butyl; and Rg is -H.
In another embodiment, n, p, and m are 0; Rj is -CI, -Br, or, -I; x is 0; R4 is -H; R8 is -H; and Rg is -tert-butyl. In another embodiment, n, p, and m are 0; Rt is -CI; x is 0; R4 is -H; R8 is -H; and Rg is -tert-butyl. In another embodiment, n, p, and m are 0; Rλ is -CH3; x is 0; R4 is -H; R8 is -tert-butyl; and Rg is -H. h another embodiment, n, p, and m are 0; Rλ is -CH3; x is 0; R4 is -H; R8 is -H; and Rg is -tert-butyl. hi another embodiment, n, p, and m are 0; Rj is -CH3; x is 0; R4 is -H; R8 is
Figure imgf000054_0001
In another embodiment, n and p are 0; m is 1 ; R! is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1 ; Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1 ; Rλ is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -H; and Rg is -halo. In another embodiment Rg is -CI. In another embodiment, Rg is -Br. hi another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, R, is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. hi another embodiment, Rg is -Br. h another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; R! is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -halo; and Rg is -H. In another embodiment R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rx is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -halo, and R, is -H. In another embodiment R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, n and p are 0; m is 1; Rλ is -CI, -Br, or -I; x is 0; R4 is
-H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration.
In another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 0; R4 is
-H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; R^ is -CI, -Br, or -I; x is 0; R4 is
-H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, R1 is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Ri is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rx is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -halo, and Rg is -H. In another embodiment R8 is -CI. h another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rx is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -OCH2CH3, and R, is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, n and p are 0, m is 1, Rλ is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -halo, and Rg is -H. In another embodiment R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rλ is -CF3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R{ is -CF3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, R{ is -CF3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Ri is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -OCH2CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. i another embodiment, n and p are 0; m is 1; Rr is -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R4 is -H; R8 is -tert-butyl; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rλ is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, n and p are 0; m is 1; Rt is -CI, -Br, or, -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R4 is -H; R8 is -H; and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, R, is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, R! is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, Rg is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the
R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rt is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -CH3, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATJ is a pyridyl group, n is 0; m is 1; Rj is -CH3, -CI,
-Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A is a pyridyl group, n is 0, m is 1, R1 is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax is a pyridyl group; n is 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -Br. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, A is a pyridyl group, n is 0, m is 1, R, is -CI, x is 1,
A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Axl is a pyridyl group, n is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A is a pyrimidinyl group; p is 0; m is 1; Rt is -CH3, -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is - halo, h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, A x is a pyrimidinyl group, p is 0, m is 1, R! is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, A is a pyrimidinyl group; p is 0; m is 1; R^ is -CI,
-Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -Br. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, ATJ is a pyrimidinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and R, is -Br. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, A is a pyrimidinyl group, p is 0, m is 1, Rx is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Axλ is a pyridyl group; n is 0; m is 1; R^ is -CH3, -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R4 is -H; R8 is -H; and Rg is -halo, hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Art is a pyridyl group, n is 0, m is 1, Rx is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Axx is a pyridyl group; n is 0; m is 1; Rλ is -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R4 is -H; R8 is -H; and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax, is a pyridyl group, n is 0, m is 1, Rt is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax{ is a pyridyl group, n is 0, m is 1, Rt is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Axx is a pyrimidinyl group; p is 0; m is 1; Rl is -CH3, -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ax, is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, Ax, is a pyrimidinyl group; p is 0; m is 1; Rt is -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group; R4 is -H; R8 is -H; and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Art is a pyrimidinyl group, p is 0, m is 1, R, is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATJ is a pyrimidinyl group, p is 0, m is 1, R, is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and R, is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. In another embodiment, m is 1 and R3 is -(C C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration. hi another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. hi another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration. In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration.
In another embodiment, m is 1 and R3 is
Figure imgf000065_0001
and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the R configuration. In another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the S configuration. hi another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the S configuration.
4.2 The Compounds of Formula (lb)
The present invention also encompasses compounds of formula (lb):
Figure imgf000066_0001
(lb) and pharmaceutically acceptable salts thereof, where Axx, R3, R8, Rg, A, x, and m, are defined above for the Benzoazolylpiperazine Compounds of formula (lb), hi one embodiment, Ax, is a pyrazinyl group. In another embodiment, Aη is a pyridazinyl group. In another embodiment, Art is a thiazanyl group. In another embodiment, x is 1 and A is -C(O)-N(R4)-. hi another embodiment, x is 1 and A is -C(S)-N(R4)-. hi another embodiment x is 0.
In another embodiment, p is 0.
In another embodiment, p is 1. hi another embodiment, m is 0.
In another embodiment, m is 1.
In another embodiment, R4 is -H.
In another embodiment, R4 is -(CrC6)alkyl.
In another embodiment, Ax, is a pyrazinyl group, x is 1, and A is -C(O)N(R4)-
In another embodiment, ATJ is a pyrazinyl group, x is 1, and A is -C(S)N(R4)-,
In another embodiment, ATJ is a pyridazinyl group, x is 1, and A is -
C(O)N(R4)-
In another embodiment, Ax is a pyridazinyl group, x is 1, and A is - C(S)N(R4)-,
In another embodiment, Ax, is a thiazanyl group, x is 1, and A is -C(O)N(R4)-
In another embodiment, Ax, is a thiazanyl group, x is 1, and A is -C(S)N(R4)-.
In another embodiment, Rl is -H. hi another embodiment, Rj is -CI. hi another embodiment, Rλ is -Br.
In another embodiment, Rx is -I.
In another embodiment, Ri is -F.
In another embodiment, Rx is -(Cj-C^alkyl.
In another embodiment, Rt is -CH3.
In another embodiment, Rλ is -NO2.
In another embodiment, R, is -CN.
In another embodiment, R, is -OH. hi another embodiment, R, is -OCH3.
In another embodiment, R is -NH2.
In another embodiment, Rj is -C(halo)3. hi another embodiment, Rj is -CH(halo)2.
In another embodiment, R, is -CH2(halo).
In another embodiment, p is 1 and R2 is -halo, -CN, -OH,
Figure imgf000067_0001
-NO2, or -NH2.
In another embodiment, p is 1 and R2 is -(C C10)alkyl, -(C2-C10)alkenyl, -(C2- C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5- C10)cycloalkenyl,-(C8-C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
In another embodiment, p is 1 and R2 is -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups. In another embodiment, m is 1 and R3 is -halo, -CN, -OH, -O(CrC6)alkyl,
-NO2, or -NH2.
In another embodiment, m is 1 and R3 is -(Cι-C10)alkyl, -(C2-C10)alkenyl, -(C2- C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-C14)bicycloalkyl,
Figure imgf000068_0001
-(C5- C10)cycloalkenyl,-(C8-C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups.
In another embodiment, m is 1 and R3 is -phenyl, -naphthyl, -(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups. In another embodiment, R8 and Rg are each independently -H, halo, -(Cr
C6)alkyl, -O(CrC6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo).
In another embodiment, at least one of R8 or Rg is -H.
In another embodiment, p and m are 0, R is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. In another embodiment, p and m are 0, R, is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H.
In another embodiment, p and m are 0, Rx is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and R, is -halo. In another embodiment, g is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, p and m are 0, Rx is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, hi another embodiment, Rg is -CI. h another embodiment, Rg is -Br. In another embodiment, Rg is -F. hi another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. h another embodiment, p and m are 0, Rx is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. hi another embodiment, R8 is -F. In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -CH3.
In another embodiment, p and m are 0, R{ is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3.
In another embodiment, p and m are 0, R is -halo x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H.
In another embodiment, p and m are 0, R{ is -halo x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. h another embodiment, p and m are 0, Rλ is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. hi another embodiment, p and m are 0, Rj is -halo x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H.
In another embodiment, p and m are 0, R, is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H.
In another embodiment, p and m are 0, Rλ is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3.
In another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and g is -OCH2CH3. In another embodiment, p and m are 0, ^ is -halo, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -OCH2CH3, and Rg is -H. In another embodiment, p and m are 0, Rj is -CI x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H. hi another embodiment, p and m are 0, Rt is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. hi another embodiment, p and m are 0, Rλ is -CH3 x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. hi another embodiment, p and m are 0, Rj is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. hi another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. hi another embodiment, R8 is -F. hi another embodiment, p and m are 0, Rj is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and R§ is -CH3.
In another embodiment, p and m are 0, Rλ is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. In another embodiment, p and m are 0, R! is -CH3 x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and R, is -CF3.
In another embodiment, p and m are 0, Rj is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3.
In another embodiment, p and m are 0, Rx is -CH3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CF3 x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. hi another embodiment, p and m are 0, Rx is -CF3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. hi another embodiment, Rg is -F.
In another embodiment, p and m are 0, Rl is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. hi another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 s -H, R8 is -H, and Rg is -CH3.
In another embodiment, p and m are 0, Rλ is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. hi another embodiment, p and m are 0, R, is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. hi another embodiment, p and m are 0, R, is -CF3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H.
In another embodiment, p and m are 0, Rγ is -CF3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3.
In another embodiment, p and m are 0, Rj is -CF3 x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H. hi another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and R, is -H. h another embodiment, p and m are 0, R, is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H.
In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. hi another embodiment, p and m are 0, R1 is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl.
In another embodiment, p and m are 0, Rx is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. hi another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -CH3, and Rg is -CH3.
In another embodiment, p is 0, m is 1, R, is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, R, is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rx is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, hi another embodiment, Rg is -CI. In another embodiment, Rg is -Br. hi another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. In another embodiment, R8 is -Br. hi another embodiment, R8 is -F. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, R is -halo, x is 1, A is -C(O)-N(R )-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rt is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rt is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rx is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, Rg is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rλ is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rt is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, hi another embodiment R, is -CI. hi another embodiment, Rg is -Br. hi another embodiment, Rg is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rλ is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. hi another embodiment R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R{ is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rx is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. hi another embodiment R8 is -CI. In another embodiment, R8 is -Br. hi another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rr is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R{ is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rx is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rλ is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R )-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rλ is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -CH3, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p and m are 0, Rx is -halo x is 0, R4 is -H, and R8 and
hi another embodiment, p and m are 0, Rλ is -CI x is 0, R4 is -H, and R8 and Rg are -H.
In another embodiment, p and m are 0, R, is -halo x is 0, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, p and m are 0, Rλ is -CI, x is 0, R4 is -H, R8 is -H, and
Rg is -halo, hi another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F.
In another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, p and m are 0, Rx is -CI, x is 0, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, p and m are 0, R is -halo, x is 0, R4 is -H, R8 is -H,
Figure imgf000079_0001
In another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000079_0002
In another embodiment, p and m are 0, Rx is -halo, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000079_0003
In another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000079_0004
In another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -CF3. hi another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000080_0001
In another embodiment, p and m are 0, R, is -halo, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000080_0002
In another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000080_0003
In another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -OCH2CH3. hi another embodiment, p and m are 0, R, is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000080_0004
hi another embodiment, p and m are 0, R, is -halo, x is 0, R4 is -H, R8 is
Figure imgf000080_0005
In another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is
Figure imgf000080_0006
In another embodiment, p and m are 0, R, is -CH3, x is 0, R4 is -H, and R8 and
In another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -halo, hi another embodiment, Rg is -CI. In another embodiment, Rg is -Br. h another embodiment, Rg is -F.
In another embodiment, p and m are 0, R, is -CH3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. h another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. In another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000080_0007
In another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000080_0008
In another embodiment, p and m are 0, Rx is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000080_0009
hi another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000081_0001
hi another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -OCH2CH3. In another embodiment, p and m are 0, Rx is -CH3, x is 0, R4 is -H, R8 is
Figure imgf000081_0002
In another embodiment, p and m are 0, R! is -CF3, x is 0, R4 is -H, and R8 and
In another embodiment, p and m are 0, Rx is -CF3, x is 0, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, R, is -Br. In another embodiment, Rg is -F. hi another embodiment, p and m are 0, R, is -CF3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, p and m are 0, R is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000081_0003
In another embodiment, p and m are 0, R, is -CF3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000081_0004
In another embodiment, p and m are 0, Rx is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000081_0005
hi another embodiment, p and m are 0, R, is -CF3, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000081_0006
In another embodiment, p and m are 0, Rx is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000081_0007
In another embodiment, p and m are 0, Rt is -CF3, x is 0, R4 is -H, R8 is
Figure imgf000081_0008
In another embodiment, p and m are 0, R, is -halo, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. hi another embodiment, p and m are 0, Rx is -CI, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. In another embodiment, p and m are 0, Rλ is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl.
In another embodiment, p and m are 0, Rλ is -CI, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, p and m are 0, Rx is -CH3, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. hi another embodiment, p and m are 0, Rλ is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl.
In another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000082_0001
ha another embodiment, p is 0, m is 1, Rx is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rx is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rx is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rλ is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R] is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. h another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, R, is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rt is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R, is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rt is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R{ is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rλ is -CI, x is 0, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rλ is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, R, is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -halo, and Rg is -H. In another embodiment R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, Rg is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rt is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rx is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, Rg is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rλ is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, R is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -halo. In another embodiment Rg is -CI. In another embodiment,
Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. In another embodiment,
R8 is -Br. In one embodiment, R8 is -F. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, R} is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rx is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rx is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rl is -CF3, x is 0, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -tert-butyl, and R§ is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R{ is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, Rg is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rλ is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -CH3, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, A^ is a pyrazinyl group, p is 0, m is 1, Rx is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATJ is a pyrazinyl group, p is 0, m is 1, Rλ is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar! is a pyrazinyl group, p is 0, m is 1, Rλ is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Axx is a pyrazinyl group, p is 0, m is 1, Ri is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, Rg is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Axλ is a pyrazinyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar! is a pyridazinyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, A x is a pyridazinyl group, p is 0, m is 1, Ri is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ax{ is a pyridazinyl group, p is 0, m is 1, Rλ is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, AT] is a pyridazinyl group, p is 0, m is 1, R! is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A^ is a pyridazinyl group, p is 0, m is 1, R! is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar! is a thiazanyl group, p is 0, m is 1, Rx is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ax, is a thiazanyl group, p is 0, m is 1, Ri is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Axx is a thiazanyl group, p is 0, m is 1, Rl is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Aτι is a thiazanyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rλ is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ax, is a pyrazinyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax, is a pyrazinyl group, p is 0, m is 1, R is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -CI. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax, is a pyrazinyl group, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ax, is a pyrazinyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax{ is a pyrazinyl group, p is 0, m is 1, Ri is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A-Ci is a pyridazinyl group, p is 0, m is 1, Rl is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ax is a pyridazinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Aτι is a pyridazinyl group, p is 0, m is 1, R! is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Art is a pyridazinyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A^ is a pyridazinyl group, p is 0, m is 1, Ri is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -F. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ax, is a thiazanyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, A^ is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A^ is a thiazanyl group, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and R, is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, A^ is a thiazanyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATJ is a thiazanyl group, p is 0, m is 1, R, is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzothiazolyl group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, m is 1 and R3 is -(C1-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. ha another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. hi another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -(C1-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. hi another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0. hi another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzothiazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration.
In another embodiment, m is 1 and R3 is
Figure imgf000095_0001
and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or a thiazanyl group, ha another embodiment, m is 1 and R3 is -(C1-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or a thiazanyl group and the carbon to which the R3 group is attached is in the R configuration. , hi another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the R configuration. hi another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group, hi another embodiment, m is 1 and R3 is -(CrC4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the S configuration.
The present invention also encompasses compounds of formula (ha):
4.3 The Compounds of Formula (Ha)
Figure imgf000096_0001
(Ha) and pharmaceutically acceptable salts thereof, where Arl5 R3, R8, Rg, R10 and m, are defined above for the Benzoazolylpiperazine Compounds of formula (Ha). ha one embodiment, A^ is a pyridyl group.
In another embodiment, Ar, is a pyrimidinyl group. ha another embodiment, A^ is a pyrazinyl group. ha another embodiment, n or p is 0. ha another embodiment, n or p is 1. ha another embodiment, m is 0. ha another embodiment, m is 1. ha another embodiment, R10 is -H. ha another embodiment, R10 is -(CrC4)alkyl. ha another embodiment, R10 is -CH3. ha another embodiment, R, is -CI. ha another embodiment, Rx is -Br.
In another embodiment, Rλ is -I. ha another embodiment, Rλ is -( -C^alkyl. ha another embodiment, R, is -CH3. ha another embodiment, Rx is -NO2. ha another embodiment, Rj is -CN.
In another embodiment, R is -OH. ha another embodiment, R, is -OCH3. ha another embodiment, Rj is -NH2. In another embodiment, Rx is -C(halo)3. ha another embodiment, Rj is -CH(halo)2. ha another embodiment, Rj is -CH2(halo).
In another embodiment, n and p are 1 and R2 is -halo, -CN, -OH, -O(Cr C6)alkyl, -NO2, or -NH2. In another embodiment, n and p are 1 and R2 is -(C1-C10)alkyl, -(C2-
C10)alkenyl, -(C2-C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8- C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(Cg-C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, n and p are 1 and R2 is -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; ha another embodiment, m is 1 and R3 is -halo, -CN, -OH, -O(Cι-C6)alkyl, -NO2, or -NH2. ha another embodiment, m is 1 and R3 is -(C,-C10)alkyl, -(C2-C10)alkenyl, -(C2-
C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5- C10)cycloalkenyl,-(C8-C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, m is 1 and R3 is -phenyl, -naphthyl, -(C14)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups. hi another embodiment, Rg and Rg are each independently -H, halo, -(Cr C6)alkyl, -O(CrC6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo).
In another embodiment, at least one of R8 or R, is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R4 is -H; and R8
Figure imgf000098_0001
ha another embodiment, n, p, and m are 0; R, is -CI. R4 is -H; and R8 and Rg are -H. ha another embodiment, n, p, and m are 0; Rx is -CI -Br, or -I; R4 is -H; R8 is - halo H; and Rg is -H. ha another embodiment, Rg is -CI. a another embodiment, Rg is -Br. In another embodiment, Rg is -F.
In another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -halo; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rx is -CI, -Br, or -I; R4 is -H; R8 is - H; and Rg is -CH3. In another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. a another embodiment, Rg is -F. hi another embodiment, n, p, and m are 0; Ry is -CI. R4 is -H; R8 is -H; and Rg is -CH3. ha another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rr is -CI -Br, or -I; R4 is -H; R8 is -CH3; and Rg is -H. In another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rt is -CI. R4 is -H; R8 is -CH3; and Rg is -H. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rt is -CI, -Br, or -I; R4 is -H; R8 is - H; and Rg is -CF3. In another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -H; and Rg is -CF3. In another embodiment, Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. a another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R4 is -H; R8 is -CF3; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rl is -CI; R4 is -H; R8 is -CF3; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. a another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R4 is -H; R8 is
-H; and Rg is -OCH2CH3. hi another embodiment, Rg is -CI. In another embodiment, Rg is - Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R4 is -H; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is - Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R4 is -H; R8 is
Figure imgf000099_0001
ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -H; and Rg is -CH3. ha another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R4 is -H; R8 is
Figure imgf000099_0002
ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -CH3; and
ha another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R4 is -H; R8 is
Figure imgf000099_0003
ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -H; and Rg is -CF3. ha another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R4 is -H; R8 is
Figure imgf000100_0001
ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -CF3; and
a another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R4 is -H; R8 is
Figure imgf000100_0002
ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, n, p, and m are 0; Rj is -CI, Br, or -I; R4 is -H; R8 is
Figure imgf000100_0003
ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -OCH2CH3;
Figure imgf000100_0004
ha another embodiment, n, p, and m are 0, Rj is -CH3, R4 is -H, and R8 and Rg are -H.
ha another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F.
In another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -halo; and Rg is -H. In another embodiment, R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -H; and
Figure imgf000100_0005
ha another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -CH3; and
In another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -H; and
Figure imgf000100_0006
ha another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -CF3; and In another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -H; and
Figure imgf000101_0001
ha another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is
Figure imgf000101_0002
ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; and R8 and Rg are -H. ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is -halo; and
Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F.
In another embodiment, n, p, and m are 0; Rt is -CF3; R4 is -H; R8 is -H; and
Figure imgf000101_0003
ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is -CH3; and
ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is -H; and
Figure imgf000101_0004
hi another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is -CF3; and
ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is -H; and
Figure imgf000101_0005
ha another embodiment, n, p, and m are 0; Rj is -CF3; R4 is -H; R8 is
Figure imgf000101_0006
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R4 is -H; R8 is
-tert-butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -tert-butyl;
Figure imgf000101_0007
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; R4 is -H; R8 is -H; and Rg is -tert-butyl. hi another embodiment, n, p, and m are 0; Rj is -CI; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -tert- butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; Rx is -CH3; R4 is -H; R8 is -H; and
Rg is -tert-butyl. hi another embodiment, n, p, and m are 0; Rj is -CH3; R4 is -H; R8 is -CH3; and
Figure imgf000102_0001
ha another embodiment, n is 0, ATJ is -2-(3-chloropyridyl)-, m is 1, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, the carbon atom to which the R3 group is attached has the R configuration, R10 is -H, R8 is methyl, and R, is iso-propyl. ha another embodiment, n is 0, Arj is -2-(3-chloropyridyl)-, m is 1, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, the carbon atom to which the R3 group is attached has the R configuration, R10 is -H, R8 is ώo-propyl, and R, is methyl.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R8 is -H; and Rg is -halo, ha another embodiment Rg is -CI. hi another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -H; and Rg is -halo, h another embodiment Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -halo; and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0; m is 1 ; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -halo; and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. . ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R8 is -H; and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; R is -C1,;R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; R, is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the - benzoimidazole group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -benzoimidazole group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, Rg is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, n and p are 0, m is 1, R, is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -H, and R, is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -OCH2CH3, and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, R, is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -H, and Rg is -halo, i another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R8 is -CF3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -H, and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group; R4 is -H; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, R, is -CI, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group; R4 is -H; R8 is -H; and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CI, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R4 is -H, R8 is -H, and Rg is -tert-butyl. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazole group, R4 is -H, R8 is -tert-butyl, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, n and p are 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazole group, R4 is -H, R8 is -CH3, and Rg is -CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group; n is 0; m is 1; Rj is -CH3, -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group n is 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group; n is 0; m is 1; Rj is -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group; R4 is -H; R8 is -H; and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0, m is 1, Rj is -CI, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group; p is 0; m is 1; Rj is -CH3, -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group; p is 0; m is 1; Rj is -CI, -Br, or -I; R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R4 is -H; R8 is -H; and Rg is -Br. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, R, is -CI, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group; p is 0; m is 1; Rj is -CH3, -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R4 is -H; R8 is -H; and R, is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrazinyl group; p is 0; m is 1; Rj is -CI, -Br, or -I; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group; R4 is -H; R8 is -H; and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CI, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CH3, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzimidazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- or the benzothiazolyl group and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group, ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group and the carbon to which the R3 group is attached is in the R configuration, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group, ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group and the carbon to which the R3 group is attached is in the S configuration, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group, pyrimidinyl group, or pyrazinyl group and the carbon to which the R3 group is attached is in the S configuration.
4.4 The Compounds of Formula (lib) The present invention also encompasses compounds of formula (lib):
Figure imgf000114_0001
(nb) and pharmaceutically acceptable salts thereof, where Arj, R3, R8, Rg, A, x, and m, are defined above for the Benzoazolylpiperazine Compounds of formula (fib). ha one embodiment, Arj is a pyridazinyl group. ha another embodiment, Ar j is a thiazanyl group. ha another embodiment, x is 1 and A is -C(O)-N(R4)-. ha another embodiment, x is 1 and A is -C(S)-N(R4)-. ha another embodiment x is 0. ha another embodiment, x is 1. ha another embodiment p is 0. ha another embodiment, p is 1. ha another embodiment m is 0. ha another embodiment, m is 1. ha another embodiment, R4 is -H. ha another embodiment, R4 is -(Cj-C6)alkyl.
In another embodiment, R10 is -H.
In another embodiment, R10 is -(Cj-C4)alkyl. ha another embodiment, Rj0 is -CH3. ha another embodiment, Arj is a pyrazinyl group, x is 1, and A is -C(O)N(R4)-. In another embodiment, Arj is a pyrazinyl group, x is 1, and A is -C(S)N(R4)-. hi another embodiment, Ar, is a thiazanyl group, x is 1, and A is -C(O)N(R4)-. ha another embodiment, Arj is a thiazanyl group, x is 1, and A is -C(S)N(R4)-. hi another embodiment, Rj is -H.
In another embodiment, Rx is -CI.
In another embodiment, Rj is -Br. hi another embodiment, Rj is -I.
In another embodiment, Rj is -F. ha another embodiment, Rj is -(Cj-C6)alkyl. ha another embodiment, R, is -CH3. ha another embodiment, Rj is -NO2. ha another embodiment, Rj is -CN. ha another embodiment, Rj is -OH. ha another embodiment, Rj is -OCH3. ha another embodiment, Rj is -NH2. ha another embodiment, Rj is -C(halo)3. ha another embodiment, Rj is -CH(halo)2. ha another embodiment, Rj is -CH2(halo). ha another embodiment, p is 1 and R2 is -halo, -CN, -OH, -O(Cj-C6)alkyl, -NO2, or -NH2. ha another embodiment, p is 1 and R2 is -(Cj-Cι0)alkyl, -(C2-C10)alkenyl, -(C2- C10)alkynyl, -(C3-C10)cycloalkyl, -(C8-Cj4)bicycloalkyl, -(C8-Cι4)tricycloalkyl, -(C5- Cj0)cycloalkenyl,-(C8-Cj4)bicycloalkenyl, -(C8-Cj4)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, p is 1 and R2 is -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; ha another embodiment, m is 1 and R3 is -halo, -CN, -OH, -O(Cj-C6)alkyl, -NO2, or -NH2. ha another embodiment, m is 1 and R3 is -(Cj-C10)alkyl, -(C2-C10)aιkenyl, -(C2- Cj0)alkynyl, -(C3-Cj0)cycloalkyl, -(C8-C14)bicycloalkyl, -(Cg-Ci4)tricycloalkyl, -(C5- Cj0)cycloalkenyl,-(C8-Cj4)bicycloalkenyl, -(C8-Cj4)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, m is 1 and R3 is -phenyl, -naphthyl, -(Cj4)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups. ha another embodiment, R8 and Rg are each independently -H, halo, -(Cr C6)alkyl, -O(Cj-C6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo). ha another embodiment, at least one of R8 or Rg is -H. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. hi another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. a another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. h another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. h another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. hi another embodiment, R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F. h another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and R, is -CH3.
In another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and R, is -H. a another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and g is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H.
In another embodiment, p and m are 0, Rt is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, a another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rt is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. hi another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. hi another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. a another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F.
In another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F.
In another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -CH3.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. a another embodiment, R8 is -Br. hi another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R, is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. hi another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. hi another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and R§ is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rt is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rt is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4>, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R )-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and R, is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -CH3, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, and R8 and
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. a another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -halo, and Rg is -H. h another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. In another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H,
Figure imgf000127_0001
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000127_0002
h another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000127_0003
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000127_0004
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H,
Figure imgf000127_0005
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000127_0006
h another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000127_0007
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000127_0008
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000128_0001
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is
Figure imgf000128_0002
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is
Figure imgf000128_0003
h another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, and R8 and
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000128_0004
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000128_0005
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000128_0006
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000128_0007
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000128_0008
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is
Figure imgf000128_0009
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, and R8 and
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, R, is -F. ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000129_0001
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000129_0002
a another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000129_0003
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000129_0004
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000129_0005
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -
Figure imgf000129_0006
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, R, is -CH3, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000129_0007
ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R8 and Rg are -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and R, is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. In another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. a another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CF3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CF3, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, Rg is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -OCH2CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, Rg is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. ha another embodiment,
Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. a another embodiment,
R8 is -Br. hi another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, Rg is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, R, is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R, is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R8 is -OCH2CH3, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -CH3, and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, R, is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridazinyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, R, is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridazinyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -halo, a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -CI. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, R, is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -CI. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a thiazanyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzoimidazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0. In another embodiment, m is 1 and R3 is -(Cι-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0. hi another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzoimidazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration. a another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group, ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group, ha another embodiment, m is 1 and R3 is -(C j-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R3 group is attached is in the S configuration. hi another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridazinyl group or thiazanyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyridazinyl group or thiazanyl group and the carbon to which the R3 group is attached is in the S configuration. 4.5 The Compounds of Formula (Ilia)
The present invention encompasses compounds of Formula (-Ha)
Figure imgf000142_0001
(Hla) and pharmaceutically acceptable salts thereof, where Arj, R3, R8, Rg, A, x, and m, are defined above for the Benzoazolylpiperazine Compounds of formula (Hla). ha one embodiment, Arj is a pyridyl group. ha another embodiment, Arj is a pyrimidinyl group. ha another embodiment, x is 1 and A is -C(O)-N(R4)-. ha another embodiment, x is 1 and A is -C(S)-N(R4)-. ha another embodiment x is 0. ha another embodiment x is 1. ha another embodiment n or p is 0. ha another embodiment n or p is 1. ha another embodiment m is 0. a another embodiment m is 1. ha another embodiment, Arj is a pyridyl group, x is 1, and A is -C(O)N(R4)-. ha another embodiment, Arj is a pyridyl group, x is 1, and A is -C(S)N(R4)-. ha another embodiment, Arj is a pyrimidinyl group, x is 1, and A is -
C(O)N(R4)- ha another embodiment, Arj is a pyrimidinyl group, x is 1, and A is
C(S)N(R4)- ha another embodiment, Rj is -CI.
In another embodiment, Rj is -Br. hi another embodiment, Rj is -I. ha another embodiment, Rj is -(Cj-C6)alkyl. ha another embodiment, Rj is -CH3.
In another embodiment, Rj is -NO2. ha another embodiment, Rj is -CN. ha another embodiment, Rj is -OH. ha another embodiment, Rj is -OCH3. hi another embodiment, Rj is -NH2.
In another embodiment, Rj is -C(halo)3. ha another embodiment, Rj is -CH(halo)2.
In another embodiment, Rj is -CH2(halo).
In another embodiment, n and p are 1 and R2 is -halo, -CN, -OH, -O(Cj- C6)alkyl, -NO2, or -NH2. a another embodiment, n and p are 1 and R2 is -(Cj-C10)alkyl, -(C2- Cjo)alkenyl, -(C2-Cj0)alkynyl, -(C3-C10)cycloalkyl, -(C8-Cj4)bicycloalkyl, -(C8- Cj4)tricycloalkyl, -(C5-Cι0)cycloalkenyl,-(C8-Cj4)bicycloalkenyl, -(C8-Cι4)fricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, n and p are 1 and R2 is -phenyl, -naphthyl, -(Cj4)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; ha another embodiment, m is 1 and R3 is -halo, -CN, -OH, -O(Cj-C6)alkyl, -NO2, or -NH2.
In another embodiment, m is 1 and R3 is -(Cj-Cj0)alkyl, -(C2-Cj0)alkenyl, -(C2- Cjo)alkynyl, -(C3-Cj0)cycloalkyl, -(C8-Cj4)bicycloalkyl, -(C8-Cι4)tricycloalkyl, -(C5- Cj0)cycloalkenyl,-(C8-Cj4)bicycloalkenyl, -(C8-Cj4)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. In another embodiment, m is 1 and R3 is -phenyl, -naphthyl, -(Cι4)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups. ha another embodiment, R4 is -H. ha another embodiment, R4 is -(Cj-C6)alkyl. ha another embodiment, R8 and Rg are each independently -H, halo, -(Cj- C6)alkyl, -O(Cj-C6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo). ha another embodiment, at least one of R8 or Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; and R8 and Rg are -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; and R8 and Rg are -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. hi another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -halo, a another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1 ; A is - C(O)-N(R4)-; R4 is -H; R8 is -halo; and Rg is -H. ha another embodiment, R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -halo; and Rg is -H. ha another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. hi another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is
-C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CH3. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -CH3. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -CH3; and Rg is -H. In another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CH3; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H, R8 is -H; and Rg is -CF3. hi another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-;
R4 is -H; R8 is -H; and Rg is -CF3. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CF3; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -CF3; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is
-C(O)-N(R4)-; R4 is -H; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4 , R4 is -H, and R8 and Rg are -H. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. ha another embodiment, R, is -F. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H.
In another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3.
In another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H. a another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is
-C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. hi another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. hi another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. in another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is
-C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3.
In another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. hi another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H.
In another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -tert-butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-;
R4 is -H; R8 is -tert-butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 1; A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0; Rj is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4 , R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -CH3. ha another embodiment, n is 0, Arj is -2-(3-nifropyridyl)-, m is 0, x is 0, and R8
Figure imgf000147_0001
In another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; and R8 and Rg are -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1, Rj is -CI; x is 1, A is -C(O)- N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -halo, ha another embodiment Rg is - CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; j is -CI; x is 1; A is -C(O)- N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -halo, ha another embodiment g is -CI. a another embodiment, Rg is -Br. a another embodiment, R, is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -halo; and Rg is -H. ha another embodiment R8 is - CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)-
N(R )-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -halo; and Rg is -H. ha another embodiment R8 is -CI. h another embodiment, R8 is -Br. hi another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rt is -CI; x is 1; A is -C(O)- N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 1 ; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -CH3; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R4)-; R4 is -H; R3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration, hi another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R )-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, n and p are 0; m is 1 ; Rx is -CI; x is 1 ; A is -C(O)-
N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is
-C(O)-N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R8 is -OCH2CH3; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; Rj is -CI; x is 1 ; A is -C(O)-
N(R4)-; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; Rg is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and R, are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and R, is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, and R8 and R, are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, h another embodiment R, is -CI. h another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rt is -CF3, x is 1, A is -C(O)-
N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, R1 is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and R, is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 1, A is -C(O)- N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -tert-butyl; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0; m is 1; Rj is -CI; x is 1; A is -C(O)- N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, Rg is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 1, A is -C(O)- N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -CH3, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H; and R8 and Rg are -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; and R8
Figure imgf000155_0001
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H;
R8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. h another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; R, is -CI, -Br, or -I; x is 0; R4 is -H; R8 is -halo; and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. hi another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0; Rj is -CI, x is 0; R4 is -H; R8 is -halo; and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H;
Figure imgf000155_0002
ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H;
Figure imgf000155_0003
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H;
Figure imgf000155_0004
ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is
Figure imgf000155_0005
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H;
Figure imgf000155_0006
ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H;
Figure imgf000155_0007
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H;
Figure imgf000155_0008
ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -CF3; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H;
Figure imgf000156_0001
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is
Figure imgf000156_0002
ha another embodiment, n, p, and m are 0; Rj is -CH3, x is 0; R4 is -H, and R8
Figure imgf000156_0003
ha another embodiment, n, p, and m are 0; Rj is -CH3, x is 0; R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0; Rj is -CH3, x is 0; R4 is -H, R8 is
-halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0; Rj is -CH3, x is 0; R4 is -H, R8 is -H,
Figure imgf000156_0004
ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -
Figure imgf000156_0005
ha another embodiment, n, p, and m are 0, Rx is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000156_0006
ha another embodiment, n, p, and m are 0, R, is -CH3, x is 0, R4 is -H, R8 is
Figure imgf000156_0007
ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000156_0008
ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -OCH2CH3, and Rg is -H. In another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, and R8
Figure imgf000156_0009
ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000157_0001
ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is
Figure imgf000157_0002
ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000157_0003
ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is
Figure imgf000157_0004
ha another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000157_0005
In another embodiment, n, p, and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is
Figure imgf000157_0006
ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R8 is -tert-butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -tert- butyl; and Rg is -H. ha another embodiment, n, p, and m are 0; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0; Rj is -CI; x is 0; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -tert-butyl, and Rg is -H. a another embodiment, n, p, and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, n, p, and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is
Figure imgf000158_0001
a another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; and R8 and Rg are -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1, Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -halo. In another embodiment Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment Rg is -CI. a another embodiment, Rg is -Br. a another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -halo; and Rg is -H. In another embodiment R8 is -CI. ha another embodiment, R8 is -Br. a another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1, Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment R8 is -CI. hi another embodiment, R8 is -Br. a another embodiment, R8 is -F. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1, Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R8 is -CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p 0; m is 1; Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -CF3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R4 is -H; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is
-CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -halo, and Rg is -H. hi another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -halo, a another embodiment Rg is -CI. h another embodiment, Rg is -Br. ha another embodiment, R, is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1 ; Rj is -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R4 is -H, R8 is -tert-butyl, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R4 is -H; R8 is -tert-butyl; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0; m is 1; Rj is -CI; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R4 is -H; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -tert-butyl, and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, n and p are 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -CH3, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group; n is 0; m is 1; Rj is -CH3, -CI, -Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Ar, is a pyridyl group, n is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyridyl group; n is 0; m is 1; Rj is -CI, -Br, or
-I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Ar, is a pyridyl group, n is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyridyl group, n is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyrimidinyl group; p is 0; m is 1; Rx is -CH3, -CI, -Br, -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, Arj is a pyrimidinyl group; p is 0; m is 1; Rj is -CI,
-Br, or -I; x is 1; A is -C(O)-N(R4)-; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group; R4 is -H; R8 is -H; and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. hi another embodiment, Arj is a pyridyl group; n is 0; m is 1; Rj is -CH3, -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyridyl group, n is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -CI. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. a another embodiment, Arj is a pyridyl group; n is 0; m is 1; Rj is -CI, -Br, or
-I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R4 is -H; R8 is -H; and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. hi another embodiment, Arj is a pyridyl group, n is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyridyl group, n is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration.
In another embodiment, Arj is a pyrimidinyl group; p is 0; m is 1; Rj is -CH3, -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group; R4 is -H; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and R, is -CI. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyrimidinyl group; p is 0; m is 1; Rj is -CI, -Br, or -I; x is 0; R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group; R4 is -H; R8 is -H; and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and R§ is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group. In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group, ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group and the carbon to which the R3 group is attached is in the S configuration.
In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- or the benzooxazolyl group and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group or pyrimidinyl group, hi another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group or pyrimidinyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group or pyrimidinyl group. In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the pyridyl group or pyrimidinyl group and the carbon to which the R3 group is attached is in the S configuration.
4.6 The Compounds of Formula (Mb)
The present invention also encompasses compounds of formula (ITIb):
Figure imgf000169_0001
(mb) and pharmaceutically acceptable salts thereof, where Arl5 R3, R8, Rg, A, x, and m, are defined above for the Benzoazolylpiperazine Compounds of formula (ITIb). ha one embodiment, Arj is a pyrazinyl group. ha another embodiment, Ar, is a pyridazinyl group. ha another embodiment, Arj is a thiazanyl group.
In another embodiment, x is 1 and A is -C(O)-N(R4)-. In another embodiment, x is 1 and A is -C(S)-N(R4)-. ha another embodiment x is 0. ha another embodiment, x is 1. ha another embodiment, p is 0.
In another embodiment, p is 1. ha another embodiment, m is 0. ha another embodiment, m is 1. ha another embodiment, Arj is a pyrazinyl group, x is 1, and A is -C(O)N(R4)- ha another embodiment, Arj is a pyrazinyl group, x is 1, and A is -C(S)N(R4)-. ha another embodiment, Arj is a pyridazinyl group, x is 1, and A is -C(O)N(R4)-. In another embodiment, Arj is a pyridazinyl group, x is 1, and A is
-C(S)N(R4)-. a another embodiment, Arj is a thiazanyl group, x is 1, and A is -C(O)N(R4)-.
In another embodiment, Arj is a thiazanyl group, x is 1, and A is -C(S)N(R4)-. ha another embodiment, Rj is -H. ha another embodiment, Rj is -CI. ha another embodiment, R, is -Br.
In another embodiment, R, is -I. a another embodiment, Rj is -F. a another embodiment, Rj is -(Cj-C6)alkyl. In another embodiment, Rj is -CH3.
In another embodiment, Rj is -NO2.
In another embodiment, Rj is -CN. ha another embodiment, Rj is -OH. hi another embodiment, R, is -OCH3. a another embodiment, Rj is -NH2. ha another embodiment, Rj is -C(halo)3. ha another embodiment, Rj is -CH(halo)2. a another embodiment, Rj is -CH2(halo). a another embodiment, p is 1 and R2 is -halo, -CN, -OH, -O(Cj-C6)alkyl, -NO2, or -NH2. In another embodiment, p is 1 and R2 is -(Cj-Cj0)alkyl, -(C2-C10)alkenyl, -(C2- Cjo)alkynyl, -(C3-Cj0)cycloalkyl, -(C8-Cι4)bicycloalkyl, -(C8-Ci4)tricycloalkyl, -(C5- Cj0)cycloalkenyl,-(C8-Cj4)bicycloalkenyl, -(Cg-C14)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rj groups. ha another embodiment, p is 1 and R2 is -phenyl, -naphthyl, -(Cj4)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; ha another embodiment, m is 1 and R3 is -halo, -CN, -OH, -O(Cj-C6)alkyl, -NO2, or -NH2. ha another embodiment, m is 1 and R3 is -(Cj-Cj0)alkyl, -(C2-C10)alkenyl, -(C2- C10)alkynyl, -(C3-Cj0)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-Cj4)tricycloalkyl, -(C5- Cj0)cycloalkenyl,-(C8-Cj4)bicycloalkenyl, -(C8-Ci4)tricycloalkenyl, -(3- to 7- membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, m is 1 and R3 is -phenyl, -naphthyl, -(Cj4)aryl or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups. ha another embodiment, R4 is -H. ha another embodiment, R4 is -(Cj-C6)alkyl. a another embodiment, R8 and Rg are each independently -H, halo, -(Cj- C6)alkyl, -O(Cj-C6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo). ha another embodiment, at least one of R8 or Rg is -H. ha another embodiment, p and m are 0, Rt is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, R, is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, g is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. hi another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, R, is -CI. ha another embodiment, Rg is -Br. ha another embodiment, R, is -F.
In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. hi another embodiment, R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F.
In another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CF3.
In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. hi another embodiment, Rg is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. In another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, and R8 and Rg are -H. In another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. a another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -CH3. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -H, and Rg is -CF3. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -CF3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. hi another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. hi another embodiment, p and m are 0, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R8 is -H, and Rg is -tert-butyl. a another embodiment, p and m are 0, Rj is -CH3, x is 1, A is -C(O)-N(R4)-,
R4 is -H, R8 is -CH3, and Rg is -CH3. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and R, is -halo, ha another embodiment, R is -CI. In another embodiment, Rg is -Br. In another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, h another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. hi another embodiment, Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. In another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. hi another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, R, is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, R, is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rx is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 1, A is -C(O)-N(R4)-, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)- N(R4)- group, R4 is -H, Rg is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)- N(R4)- group, R4 is -H, R8 is -CH3, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, and R8 and
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, and R8 and Rg are -H. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Rg is -halo, hi another embodiment, R, is -CI. ha another embodiment, Rg is -Br. a another embodiment, R, is -F. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H,
Figure imgf000182_0001
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000182_0002
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000182_0003
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000182_0004
In another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H,
Figure imgf000183_0001
In another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000183_0002
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000183_0003
a another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000183_0004
In another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H,
Figure imgf000183_0005
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and
Figure imgf000183_0006
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is
Figure imgf000183_0007
ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is
Figure imgf000183_0008
In another embodiment, p and m are 0, R, is -CH3, x is 0, R4 is -H, and R8 and
ha another embodiment, p and m are 0, R, is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. In another embodiment, Rg is -Br. ha another embodiment, Rg is -F. h another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000183_0009
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CH3, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H,
Figure imgf000183_0010
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000184_0001
ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is
Figure imgf000184_0002
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, and R8 and
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H, and Rg is -halo. In another embodiment, Rg is -CI. hi another embodiment, Rg is -Br. ha another embodiment, Rg is -F. ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000184_0003
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000184_0004
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000184_0005
hi another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -CF3,
Figure imgf000184_0006
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is -H,
Figure imgf000184_0007
ha another embodiment, p and m are 0, Rj is -CF3, x is 0, R4 is -H, R8 is
Figure imgf000184_0008
ha another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H. a another embodiment, p and m are 0, Rj is -halo, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CI, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rx is -CH3, x is 0, R4 is -H, R8 is -tert- butyl, and Rg is -H.
In another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, p and m are 0, Rj is -CH3, x is 0, R4 is -H, R8 is -CH3,
Figure imgf000185_0001
ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. ha another embodiment, Rg is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -halo, ha another embodiment, Rg is -CI. ha another embodiment, Rg is -Br. In another embodiment, Rg is -F. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -halo, and Rg is -H. In another embodiment, R8 is -CI. ha another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -halo, and Rg is -H. ha another embodiment, R8 is -CI. ha another embodiment, R8 is - Br. hi another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and R, is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. hi another embodiment, Rg is -Br. In another embodiment, Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. In another embodiment, R8 is -Br. ha another embodiment, R8 is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -OCH2CH3, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -halo, ha another embodiment Rg is -CI. ha another embodiment,
Rg is -Br. ha another embodiment, Rg is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -halo, and Rg is -H. ha another embodiment R8 is -CI. ha another embodiment,
R8 is -Br. ha another embodiment, R8 is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -CF3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R8 is -H, and Rg is -OCH2CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, p is 0, m is 1, Rj is -CF3, x is 0, R4 is -H, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R8 is -OCH2CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH, and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration ha another embodiment, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -tert-butyl, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -CH3, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, Rg is -H, and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridazinyl group, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridazinyl group, p is 0, m is 1, R, is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, R, is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -halo, a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -CI. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -halo, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CI, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 1, A is -C(O)-N(R4)-, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- group, R4 is -H, R8 is -H, and Rg is -F. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrazinyl group, p is 0, m is 1, R, is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrazinyl group, p is 0, m is 1, Rt is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, Rg is -H, and Rg is -Br. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrazinyl group, p is 0, m is 1, R, is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -Br. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrazinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -CI. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridazinyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3 or -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -halo, hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, R, is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -CI. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -halo, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and R§ is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CI, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, R8 is -H, and Rg is -Br. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a thiazanyl group, p is 0, m is 1, Rj is -CH3, x is 0, R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the benzooxazolyl group, R4 is -H, Rg is -H, and R, is -F. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0. In another embodiment, m is 1 and R3 is -CH, and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0 and the carbon to which the R3 group is attached is in the R configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nitrogen attached to the -C(O)-N(R4)- when x is 1 or the benzooxazolyl group when x is 0 and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nitrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group. In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the R configuration. In another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the R configuration.
In another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group, h another embodiment, m is 1 and R3 is -(Cj-C4)alkyl and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the S configuration. ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group, ha another embodiment, m is 1 and R3 is -CH3 and is attached to the carbon atom adjacent to the nifrogen attached to the pyrazinyl group, pyridazinyl group, or thiazanyl group and the carbon to which the R3 group is attached is in the S configuration.
4.7 The Compounds of Formula (IVa)
The present invention also encompasses compounds of formula (INa):
Figure imgf000199_0001
(INa) and pharmaceutically acceptable salts thereof, where ATj, Ar2, and R3, are defined above for the Benzoazolylpiperazine Compounds of formula (INa). ha one embodiment, ATj is a pyridyl group. In another embodiment, Arj is a pyrimidinyl group. ha another embodiment, Ar2 is a benzothiazolyl group, ha another embodiment, Ar2 is a benzooxazolyl group, ha another embodiment, Ar2 is a benzoimidazolyl group, ha another embodiment, n or p is 0. ha another embodiment, n or p is 1. ha another embodiment, Rj is -CI. ha another embodiment, Rj is -Br. ha another embodiment, Rj is -I. ha another embodiment, Rj is -F. ha another embodiment, Rj is -(Cj-C6)alkyl. ha another embodiment, Rj is -CH3. hi another embodiment, Rj is -NO2. ha another embodiment, Rj is -CN. ha another embodiment, Rj is -OH. ha another embodiment, Rj is -OCH3. ha another embodiment, Rj is -NH2. a another embodiment, Rj is -C(halo)3. ha another embodiment, Rj is -CH(halo)2. ha another embodiment, Rj is -CH2(halo). ha another embodiment, n and p are 1 and R2 is -halo, -CN, -OH, -O(Cj- C6)alkyl, -NO2, or -NH2.
In another embodiment, n and p are 1 and R2 is -(Cj-C10)alkyl, -(C2- Cj0)alkenyl, -(C2-Cio)alkynyl, -(C3-Cj0)cycloalkyl, -(C8-Cι4)bicycloalkyl, -(C8- Cj4)tricycloalkyl, -(C3-Cι0)cycloalkenyl,-(C8-Cι4)bicycloalkenyl, -(C8-Ci4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups. ha another embodiment, n and p are 1 and R2 is -phenyl, -naphthyl, -(Cj4)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; ha another embodiment, R3 is -H. ha another embodiment, R3 is -CH3. ha another embodiment, R8 and Rg are each independently -H, halo, -(Cj- C6)alkyl, -O(Cj-C6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo). ha another embodiment, at least one of R8 and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or, -I; ; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rt is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; Rg is -chloro; and Rg is -H. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. hi another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo, and Rg is -H. hi another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -fluoro, and Rg is -H. hi another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; ; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H, and Rg is -CH3. a another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, Ar l is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI -
Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3.
In another embodiment, Ar j is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. a another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. hi another embodiment Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and R§ is -H. h another embodiment, ATj Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is Rj is -F, -
CI -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -H; Rj is Rj is -F. Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or, -I; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI,
-Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro, and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -fluoro, and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; ; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI,
-Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3, and R, is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and R§ is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is R, is -
F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is Rj is -
F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A^ is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or, -I; ; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group, and R8 and Rg are -H. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo. In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F,
Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, Art is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; R, is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. hi another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H.
In another embodiment, A^ is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -fluoro, and Rg is -H. In another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; j is -F;
Ar2 is a benzothiazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; ; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, Ar t is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3, and Rg is -H. In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; R, is -F. Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F;
Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. h another embodiment, Arj Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is - F. Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and R, is -H. hi another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is Rj is
-F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is Rj is -F. Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; R, is - F, -CI, -Br, or, -I; ; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -CH3; R, is -F. Ar2 is a benzothiazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -CH3; R, is -F, -CI -Br, or -I; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; Rg is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Afj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F;
Ar2 is a benzothiazolyl group; R8 is -fluoro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; ; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F. Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
-CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rt is -F; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or, -I; ; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group, and R8 and Rg are -H. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rt is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, AJj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -fluoro, and Rg is -H. a another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; ; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -CF3. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and R§ is -H. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment Ar, is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj ATJ is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzoimidazolyl group; Rg is -tert-butyl; and Rg is -H. h another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is Rj is -F, -
CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Ar t is a pyridyl group, n is 0; R3 is -H; Rj is Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or, -I; ; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; Rj is -F. Ar2 is a benzoimidazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and g is -chloro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, AJ-J is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arx is a pyridyl group, n is 0; R3 is -CH3; Rx is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -fluoro, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI,
-Br, or -I; ; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment Ar, is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI,
-Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; R, is -F; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; R, is -F; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; R, is R, is - F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is Rt is - F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or, -I; ; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group, and R8 and R, are -H.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F,
Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. h another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -iodo. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and R, is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, Art is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. h another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo, and R is -H. h another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F;
Ar2 is a benzoimidazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -fluoro, and Rg is -H. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo, and Rg is -H.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; ; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H, and R, is -CH3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CH3; and R, is -H.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. hi another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Ajj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F.
Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj Ar J is a pyrimidinyl group, p is 0; R3 is -H; Rj is - F. Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is - F, -CI -Br, or, -I; ; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F. Ar2 is a benzoimidazolyl group, and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ai-j is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and R is -bromo. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -CH3; R, is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F;
Ar2 is a benzoimidazolyl group; R8 is -fluoro, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; ; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F. Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
-CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F;
Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Afj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rt is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzoimidazolyl group; Rg is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or, -I; ; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, Ar, is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro, and Rg is -H.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; R, is -F; Ar2 is a benzooxazolyl group; Rg is -iodo, and Rg is -H. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -H; R, is -F, -CI, - Br, or -I; ; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI -
Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and'Rg is -CF3. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -H; R, is -F. Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -H; R, is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. In another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rx is -F. Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment Ar j is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj ATJ is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is -F, -CI -
Br, or -I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -H; Rj is -F. Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -H; Rj is Rj is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Art is a pyridyl group, n is 0; R3 is -H; Rj is Rj is -F. Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or, -I; ; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F. Ar2 is a benzooxazolyl group, and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; R, is -F, -CI,
-Br, or -I; Ar2 is a benzooxazolyl group; Rg is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; ; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3, and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, fj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F. Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI,
-Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; R, is -F; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment A^ is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F, -CI,
-Br, or -I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is -F; R8 is -tert-butyl; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is Rj is - F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R3 is -CH3; Rj is Rj is - F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or, -I; ; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F;
Ar2 is a benzooxazolyl group, and R8 and Rg are -H. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F,
Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; R, is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; R, is -F, -
CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; R, is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; R, is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -halo, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F;
Ar2 is a benzooxazolyl group; R8 is -bromo, and Rg is -H. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro, and Rg is -H.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; ; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3, and Rg is -H. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F. Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F.
Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -OCH2CH3. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, - CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj ATJ is a pyrimidinyl group, p is 0; R3 is -H; Rj is - F. Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F, -
CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is -F. Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -H; Rj is Rj is -F. Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is - F, -CI, -Br, or, -I; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F. Ar2 is a benzooxazolyl group, and R8 and Rg are -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -CH3; R, is -F, Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R3 is -CH3; R, is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -halo; and R§ is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rt is -F; Ar2 is a benzooxazolyl group; R8 is -halo, and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F;
Ar2 is a benzooxazolyl group; R8 is -chloro, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rt is -F; Ar2 is a benzooxazolyl group; R8 is -bromo, and g is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro, and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -iodo, and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
-CI, -Br, or -I; ; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Art is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F;
Ar2 is a benzooxazolyl group; R8 is -H, and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; Rg is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3, and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F. Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, AJj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F,
-CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F;
Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment Ar j is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and R§ is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is -F; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R3 is -CH3; Rj is Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
4.8 The Compounds of Formula (IVb)
The present invention also encompasses compounds of formula (INb):
Figure imgf000242_0001
(INb) and pharmaceutically acceptable salts thereof, where Arl5 Ar2, A, R3 and x are defined above for the Benzoazolylpiperazine Compounds of formula (INb). ha one embodiment, Arj is a pyridyl group. ha another embodiment, Arj is a pyrimidinyl group. ha another embodiment, n or p is 0. ha another embodiment, n or p is 1. ha another embodiment, x is 0. ha another embodiment, x is 1. hi another embodiment, Rj is -F. ha another embodiment, Rj is -CI. ha another embodiment, R, is -Br. ha another embodiment, R, is -I. ha another embodiment, R, is -(C,-C6)alkyl. ha another embodiment, R, is -CH3.
In another embodiment, R, is -NO2.
In another embodiment, R, is -CN. ha another embodiment, R, is -OH. ha another embodiment, Rx is -OCH3. ha another embodiment, Rj is -NH2. ha another embodiment, Rj is -C(halo)3.
In another embodiment, Rj is -CH(halo)2. ha another embodiment, Rj is -CH2(halo). ha another embodiment, n and p are 1 and R2 is -halo, -CN, -OH, -O(Cj- C6)alkyl, -NO2, or -NH2. ha another embodiment, n and p are 1 and R2 is -(Cj-C10)alkyl, -(C2- Cj0)alkenyl, -(C2-Cι0)alkynyl, -(C3-Cj0)cycloalkyl, -(C8-Cj4)bicycloalkyl, -(C8- Ci4)tricycloalkyl, -(C5-Cj0)cycloalkenyl,-(C8-Cj )bicycloalkenyl, -(C8-Cj4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rj groups. ha another embodiment, n and p are 1 and R2 is -phenyl, -naphthyl, -(Cj4)aryl, or -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
In another embodiment, x is 1 and A is -C(O)N(R4)-. ha another embodiment, x is 1, A is -C(O)N(R4)-, and R4 is -H. ha another embodiment, x is 1, A is -C(O)N(R4)-, and R4 is -CH3. ha another embodiment, x is 1 and A is -C(S)N(R4)-.
In another embodiment, x is 1, A is -C(S)N(R4)-, and R4 is -H. ha another embodiment, x is 1, A is -C(S)N(R4)~, and R4 is -CH3.
In another embodiment, Ar2 is a benzothiazolyl group. ha another embodiment, Ar2 is a benzoimidazolyl group. hi another embodiment, Ar2 is a benzooxazolyl group.
In another embodiment, R8 and Rg are each independently -H, halo, -(C,- C6)alkyl, -O(Cj-C6)alkyl, -C(halo)3, -CH(halo)2, or -CH2(halo).
In another embodiment, at least one of R8 or Rg is -H. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I;
R4 is -H; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -F. R4 is -H; Ar2 is a benzothiazolyl group and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, -Br, or -I;
Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -iodo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rx is -F, -CI, Br, or -I;
Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arl is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R, is -F, -CI, Br, or -I;
Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and R, is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, A^ is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. La another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rt is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I;
Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, AJj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; R4 is -H; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F. R4 is -H; Ar2 is a benzothiazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or
-I; Ar2 is a benzothiazolyl group; R8 is -H; and R§ is -chloro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, AJ-J is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ajj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arl is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or
-I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rλ is -F; Ar2 is a benzothiazolyl group; R8 is -CF3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rx is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and g is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A j is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arx is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; j is -CH3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; j is -CF3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, -Br, or -I; R4 is -H; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -F. R4 is -H; Ar2 is a benzoimidazolyl group and R8 and R, are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI -Br, or -I;
Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I;
Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, A-Cj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, AJ-J is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I;
Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; and Rg and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzoimidazolyl group; Rg is -OCH2CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ^ , In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I;
Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; R, is -F; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group, n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; R4 is -H; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F. R4 is -H; Ar2 is a benzoimidazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI -Br, or
-I; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -fluoro. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. hi another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; Rg is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; Rg is -chloro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F; Ar2 is a benzoimidazolyl group; Rg is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; Rg is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arl is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, Br, or
-I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, A -J is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; Rx is -CH3; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Aij is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and g is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; Rg is -OCH2CH3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; Rg is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -F, -CI, -Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; R4 is -H; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F. R4 is -H; Ar2 is a benzooxazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; j is -F, -CI -Br, or -I;
Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; Rg is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; Rg is -iodo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; Rg is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; Rg is -iodo; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, Br, or -I;
Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -H; and R§ is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; Rg is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arl is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; Rg is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; Rg is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F, -CI, Br, or -I;
Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, ATj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and g is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; Rg is -chloro; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyridyl group, n is 0; Rt is -CH3; Ar2 is a benzooxazolyl group; R8 is -bromo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rt is -CH3; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and g is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; Rg is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; Rg is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rx is -CH3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, A^ is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; j is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; j is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; Rg is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group, n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F, -CI, -Br, or -I;
Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, Ar, is a pyridyl group, n is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar , is a pyridyl group, n is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and R§ is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group, n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; R4 is -H; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F. R4 is -H; Ar2 is a benzooxazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F, -CI -Br, or
-I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar t is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; Rg is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -chloro; and R, is -H. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar t is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; Rg is -chloro; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; Rg is -bromo; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro; and R, is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rx is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arl is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or
-I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Art is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -bromo. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; Rg is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; Rg is -iodo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Art is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; j is -CF3; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; Rg is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar j is a pyrimidinyl group, p is 0; Rj is -F, -CI, -Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; Rg is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimidinyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimidinyl, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rx is -F, -CI, -Br, or - I; R4 is -H; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F. R4 is -H; Ar2 is a benzothiazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or -
I; Ar2 is a benzothiazolyl group; R8 is -H; and R§ is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or -
I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arx is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, A^ is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; Rg is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or -
I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzothiazolyl group; Rg is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CF3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or -
I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Axx is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; j is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -bromo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -iodo. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or -
I; Ar2 is a benzothiazolyl group; Rg is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; Rg is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rt is -CH3; Ar2 is a benzothiazolyl group; Rg is -H; and R§ is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; R4 is -H; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F. R4 is - H; Ar2 is a benzothiazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI -
Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI - Br, or -I; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Aij is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -fluoro; and R§ is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI,
Br, or -I; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -bromo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rt is -CH3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CH3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -CH3; Ar2 is a benzothiazolyl group; Rg is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; Rg is -CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; Rg is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -chloro. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and R, is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzothiazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arx is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzothiazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; R, is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Art is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzothiazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; R4 is -H; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F. R4 is -H; Ar2 is a benzoimidazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or -
I; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -chloro., ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group and n is 0; R, is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, Ar , is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or -
I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration, ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; Rg is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; Rg is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyridyl group and n is 0; Rt is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or -
I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; R, is -F; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; Rg is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Art is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - 1; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -CH3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; R4 is -H; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, AJ-J is a pyriminidyl group and p is 0; Rj is -F. R4 is - H; Ar2 is a benzoimidazolyl group and Rg and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimimdyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyrimimdyl group and p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rt is -CI; Ar2 is a benzoimidazolyl group; Rg is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; Rg is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; Rg is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI,
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -H; and R, is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; Rg is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and R, is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -halo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -iodo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rt is -CF3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzoimidazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyrimimdyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI, -
Br, or -I; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -H; and Rg is -tert-butyl. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzoimidazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; R, is -F, -CI, -Br, or - I; R4 is -H; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; Rj is -F. R4 is -H; Ar2 is a benzooxazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI -Br, or -
I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; R, is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -chloro; and R§ is -H. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; R, is -F, -CI, -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Ar j is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -iodo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ar, is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or -
I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, Br, or - I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and R§ is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. h another embodiment, Ar, is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -chloro; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CF3;'and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Ar, is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -CH3; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F, -CI, -Br, or - 1; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyridyl group and n is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F, -CI, - Br, or -I; R4 is -H; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -F. R4 is - H; Ar2 is a benzooxazolyl group and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyrimimdyl group and p is 0; R, is -F, -CI - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -F, -CI -
Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar t is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; Rg is -H; and Rg is -iodo. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, h another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CI; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; Rg is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, a another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F, -CI, -
Br, or -I; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and R, is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; R, is -F, -CI,
Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arl is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; R, is -F, -CI, Br, or -I; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -F; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -bromo; and Rg is -H. h another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. a another embodiment, Arj is a pyriminidyl group and p is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ar, is a pyriminidyl group and p is 0; R, is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CF3; and Rg is -H. hi another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; and R8 and Rg are -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and g is -halo, ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -chloro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -bromo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -fluoro. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyrimhaidyl group and p is 0; R, is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -iodo. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -halo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -chloro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arj is a pyrimimdyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -bromo; and R, is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -fluoro; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, hi another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -iodo; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration.
In another embodiment, Ar, is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -CF3. a another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; Rg is -CF3; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -OCH2CH3. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CF3; Ar2 is a benzooxazolyl group; R8 is -OCH2CH3; and Rg is -H. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar j is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. i another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. hi another embodiment, Arx is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyriminidyl group and p is 0; Rj is -F, -CI, - Br, or -I; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. In another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -F; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration. In another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Arj is a pyriminidyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -tert-butyl; and Rg is -H. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, ATj is a pyrimimdyl group and p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -H; and Rg is -tert-butyl. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. In another embodiment, Arj is a pyriminidyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha another embodiment, Ar, is a pyriminidyl group, p is 0; Rj is -CH3; Ar2 is a benzooxazolyl group; R8 is -CH3; and Rg is -CH3. ha another embodiment, the carbon atom to which the R3 group is attached has the R configuration, ha another embodiment, the carbon atom to which the R3 group is attached has the S configuration. ha the Benzoazolylpiperazine Compounds the R3 group can be on any carbon of the piperazine ring, ha one embodiment, the R3 group is attached to a carbon atom adjacent to the nitrogen atom attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group, ha another embodiment, the R3 group is attached to a carbon atom adjacent to the nitrogen atom attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0. ha one embodiment, wherein the Benzoazolylpiperazine Compound has an R3 group, the carbon atom to which the R3 group is attached has the (R) configuration, ha another embodiment, wherein the Benzoazolylpiperazine Compound has an R3 group, the carbon atom to which the R3 group is attached has the (S) configuration. ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen atom attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; and the carbon to which the R3 group is attached is in the (R) configuration, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -(Cj-C4)alkyl unsubstituted or substituted with one or more halo groups, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -CH3. hi another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -CF3. ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -CH2CH3.
In another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen atom attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group when x is 0; and the carbon to which the R3 group is attached is in the (R) configuration, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nitrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -(Cι-C4)alkyl unsubstituted or substituted with one or more halo groups, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1 ; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -CH3. ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -CF3. In another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1 ; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and R3 is -CH2CH3.
In another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen atom attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; and the carbon to which the R3 group is attached is in the (S) configuration, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -(Cj-C4)alkyl unsubstituted or substituted with one or more halo groups, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -CH3. ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -CF3. In another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the pyridyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl group, or thiazanyl group; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -CH2CH3.
In another embodiment, the Benzoazolylpiperazine Compound has an R3 groups; the R3 group is attached to a carbon atom adjacent to a nifrogen atom attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; and the carbon to which the R3 group is attached is in the (S) configuration, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -(C,-C4)alkyl unsubstituted or substituted with one or more halo groups, ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the -(A)- group, when x is 1 ; or the R3 group is attached to the carbon atom adjacent to the nitrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -CH3. ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -CF3. ha another embodiment, the Benzoazolylpiperazine Compound has an R3 group; the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nitrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (S) configuration; and R3 is -CH2CH3. ha a preferred embodiment, the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; and the R3 group is a -CH3. ha another preferred embodiment, the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nitrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0 and the R3 group is a -CF3. ha another preferred embodiment, the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nitrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; and the R3 group is a -CH2CH3. ha another preferred embodiment, the R3 group is attached to a carbon atom adjacent to a nifrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nitrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; and the carbon to which the R3 group is attached is in the (R) configuration, ha another preferred embodiment, the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1 ; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and the R3 group is a -CH3. ha another prefened embodiment, the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and the R3 group is a -CF3. ha another preferred embodiment, the R3 group is attached to a carbon atom adjacent to a nitrogen attached to the -(A)- group, when x is 1; or the R3 group is attached to the carbon atom adjacent to the nifrogen atom attached to the benzothiazolyl group, the benzoimidazolyl group, or the benzooxazolyl group, when x is 0; the carbon to which the R3 group is attached is in the (R) configuration; and the R3 group is a -CH2CH3.
Illustrative Benzoazolylpiperazine Compounds are listed below in Tables I- xπ:
Table I
Figure imgf000368_0001
Figure imgf000368_0002
Figure imgf000369_0001
Figure imgf000370_0001
Figure imgf000371_0001
Figure imgf000372_0001
Figure imgf000373_0001
Figure imgf000374_0001
Figure imgf000375_0001
Figure imgf000376_0001
Figure imgf000377_0001
Figure imgf000378_0001
ALU -5-(4-methylthiazanyl) -H -tert-butyl
ALN -5-(4-methylthiazanyl) -H -iso-pxopyl
Table II
Figure imgf000380_0001
and pharmaceutically acceptable salts thereof, wherein:
Figure imgf000380_0002
Figure imgf000381_0001
Figure imgf000382_0001
Figure imgf000383_0001
Figure imgf000384_0001
Figure imgf000385_0001
Figure imgf000386_0001
Figure imgf000387_0001
Figure imgf000388_0001
Figure imgf000389_0001
Figure imgf000390_0001
Figure imgf000391_0001
Table III
Figure imgf000392_0001
and pharmaceutically acceptable salts thereof, wherein:
Figure imgf000392_0002
Figure imgf000393_0001
Figure imgf000394_0001
Figure imgf000395_0001
Figure imgf000396_0001
Figure imgf000397_0001
Figure imgf000398_0001
Figure imgf000399_0001
Figure imgf000400_0001
Figure imgf000401_0001
Figure imgf000402_0001
Figure imgf000403_0001
"a" means the Benzoazolylpiperazine Compound is racemic. "b" means the carbon atom of the piperazine ring attached to the methyl group in the R configuration.
"c" means the carbon atom of the piperazine ring attached to the methyl group in the S configuration.
Table IV
Figure imgf000404_0001
and harmaceuticall accetable salts thereof, wherein
Figure imgf000404_0002
Figure imgf000405_0001
Figure imgf000406_0001
Figure imgf000407_0001
Figure imgf000408_0001
Figure imgf000409_0001
Figure imgf000410_0001
Figure imgf000411_0001
Figure imgf000412_0001
Figure imgf000413_0001
Figure imgf000414_0001
"a" means the Benzoazolylpiperazine Compound is racemic. "b" means the carbon atom of the piperazine ring attached to the methyl group iguration.
"c" means the carbon atom of the piperazine ring attached to the methyl group iguration.
Table V
Figure imgf000416_0001
and pharmaceutically acceptable salts thereof, wherein:
Compound ATj R, E9
BNK -2-pyridazinyl -CI -H
BNL -2-pyridazinyl -Br -H
BNM -2-pyridazinyl -H
BNΝ -2-pyridazinyl -CH, -H
BNO -2-pyridazinyl -CF, -H
BNP -2-pyridazinyl -OCH, -H
BNQ -2-pyridazinyl -OCH H, -H
BNR -2-pyridazinyl -OCF, -H
BNS -2-pyridazinyl -tert-butyl -H
BNT -2-pyridazinyl -wo-propyl -H
BNU -2-pyridazinyl -C -CH,
BW -2-pyridazinyl -H -H
BNW -2-pyridazinyl -H -CI
BNX -2-pyridazinyl -H -Br
BNY -2-pyridazinyl -H -F
BNZ -2-pyridazinyl -H -CH,
BWA -2-pyridazinyl -H -CF,
Figure imgf000417_0001
Figure imgf000418_0001
Figure imgf000419_0001
Figure imgf000420_0001
Table VI
Figure imgf000421_0001
and harmaceuticall acce table salts thereof wherein:
Figure imgf000421_0002
Figure imgf000422_0001
Figure imgf000423_0001
Figure imgf000424_0001
Figure imgf000425_0001
Figure imgf000426_0001
Figure imgf000427_0001
Figure imgf000428_0001
Figure imgf000429_0001
Figure imgf000430_0001
Figure imgf000431_0001
Figure imgf000432_0001
Table VII
Figure imgf000433_0001
and harmaceuticall acce table salts thereof wherein:
Figure imgf000433_0002
Figure imgf000434_0001
Figure imgf000435_0001
Figure imgf000436_0001
Figure imgf000437_0001
"a" means the Benzoazolylpiperazine Compound is racemic. "b" means the carbon atom of the piperazine ring attached to the methyl group guration.
"c" means the carbon atom of the piperazine ring attached to the methyl group guration.
Table VIII
Figure imgf000439_0001
and harmaceuticall accetable salts thereof wherein:
Figure imgf000439_0002
Figure imgf000440_0001
Figure imgf000441_0001
Figure imgf000442_0001
Figure imgf000443_0001
Figure imgf000444_0001
Figure imgf000445_0001
Figure imgf000446_0001
Figure imgf000448_0001
Figure imgf000449_0001
"a" means the Benzoazolylpiperazine Compound is racemic. "b" means the carbon atom of the piperazine ring attached to the methyl group guration.
"c" means the carbon atom of the piperazine ring attached to the methyl group guration.
Table IX
Figure imgf000451_0001
and pharmaceutically acceptable salts thereof, wherein
Compound Arj - Raa E9
DDG -2-pyridazinyl -CI -H
DDH -2-pyridazinyl -Br -H
DDI -2-pyridazinyl -H
DDJ -2-pyridazinyl -CR -H
DDK -2-pyridazinyl -CF, -H
DDL -2-pyridazinyl -OCR -H
DDM -2-pyridazinyl -OCRCR -H
DDN -2-pyridazinyl -OCF, -H
DDO -2-pyridazinyl -tert-butyl -H
DDP -2-pyridazinyl -z'-fo-propyl -H
DDQ -2-pyridazinyl -CR -CR
DDR -2-pyridazinyl -H -H
DDS -2-pyridazinyl -H -CI
DDT -2-pyridazinyl -H -Br
DDU -2-pyridazinyl -H
DDV -2-pyridazinyl -H -CR
DDW -2-pyridazinyl -H -CF,
Figure imgf000452_0001
Figure imgf000453_0001
Figure imgf000454_0001
Figure imgf000455_0001
Table X
Figure imgf000456_0001
Figure imgf000456_0002
Figure imgf000457_0001
Figure imgf000458_0001
Figure imgf000459_0001
Figure imgf000460_0001
Figure imgf000461_0001
Figure imgf000462_0001
Figure imgf000463_0001
Figure imgf000464_0001
Figure imgf000465_0001
Figure imgf000466_0001
Figure imgf000467_0001
Table XI
Figure imgf000468_0001
Figure imgf000468_0002
Figure imgf000469_0001
Figure imgf000470_0001
Figure imgf000471_0001
Figure imgf000472_0001
"a" means the Benzoazolylpiperazine Compound is racemic. "b" means the carbon atom of the piperazine ring attached to the methyl group guration.
"c" means the carbon atom of the piperazine ring attached to the methyl group guration.
Table XII
Figure imgf000474_0001
Figure imgf000474_0002
Figure imgf000475_0001
Figure imgf000476_0001
Figure imgf000477_0001
Figure imgf000478_0001
Figure imgf000479_0001
Figure imgf000480_0001
Figure imgf000481_0001
Figure imgf000482_0001
Figure imgf000483_0001
Figure imgf000484_0001
Figure imgf000485_0001
"a" means the Benzoazolylpiperazine Compound is racemic.
"b" means the carbon atom of the piperazine ring attached to the methyl group in the R configuration. "c" means the carbon atom of the piperazine ring attached to the methyl group in the S configuration.
Table XIII
Figure imgf000486_0001
Figure imgf000486_0002
Figure imgf000487_0001
Figure imgf000488_0001
Figure imgf000489_0001
Figure imgf000490_0001
Figure imgf000491_0001
Figure imgf000492_0001
Figure imgf000493_0001
Figure imgf000494_0001
Figure imgf000495_0001
Figure imgf000496_0001
Figure imgf000497_0001
Table XIV
Figure imgf000498_0001
and harmaceuticall acce table salts thereof, wherein:
Figure imgf000498_0002
Figure imgf000499_0001
Figure imgf000500_0001
Figure imgf000501_0001
Figure imgf000502_0001
Figure imgf000503_0001
Figure imgf000504_0001
Figure imgf000505_0001
Figure imgf000506_0001
Figure imgf000507_0001
Figure imgf000508_0001
Figure imgf000509_0001
Table XV
Figure imgf000510_0001
and harnaaceuticall acce table salts thereof, wherein:
Figure imgf000510_0002
Figure imgf000511_0001
Figure imgf000512_0001
Figure imgf000513_0001
Figure imgf000514_0001
Figure imgf000515_0001
Figure imgf000516_0001
Figure imgf000517_0001
Figure imgf000518_0001
Figure imgf000519_0001
Figure imgf000520_0001
Figure imgf000521_0001
"a" means the Benzoazolylpiperazine Compound is racemic.
"b" means the carbon atom of the piperazine ring attached to the methyl group in the R configuration. "c" means the carbon atom of the piperazine ring attached to the methyl group in the S configuration.
Table XVI
Figure imgf000522_0001
Figure imgf000522_0002
Figure imgf000523_0001
Figure imgf000524_0001
Figure imgf000525_0001
Figure imgf000526_0001
Figure imgf000527_0001
Figure imgf000528_0001
Figure imgf000529_0001
Figure imgf000530_0001
Figure imgf000531_0001
Figure imgf000532_0001
"a" means the Benzoazolylpiperazine Compound is racemic. "b" means the carbon atom of the piperazine ring attached to the methyl group guration.
"c" means the carbon atom of the piperazine ring attached to the methyl group guration.
Table XIX
Figure imgf000534_0001
Figure imgf000534_0002
Figure imgf000535_0001
Figure imgf000536_0001
Table XX
Figure imgf000537_0001
Figure imgf000537_0002
Figure imgf000538_0001
Figure imgf000539_0001
Figure imgf000540_0001
and pharmaceutically acceptable salts thereof, wherein:
Figure imgf000540_0002
Figure imgf000541_0001
Figure imgf000542_0001
Figure imgf000543_0001
Figure imgf000543_0002
Figure imgf000544_0001
Figure imgf000545_0001
4.1 DEFINITIONS
As used herein, the terms used above having following meaning: "-(Cr0)alkyl" means a straight chain or branched non-cyclic hydrocarbon having from 1 to 10 carbon atoms. Representative straight chain -(CrC10)alkyls include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, -n-hexyl, -n-heptyl, -n-octyl, -n-nonyl, and -n- decyl. Representative branched -(CrC10)alkyls include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1,2-dimethylpentyl, 1,3- dimethylpentyl, 1,2-dimethylhexyl, 1,3-dimethylhexyl, 3,3-dimethylhexyl, 1,2- dimethylheptyl, 1,3-dimethylheptyl, and 3,3-dimethylheptyl.
Figure imgf000546_0001
means a straight chain or branched non-cyclic hydrocarbon having from 1 to 6 carbon atoms. Representative straight chain -(C,-C6)alkyls include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, and -n-hexyl. Representative branched -(Cr C6)alkyls include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, -neopentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1,1-dimethtylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylbutyl.
"-(Cj-C alkyi" means a straight chain or branched non-cyclic hydrocarbon having from 1 to 4 carbon atoms. Representative straight chain -(C^C^alkyls include -methyl, -ethyl, -n-propyl, and -n-butyl. Representative branched -(Cj-C alkyls include -isopropyl, -sec-butyl, -isobutyl, and -tert-butyl.
"-(C2-C10)alkenyl" means a straight chain or branched non-cyclic hydrocarbon having from 2 to 10 carbon atoms and including at least one carbon-carbon double bond. Representative straight chain and branched (C2-C10)alkenyls include -vinyl, -allyl, -1-butenyl, -2-butenyl, -isobutylenyl, -1-pentenyl, -2-pentenyl, -3 -methyl- 1-butenyl, -2-methyl-2-butenyl, -2,3-dimethyl-2-butenyl, -1-hexenyl, -2-hexenyl, -3-hexenyl, -1-heptenyl, -2-heptenyl, -3- heptenyl, -1-octenyl, -2-octenyl, -3-octenyl, -1-nonenyl, -2-nonenyl, -3-nonenyl, -1-decenyl, -2-decenyl, -3-decenyl and the like.
"-(C2-C6)alkenyι" means a straight chain or branched non-cyclic hydrocarbon having from 2 to 6 carbon atoms and including at least one carbon-carbon double bond. Representative straight chain and branched (C2-C6)alkenyls include -vinyl, -allyl, -1-butenyl, 5 -2-butenyl, -isobutylenyl, -1-pentenyl, -2-pentenyl, -3 -methyl- 1-butenyl, -2-methyl-2-butenyl, -2,3-dimethyl-2-butenyl, -1-hexenyl, 2-hexenyl, 3-hexenyl and the like.
"-(C2-C1o)alkynyl" means a straight chain or branched non-cyclic hydrocarbon having from 2 to 10 carbon atoms and including at least one carbon-carbon triple bond. Representative straight chain and branched -(C2-C10)alkynyls include -acetylenyl, -propynyl, 10 -1-butynyl, -2-butynyl, -1-pentynyl, -2-pentynyl, -3 -methyl- 1-butynyl, -4-pentynyl, -1- hexynyl, -2-hexynyl, -5-hexynyl, -1-heptynyl, -2-heptynyl, -6-heptynyl, -1-octynyl, -2-octynyl, -7-octynyl, -1-nonynyl, -2-nonynyl, -8-nonynyl, -1-decynyl, -2-decynyl, -9-decynyl and the like.
"-(C2-C6)alkynyl" means a straight chain or branched non-cyclic hydrocarbon 15 having from 2 to 6 carbon atoms and including at least one carbon-carbon triple bond. Representative straight chain and branched (C2-C6)alkynyls include -acetylenyl, -propynyl, -1-butynyl, -2-butynyl, -1-pentynyl, -2-pentynyl, -3-methyl- 1-butynyl, -4-pentynyl, -1-hexynyl, -2-hexynyl, -5-hexynyl and the like.
"-(C3-C10)cycloalkyl" means a saturated cyclic hydrocarbon having from 3 to 20 10 carbon atoms. Representative (C3-C10)cycloalkyls are -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, -cyclooctyl, -cyclononyl, and -cyclodecyl.
"-(C3-C8)cycloalkyl" means a saturated cyclic hydrocarbon having from 3 to 8 carbon atoms. Representative (C3-C8)cycloalkyls include -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, and -cyclooctyl. 25 "-(C8-C14)bicycloalkyl" means a bi-cyclic hydrocarbon ring system having from 8 to 14 carbon atoms and at least one saturated cyclic alkyl ring. Representative -(C8- C14)bicycloalkyls include -indanyl, -1,2,3,4-tetrahydronaphthyl, -5,6,7,8-tetrahydronaphthyl, -perhydronaphthyl and the like.
Figure imgf000547_0001
means a tri-cyclic hydrocarbon ring system having 30 from 8 to 14 carbon atoms and at least one saturated ring. Representative -(C8-
C14)ιricycloalkyls include -pyrenyl, -1,2,3,4-tetrahydroanthracenyl, -perhydroanthracenyl -aceanthreneyl, -1,2,3,4-tetrahydropenanthrenyl, -5,6,7,8-tetrahydrophenanthrenyl, -perhydrophenanthrenyl and the like.
"-(C5-C10)cycloaιkenyl" means a cyclic non-aromatic hydrocarbon having at least one carbon-carbon double bond in the cyclic system and from 5 to 10 carbon atoms. Representative (C5-C10)cycloalkenyls include -cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl,-cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, -cyclooctatetraenyl, -cyclononenyl -cyclononadienyl, -cyclodecenyl, -cyclodecadienyl and the like.
"-(C5-C8)cycloalkenyl" means a cyclic non-aromatic hydrocarbon having at least one carbon-carbon double bond in the cyclic system and from 5 to 8 carbon atoms. Representative (C5-C8)cycloalkenyls include -cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl, -cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, -cyclooctatetraenyl and the like.
"-(C8-C14)bicycloaιkenyι" means a bi-cyclic hydrocarbon ring system having at least one carbon-carbon double bond in each ring and from 8 to 14 carbon atoms. Representative -(C8-C14)bicycloalkenyls include -indenyl, -pentalenyl, -naphthalenyl, -azulenyl, -heptalenyl, -1,2,7,8-tetrahydronaphthalenyl and the like.
"-(C8-C14)tricycloalkenyl" means a tri-cyclic hydrocarbon ring system having at least one carbon-carbon double bond in each ring and from 8 to 14 carbon atoms. Representative -(C8-C14)tricycloalkenyls include -anthracenyl, -phenanthrenyl, -phenalenyl, -acenaphthalenyl, -w-indacenyl, s-indacenyl and the like.
"-(3- to 7-membered)heterocycle" or "-(3- to 7-membered)heterocyclo" means a 3- to 7-membered monocyclic heterocyclic ring which is either saturated, unsaturated non- aromatic, or aromatic. A 3-membered -heterocycle can contain up to 3 heteroatoms, and a 4- to 7-memberedheterocycle can contain up to 4 heteroatoms. Each heteroatom is independently selected from nitrogen, which can be quaternized; oxygen; and sulfur, including sulfoxide and sulfone. The -(3- to 7-membered)heterocycle can be attached via a nitrogen or carbon atom. Representative -(3- to 7-membered)heterocycles include pyridyl, furyl, thiophenyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, thiadiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, morpholinyl, pynolidinonyl, pynolidinyl, piperidinyl, piperazinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tefrahydrofuranyl, tetrahydropyranyl, tetrahydropyrindinyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, texrahydrothiopyranyl and the like.
"-(3- to 5-membered)heterocycle" or "-(3- to 5-membered)heterocyclo" means a 3- to 5-membered monocyclic heterocyclic ring which is either saturated, unsaturated non- aromatic, or aromatic. A 3-membered heterocycle can contain up to 3 heteroatoms, and a 4- to 5-membered heterocycle can contain up to 4 heteroatoms. Each heteroatom is independently selected from nitrogen, which can be quatemized; oxygen; and sulfur, including sulfoxide and sulfone. The -(3- to 5-membered)heterocycle can be attached via a nitrogen or carbon atom. Representative -(3- to 5-membered)heterocycles include furyl, thiophenyl, pyrrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, triazinyl, pynolidinonyl, pynolidinyl, hydantoinyl, oxiranyl, oxetanyl, tefrahydrofuranyl, tetrahydiOthiophenyl and the like.
"-(7- to 10-membered)bicycloheterocycle" or "-(7- to 10- membered)bicycloheterocyclo" means a 7- to 10-membered bicyclic, heterocyclic ring which is either saturated, unsaturated non-aromatic, or aromatic. A -(7- to 10- membered)bicycloheterocycle contains from 1 to 4 heteroatoms independently selected from nitrogen, which can be quatemized; oxygen; and sulfur, including sulfoxide and sulfone. The -(7- to 10-membered)bicycloheterocycle can be attached via a nitrogen or carbon atom. Representative -(7- to 10-membered)bicycloheterocycles include -quinolinyl, -isoquinolinyl, -chromonyl, -coumarinyl, -indolyl, -indolizinyl, -benzo[b]furanyl, - benzo[b]thiophenyl, -indazolyl, -purinyl, -4H-quinolizinyl, -isoquinolyl, -quinolyl, - phthalazinyl, -naphthyridinyl, -carbazolyl, - ^carbolinyl and the like.
"-(C14)aryl" means a 14-membered aromatic carbocyclic moiety such as -anthryl or -phenanthryl. "-(5- to 10-membered)heteroaryl" means an aromatic heterocycle ring of 5 to
10 members, including both mono- and bicyclic ring systems, wherein at least one carbon atom of one or both of the rings is replaced with a heteroatom independently selected from nitrogen, oxygen, and sulfur. One or both of the -(5- to 10-membered)heteroaryrs rings contain at least one carbon atom. Representative -(5- to 10-membered)heteroaryls include pyridyl, furyl, benzofuranyl, thiophenyl, benzothiophenyl, quinolinyl, pyrrolyl, indolyl, oxazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiadiazolyl, triazinyl, cinnolinyl, phthalazinyl, and quinazolinyl.
"-CH2(halo)" means a methyl group wherein one of the hydrogens of the methyl group has been replaced with a halogen. Representative -CH2(halo) groups include - CH2F, -CH2C1, -CH2Br, and -CH2I.
"-CH(halo)2" means a methyl group wherein two of the hydrogens of the methyl group have been replaced with a halogen. Representative -CH(halo)2 groups include - CHF2, -CHC12, -CHBr2, CHBrCl, CHC1I, and -CHI2.
"-C(halo)3" means a methyl group wherein each of the hydrogens of the methyl group has been replaced with a halogen. Representative -C(halo)3 groups include - CF3, -CC13, -CBr3, and -CI3.
"-Halogen" or "-Halo" means -F, -CI, -Br, or -I.
The phrase "pyridyl group" means
Figure imgf000550_0001
wherein R R2, and n are defined above for the Benzoazolylpiperazine Compounds of formula (la, Ha, and JJIa).
The phrase "pyrazinyl group" means,
Figure imgf000550_0002
wherein R R2, and p are defined above for the Benzoazolylpiperazine Compounds of formula (lb, Ha, and nib).
The phrase "pyrimidinyl group" means
Figure imgf000551_0001
wherein R R2, and p are defined above for the Benzoazolylpiperazine Compounds of formula (la), (Ha), and (HJa).
The phrase "pyridazinyl group" means
Figure imgf000551_0002
wherein Rx R2, and p are defined above for the Benzoazolylpiperazine Compounds of formula (lb), (lib), and ( b). The phrase "thiazanyl group" means
Figure imgf000551_0003
wherein R, is defined above for the Benzoazolylpiperazine Compounds of formula (lb), (Hb), and (mb).
The phrase "2-(3 -chloropyridyl)" means
Figure imgf000551_0004
The phrase "2-(3 -methylpyridyl)" means
Figure imgf000551_0005
The phrase "2-(3-CF3-pyridyl)" means
Figure imgf000552_0001
The phrase "2-(3-CHF2-ρyridyl)" means
Figure imgf000552_0002
The phrase "2-(3-hydroxypyridyl)" means
Figure imgf000552_0003
The phrase "2-(3-nitropyridyl)" means
Figure imgf000552_0004
The phrase "2-(3-cyanopyridyl)" means
Figure imgf000552_0005
The phrase "2-(3-bromopyridyl)" means
Figure imgf000552_0006
The phrase "2-(3-iodopyridyl)" means
Figure imgf000553_0001
The phrase "4-(5-chloropyrimidinyl)" means
Figure imgf000553_0002
The phrase "4-(5-methylpyrimidinyl)" means
Figure imgf000553_0003
The phrase "4-(5-fluoropyrimidinyl)" means
Figure imgf000553_0004
The phrase "2-(3 -chloropyrazinyl)" means
Figure imgf000553_0005
The phrase "2-(3 -methylpyrazinyl)" means
Figure imgf000553_0006
The phrase "2-(3-fluoropyrazinyl)" means
Figure imgf000554_0001
The phrase "3 -(4-chloropyridazinyl)" means
Figure imgf000554_0002
The phrase "3 -(4-methylpyridazinyl)" means
Figure imgf000554_0003
The phrase "3-(4-fluoropyridazinyl)" means
Figure imgf000554_0004
The phrase "5-(4-chlorothiazanyl)" means
Figure imgf000554_0005
The phrase "5-(4-methylthiazanyl)" means
Figure imgf000554_0006
The phrase "2-pyrazinyl" means
Figure imgf000555_0001
The phrase "2-pyridazinyl" means
Figure imgf000555_0002
The phrase "4-thiazanyl" means
Figure imgf000555_0003
The phrase "5-(4-fluorothiazanyl)" means
Figure imgf000555_0004
The phrase "benzoimidiazolyl group " means
Figure imgf000555_0005
wherein Rg, Rg and R10 are defined above for the Benzoazolylpiperazine Compounds of formula (Ha) and (lib).
The phrase "benzothiazolyl group" means
Figure imgf000556_0001
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds of formula (la) and (lb).
The phrase "benzooxazolyl group" means
Figure imgf000556_0002
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds of formula (ma) and (mb).
The term "animal," includes, but is not limited to, a cow, monkey, baboon, chimpanzee, horse, sheep, pig, chicken, turkey, quail, cat, dog, mouse, rat, rabbit, guinea pig, and human.
The phrase "pharmaceutically acceptable salt," as used herein, includes a salt formed from an acid and a basic nitrogen group of one of the Benzoazolylpiperazine
Compounds. Illustrative salts include, but are not limited, to sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, /?-toluenesulfonate, and pamoate (i.e., l,r-methylene-bis-(2-hydroxy-3-naphthoate)) salts. The term "pharmaceutically acceptable salt" also includes a salt prepared from a Benzoazolylpiperazine Compound having an acidic functional group, such as a carboxylic acid functional group, and a pharmaceutically acceptable inorganic or organic base. Suitable bases include, but are not limited to, hydroxides of alkali metals such as sodium, potassium, and lithium; hydroxides of alkaline earth metal such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia and organic amines, such as unsubstituted or hydroxy-substituted mono-, di-, or trialkylamines; dicyclohexylamine; tributyl amine; pyridine; N-methyl,N-ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-hydroxy-lower alkyl amines), such as mono-, bis-, or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butylamine, or tris-(hydroxymethyl)methylamine, N,N,-di-lower alkyl-N-(hydroxy lower alkyl)-amines, such as N,N,-dimethyl-N-(2-hydroxyethyl)amine, or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; and amino acids such as arginine, lysine and the like.
The phrase "effective amount," when used in connection with a Benzoazolylpiperazine Compound means an amount effective for: (a) treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression; or (b) inhibiting VR1, mGluRl, or mGluR5 function in a cell.
The phrase "effective amount," when used in connection with the another therapeutic agent means an amount for providing the therapeutic effect of the therapeutic agent.
When a first group is "substituted with one or more" second groups, one or more hydrogen atoms of the first group is replaced with a corresponding number of second groups. When the number of second groups is two or greater, each second group can be the same or different, ha one embodiment, the number of second groups is one or two. ha another embodiment, the number of second groups is one.
The term "DMSO" means dimethyl sulfoxide. The term "DCM" means dichloromethane.
The term "UI" means urinary incontinence. The term "IBD" means inflammatory-bowel disease.
The term "IBS" means irritable-bowel syndrome.
The term "ALS" means amyotrophic lateral sclerosis.
The phrase "treatment of and "treating" includes the amelioration or cessation of pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression, or a symptom thereof. The phrase "prevention of and "preventing" includes the avoidance of the onset of pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression, or a symptom thereof.
4.2 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS
The Benzoazolylpiperazine Compounds can be made using conventional organic synthesis or by the following illustrative methods shown in the schemes below.
4.2.1 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA (IA". AND (IB) WHEREIN X IS 1 AND A IS -CFOVNR. The Benzoazolylpiperazine Compounds of formula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H, can be obtained by the following illustrative method shown in Scheme A:
Figure imgf000559_0001
Benzoazolylpiperazine Compounds of Formula (la) and (lb)
wherein Arl5 R3, R8, Rg and m are defined above for the Benzoazolylpiperazine Compounds of formula (la) and (lb).
Scheme A
A compound of formula B (about 2 mmol) is dissolved in an aprotic organic solvent (about 3 mL). To the resulting solution is added a compound of formula A (about 2 mmol) and the resulting reaction mixture allowed to stir for about 10 min. The solvent is then removed under reduced pressure to provide the Benzoazolylpiperazine Compound of formula (la) or (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H. The
Benzoazolylpiperazine Compounds of formula (la) and (lb) can be purified on a silica column eluted with 5:95 ethyl acetate / hexane.
The compound of formula B can be obtained as shown below in Scheme B:
Figure imgf000560_0001
B wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds of formula (la) and (lb).
Scheme B
A compound of formula D (about 0.75 eq.) in an aprotic organic solvent (about 0.04 M) is cooled to about 0°C. To the cooled solution is slowly added a solution of a compound of formula C (about 0.75 eq.) in an aprotic organic solvent (about 0.4 M). The resulting reaction mixture is stined at 0°C for about 5 min. and about 0.75 eq. of triethylamine are added to the reaction mixture. The reaction mixture is then allowed to warm to room temperature and the solvent is then removed under reduced pressure to provide the compound of formula B. The compound of formula D is commercially available from Sigma- Aldrich, St. Louis, MO (www.sigma-aldrich.com). Compounds of formula C are commercially available or can be prepared by the following illustrative method shown below in Scheme C.
Figure imgf000560_0002
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds of formula (la) and (lb).
Scheme C To a stirred solution of aniline U (about 74 mmol) and potassium thiocyanate (about 148 mmol) in about 100 mL of glacial acetic acid is added dropwise a solution of bromine (about 74 mmol) in about 25 mL of glacial acetic acid. The flask containing the bromine in acetic acid is then rinsed with about 15 mL of acetic acid which is combined with the solution of aniline U. The resulting reaction mixture is vigorously st red at room temperature for between about 2 h and about 24 h. The reaction mixture is then poured over crushed ice (about 500 mL) and the pH of the resulting mixture adjusted to a value of about 10 using ammonium hydroxide to provide a precipitate. The resulting precipitate is collected by filtration and recrystallized from toluene to provide the compound of formula C. Compounds of formula U are commercially available or can be prepared by methods well known to those skilled in the art.
The compound of formula A can be obtained as shown below in Scheme D:
Figure imgf000562_0001
Al
Figure imgf000562_0002
F2 H
A2
Figure imgf000562_0003
A3
Figure imgf000562_0004
A4
Figure imgf000563_0001
A5
wherein Rl5 R2, R3, m, n, and p are defined above for the Benzoazolylpiperazine Compounds offormula (la) and (lb) and X is a halogen. Scheme D
A compound offormula F1-F5 (about 20 mmol) is reacted with a compound offormula E (about 27.5 mmol) in about 15 mL of DMSO in the presence of triethylamine (about 30 mmol), optionally with heating, for about 24 h to provide a compound offormula A. The compound offormula A is isolated from the reaction mixture and purified, ha one embodiment, the compound of fonnula A is purified using column chromatography or recrystallization.
Compounds offormula E and F are commercially available or can be prepared by methods well known to those skilled in the art. The compound of formula E wherein m is 0 and the compound offormula E wherein m is 1 and R3 is (R) -CH3 or (S) -CH3 are commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-aldrich.com). ha one embodiment, X is bromide, chloride, or iodide.
The Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl can be obtained by the following illustrative method shown below in Scheme E.
Figure imgf000564_0001
Benzoazolylpiperazine Compounds of Formula (la) and (lb)
wherein Ax,, R3, R4, R8, Rg, and m are defined above for the Benzoazolylpiperazine Compounds offormula (la) and (lb) and X is a halogen.
Scheme E
To a solution of a Benzoazolylpiperazine compound offormula (la) or (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H (about 1 eq.), obtained as described above in Scheme A, in DMF at 0°C, is added a DMF solution of NaH (about 2 eq.). The resulting reaction mixture is allowed to warm to room temperature over about 1 h. To the resulting mixture is added about 1.2 eq. of an alkyl halide, R4X, and the resulting reaction mixture allowed to stir until the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl is formed. The progress of the reaction can be monitored using conventional analytical techniques including, but not limited to, high pressure liquid chromatography (HPLC), column chromatography, thin-layer chromatography (TLC), column chromatography, gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy such as lU and 13C NMR. The Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -( -C^alkyl is then isolated and purified. In one embodiment, the Benzoazolylpiperazine Compounds of formula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl is isolated by removing the solvent under reduced pressure. In another embodiment, the
Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -( -C^alkyl is isolated by extraction. The Benzoazolylpiperazine Compounds of formula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl can be purified, for example, by column chromatography or recrystallization.
4.2.2 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA
(IA AND OB) WHEREIN x IS 1 AND A is -CfSVNR.
The Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(S)-NR4-, and R4 is -H can be obtained by the following illustrative method in Scheme F:
Figure imgf000565_0001
Benzoazolylpiperazine Compounds of Formula (la) and (lb) wherein Arl5 R3, R8, Rg and m are defined above for the Benzoazolylpiperazine Compounds offormula (la) and (lb).
Scheme F
A Compound of Formula C (about 2 mmol), l,l'-thiocarbonyldiimidazole
(about 2 mmol) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma- aldrich.com)), and 4-dimethylaminopyridine (DMAP) (commercially available from Sigma- Aldrich, St. Louis, MO (www.sigma-aldrich.com)) are suspended in DMSO (about 3 mL) at room temperature and the resulting mixture is heated at about 100°C for about 6 h. The resulting reaction mixture is then cooled to room temperature and a compound of Formula A (about 2 mmol) is added to the reaction mixture and the reaction mixture is heated to about 100°C for about 16 h. The solvent is then removed under reduced pressure to provide the Benzoazolylpiperazine Compound offormula (la) or (lb) wherein x is 1, A is -C(S)-NR4-, and R4 is -H. The Benzoazolylpiperazine Compounds offormula (la) and (lb) can be purified on a silica column eluted with 5 :95 ethyl acetate / hexane.
The Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(S)-NR4-, and R4 is -(CrC6)alkyl can be obtained by a method analogous to the method used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl as described in Scheme E except that a Benzoazolylpiperazine Compound offormula (la) and (lb) wherein x is 1, A is -C(S)-NR4-, and R4 is -H, obtained as described above in Scheme F, is used in place of the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H.
4.2.3 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA
(IA) AND (IB WHEREIN X IS 0
The Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 0 can be obtained by the following illustrative method shown below in Scheme G:
Figure imgf000567_0001
Benzoazolylpiperazine Compounds of Formula (la) or (lb) wherein Arl5 R3, R8, Rg, and m are defined above for the Benzoazolylpiperazine Compounds offormula (la) and (lb).
Scheme G
A compound of Formula A (about 1 mmol) and a compound of Formula G (about 1 mmol) are dissolved in DMSO (about 3 mL) and heated at a temperature of between about 140°C and 150°C for about 12 h. The mixture is cooled to room temperature and the solvent removed under reduced pressure to provide a residue that is purified using silica gel flash chromatography (gradient elution from 2:98 methanohDCM to 6:94 methano DCM) to provide the Benzoazolylpiperazine Compound offormula (la) or (lb) wherein x is 0.
The compound of Formula A can be obtained as shown above in Scheme D. The compounds of Formula G are commercially available or can be prepared by procedures well known to those skilled in the art. An illustrative method for preparing compounds of Formula G is shown below in Scheme H.
Figure imgf000568_0001
AA
Rs-^/-^^ POCI3 Rfl^^ e xX >=o Xi -
AA BB wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (la) and (lb).
Scheme H A compound of Formula Z (about 5 to about 10 mmol) and carbodiimidazole (CDI) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma- aldrich.com)) (about 2 eq) is dissolved in THF (about 50 to about 70 mL) and the resulting reaction mixture is heated at reflux temperature for about 4 hours. The reaction mixture is then concentrated under reduced pressure to provide a residue. Ethyl acetate (about 50 mL) is added to the residue and the resulting insoluble material is collected by filtration and washed with ethyl acetate to provide a compound of Formula AA. The compound of Formula AA is then reacted with POCl3 according to the procedure described in J Med. Chem. 40:586-593
(1997) to provide the compound of Formula BB. The compounds of Formula Z are commercially available or can be prepared by procedures well known to those skilled in the art. An illustrative procedure for obtaining a compound of Formula Z is shown below in
Scheme I:
Figure imgf000568_0002
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (la) and (lb).
Scheme I Thiol CC (about 12 mmol) is dissolved in concentrated sulfuric acid (about 10 mL) at 0°C and the resulting solution cooled to a temperature of about -13°C to about -15°C. About 1 mL of 70% nitric acid is added to the resulting solution over a time period of about 30 min. and the resulting reaction mixture allowed to stir for about 2 h at a temperature of between about -13°C to about -15°C. The reaction mixture is then poured into ice water (about 100 mL), neutralized with 5% to 10% aqueous sodium hydroxide, and extracted with about 50 mL of chloroform. The chloroform layer is separated from the aqueous layer and removed under reduced pressure to provide a residue that is purified using flash chromatography (silica column and chloroform eluant) to provide a compound of Formula DD. The compound of Formula DD is dissolved in ethanol (about 50 mL) and hydrogenated for about 12 h at room temperature using 10% palladium on carbon as a catalyst. The catalyst is removed by filtration and the ethanol is removed under reduced pressure to provide a residue that is purified using flash chromatography (silica gel eluted with 20:1 dichloromethane:methanol) to provide the compound of Formula EE. The compounds of Formula CC are commercially available or can be prepared by procedures well known to those skilled in the art.
4.2.4 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA (IIA) AND (IIB) WHEREIN X IS 0 The Benzoazolylpiperazine Compounds of formula (Ila) wherein R10 is -H and formula (lib) wherein x is 0 and R10 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 0 as described above in section 4.2.3, Scheme G except that a compound of Formula H, shown below,
Figure imgf000569_0001
H wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (Ha) and (lib), is used in place of the compound of Formula G as illustrated below in Scheme J:
Figure imgf000570_0001
Benzoazolylpiperazine Compounds of Formula (Ha) or (lib)
wherein Arl5 R3, R8, Rg, and m are defined above for the Benzoazolylpiperazine Compounds offormula (Ha) and (lib).
Scheme J
A compound of Formula A (about 1 mmol) and a compound of Formula H (about 1 mmol) are dissolved in toluene or p-xylene in a sealed tube and heated at a temperature of between about 140°C and 150°C for about 3 days. The mixture is cooled to room temperature and the solvent removed under reduced pressure to provide a residue that is purified using flash chromatography (silica gel with a gradient elution from 2% methanol: dichloromethane to 6% methanohdichloromethane) to provide the Benzoazolylpiperazine Compound offormula (Ha) and formula (lib) wherein x is 0. The compound of Formula A can be obtained as shown above in Scheme D.
The compounds of Formula H are commercially available or can be prepared by procedures well known to those skilled in the art. An illustrative method for preparing the compound of Formula H is shown below in Scheme K:
Figure imgf000571_0001
P rOuCulι33
Figure imgf000571_0002
Figure imgf000571_0003
J H
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (Ha) and (lib).
Scheme K
A compound of Formula I (about 5 to about 10 mmol) and carbodiimidazole (CDI) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma- aldrich.com)) (about 2 eq) is dissolved in THF (about 50 to about 70 mL) and the resulting reaction mixture is heated at reflux temperature for about 4 hours. The reaction mixture is then concentrated under reduced pressure to provide a residue. Ethyl acetate (about 50 mL) is added to the residue and the resulting insoluble material is collected by filtration and washed with ethyl acetate to provide a compound of Formula J. The compound of Formula J is then reacted with POCl3 according to the procedure described in J. Med. Chem. 40:586-593 (1997) to provide the compound of Formula H. The compounds of Formula I are commercially available or can be prepared by procedures well known to those skilled in the art. An illustrative procedure for obtaining a compound of Formula I is shown below in Scheme L:
Figure imgf000571_0004
V W T wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (Ha) and (Hb).
Scheme L
Aniline hydrochloride V (about 12 mmol) is dissolved in concentrated sulfuric acid (about 10 mL) at 0°C and the resulting solution cooled to a temperature of about -13°C to about -15°C. About 1 mL of 70% nitric acid is added to the resulting solution over a time period of about 30 min. and the resulting reaction mixture allowed to stir for about 2 h at a temperature of between about -13°C to about -15°C. The reaction mixture is then poured into ice water (about 100 mL), neutralized with 5% to 10% aqueous sodium hydroxide and extracted with about 50 mL of chloroform. The chloroform is separated from the aqueous layer and removed under reduced pressure to provide a residue that is purified using flash chromatography (silica column and chloroform eluant) to provide a compound of Formula W. The compound of Formula W is dissolved in ethanol (about 50 mL) and hydrogenated for about 12 h at room temperature using 10% palladium on carbon as a catalyst. The catalyst is removed by filtration and the ethanol is removed under reduced pressure to provide a residue that is purified using flash chromatography (silica gel eluted with 20: 1 dichloromethane:methanol) to provide the compound of Formula I. The compounds of Formula V are commercially available or can be prepared by procedures well known to those skilled in the art.
The Benzoazolylpiperazine Compounds offormula (11a) wherein R10 is -(Cr C4)alkyl and formula (lib) wherein x is 0 and R10 is -(CrC4)alkyl can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (Ha) and (lib) wherein x is 0 and R10 is -H, as described above in Scheme J, except that a compound of Formula K, shown below
Figure imgf000572_0001
K wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (Ha) and (Ob) and R10 is a -(CrC6)alkyl is used in place of the compound of Formula H. The compound of Formula K can be obtained as described below in Scheme M
Figure imgf000573_0001
H
K wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (Ha) and (lib), R10 is a -(C1-C6)alkyl, and X is a halogen.
Scheme M
NaH (about 2 eq) is added to a solution of a compound of Formula H in DMF at 0°C and the resulting mixture is allowed to stir and to warm to room temperature over a period of about one hour. An alkyl halide, R10-X. (about 1.2 eq) is then added to the solution and the resulting reaction mixture allowed to stir until the compound of Formula K is produced, ha one embodiment, the alkyl halide is an alkyl iodide. The formation of the compound of Formula K can be monitored by analytical methods well known to those skilled in the art including, but not limited to, liquid chromatography, column chromatography, gas chromatography, thin-layer chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy such as !H and 13C NMR. Water is then added to the reaction mixture to produce a precipitate of the compound of Formula K which is filtered, collected, and dried. The compound of Formula H can be obtained as described above in Scheme
K.
4.2.5 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA CLIB) WHEREIN X IS 1 AND A is -Cf/OVN , The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(O)-NR4-, R4 is -H, and R10 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H as described above in Scheme A except that a compound of Formula L, shown below,
Figure imgf000574_0001
L wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (lib), is used in place of the compound of Formula B.
The Compound of Formula L can be obtained by a method analogous to that used to obtain the compound of Formula B as described in section 4.2.1, Scheme B, except that a compound of Formula M, shown below,
Figure imgf000574_0002
M wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (lib), is used in place of the compound of Formula C. Compounds of Formula M are commercially available or can be prepared by procedures well known to those skilled in the art. An illustrative procedure for obtaining a compound of Formula M is shown below in Scheme N:
Figure imgf000575_0001
H M
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula
(nb)
Scheme N A compound of Formula H (about 1 mmol), prepared as described above in Scheme K, is dissolved in excess aqueous ammonia in a sealed tube and heated at a temperature of between about 140°C and 150°C for about 3 days. The mixture is cooled to room temperature and the solvent removed under reduced pressure to provide a residue, ha another embodiment, the mixture is cooled to room temperature, extracted with an organic solvent, the organic phase separated from the aqueous phase, and the organic solvent removed under reduced pressure to provide a residue. The residue is then purified to provide the compound of Formula M. ha one embodiment, the residue is purified by recrystallization. ha another embodiment, the residue is purified using flash chromatography.
The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(O)-NR4-, R4 is -H, and R10 is
Figure imgf000575_0002
can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(O)-NR4-, R4 is -H, and R10 is -H except that a compound of Formula N, shown below,
Figure imgf000575_0003
N wherein R8, Rg, and R10 are defined above for the Benzoazolylpiperazine Compounds of formula (lib), is used in place of the Compound of Formula L. The compound of Formula N can be obtained by a method analogous to that used to obtain the compound of Formula L except that a compound of Formula O, shown below,
Figure imgf000576_0001
O wherein R8, Rg, and R10 are defined above for the Benzoazolylpiperazine Compounds of formula (lib), is used in place of the compound of Formula M. The compound of Formula O can be obtained as shown below in Scheme N:
Figure imgf000576_0002
wherein R8, Rg, and R10 are defined above for the Benzoazolylpiperazine Compounds of formula (lib).
Scheme N NaH (about 2 eq) is added to a solution of a compound of Formula M in DMF at 0°C and the resulting mixture is allowed to stir and to warm to room temperature over a period of about one hour. An alkyl halide, R10-X, (about 1 eq.) is then added to the solution and the resulting reaction mixture allowed to stir until a mixture of acompound of Formula O and a compound of Formula X is produced, ha one embodiment, the alkyl halide is an alkyl iodide. The formation of the compound of Formula O and the compound of Formula X can be monitored by analytical methods well known to those skilled in the art including, but not limited to, those described above. Water is then added to the reaction mixture to produce a precipitate of the compound of Formula O and the compound of Formula X which are collected by filtration. The compound of Formula O and the compound of Formula X are then separated to provide the compound of Formula O. The compound of Formula O and the compound of Formula X can be separated by analytical methods well known to those skilled in the art including, but not limited to, column chromatography, preparative TLC, preparative HPLC, and preparative GC.
The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(O)-NR4-, R4 is -(C,-C6)alkyl, and R10 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl as shown above in Scheme E except that the
Benzoazolylpiperazine Compounds offormula (nb) wherein x is 1, A is -C(O)-NR4-, R4 is - H, and R10 is -H, prepared as described above, is used in place of the Benzoazolylpiperazine compound offormula (la) or (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H.
The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(O)-NR4-, R4 is -(CrC6)alkyl, and RJ0 is -(CrC4)alkyl can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl as shown above in Scheme E except that the Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(O)-NR4-, R4 is -H, and R10 is -( -C^alkyl, prepared as described above, is used in place of the Benzoazolylpiperazine compound offormula (la) or (lb) wherein x is 1, A is -C(O)- NR4-, and R4 is -H.
4.2.6 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA GIB) WHEREIN x IS 1 AND A IS -C(SVNRι- The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is
-C(S)-NR4-, R4 is -H, and R10 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1 and A is -C(S)-NR4-, and R4 is -H as described above in Scheme F except that a compound of Formula M is used in place of the compound of Formula C. The compound of Formula M can be obtained as described above.
The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(S)-NR4-, R4 is -H, and R10 is -(CrC4)alkyl can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(S)-NR4-, and R4 is -H, as described in section 4.2.2, Scheme F, except that a compound of Formula O is used in place of the compound of Formula C. The compound of Formula O can be obtained as described above.
The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(S)-NR4-, R4 is -(C1-C6)alkyl, and R10 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl as described above in Scheme E except that the Benzoylpiperazine Compound of Formula (Ha) wherein A is-C(S)-NR4-, R4 is -H, and Rι0 is -H, prepared as described above, is used in place of the Benzoazolylpiperazine Compounds of formula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H.
The Benzoazolylpiperazine Compounds offormula (lib) wherein x is 1, A is -C(S)-NR4-, R4 is -(CrC6)alkyl, and R10 is -(CrC4)alkyl can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(C,-C6)alkyl as described above in Scheme E except that the Benzoylpiperazine Compound of Formula (Ha) wherein A is-C(S)-NR4-, R4 is -H, and R10 is
Figure imgf000578_0001
prepared as described above, is used in place of the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H.
4.2.7 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA (IIIA) AND (IHB WHEREIN x IS 1 AND A is -C(OVNR.
The Benzoazolylpiperazine Compounds offormula (Ilia) and (mb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1 and A is -C(O)-NR4 as described in section 4.2.1, Scheme A, except that a compound of Formula P, shown below,
Figure imgf000579_0001
P wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula
(ma) and (mb), is used in place of the compound of Formula B.
The Compound of Formula P can be obtained by a method analogous to that used to obtain the compound of Formula B as described above in Scheme B except that a compound of Formula Q, shown below,
Figure imgf000579_0002
Q wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula
(ma) and (mb), is used in place of the compound of Formula C. The compounds of Formula Q are commercially available or can be prepared by procedures well known to those skilled in the art. The compounds of Formula Q can be obtained by a method analogous to that used to obtain the compound of Formula BB, as described in Scheme H, except that a compound of Formula HH, shown below,
Figure imgf000580_0001
HH is used in place of a compound of Formula Z.
An illustrative procedure for obtaining a compound of Formula HH is shown below in Scheme O:
Figure imgf000580_0002
FF GG HH
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (ma) and (mb).
Scheme O
Phenol FF (about 12 mmol) is dissolved in concentrated sulfuric acid (about 10 mL) at 0°C and the resulting solution cooled to a temperature of about -13°C to about -15°C. About 1 mL of 70% mtric acid is added to the resulting solution over a time period of about 30 min. and the resulting reaction mixture allowed to stir for about 2 h at a temperature of between about -13°C to about -15°C. The reaction mixture is then poured into ice water (about 100 mL), neutralized with 5% to 10% aqueous sodium hydroxide, and extracted with about 50 mL of chloroform. The chloroform is separated from the aqueous layer and removed under reduced pressure to provide a residue that is purified using flash chromatography (silica column and chloroform eluant) to provide a compound of Formula GG The compound of Formula GG is dissolved in ethanol (about 50 mL) and hydrogenated for about 12 h at room temperature using 10% palladium on carbon as a catalyst. The catalyst is removed by filtration and the ethanol is removed under reduced pressure to provide a residue that is purified using flash chromatography (silica gel eluted with 20:1 dichloromethane:methanol) to provide the compound of Formula HH The compounds of Formula FF are commercially available or can be prepared by procedures well known to those skilled in the art. The Benzoazolylpiperazine Compounds offormula ( a) and (IHb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl can be obtained by a method analogous to the method used to obtain the Benzoazolylpiperazine Compounds of formula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(CrC6)alkyl as shown above in Scheme E except that the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H is replaced with a Benzoazolylpiperazine Compounds offormula (ma) and (mb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H, obtained as described above.
4.2.8 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA (IIIA^ AND (I B) WHEREIN x IS 1 AND A is -C(SVNR.
The Benzoazolylpiperazine Compounds offormula (ma) and (mb) wherein x is 1, A is -C(S)-NR4-, and R4 is -H can be obtained by a method analogous to that used to obtain the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1 and A is -C(S)-NR4-, and R4 is -H as described above in Scheme F except that a compound of Formula Q is used in place of the compound of Formula C. The compound of Formula Q can be obtained as described above.
The Benzoazolylpiperazine Compounds offormula (ma) and (mb) wherein x is 1, A is -C(S)-NR4-, and R4 is -(CrC6)alkyl can be obtained by a method analogous to the method used to obtain the Benzoazolylpiperazine Compounds of formula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -(C,-C6)alkyl as described in Scheme E except that a Benzoazolylpiperazine Compound offormula (ma) and (IDb) wherein x is 1, A is -C(S)- NR4-, and R4 is -H, obtained as described above, is used in place of the Benzoazolylpiperazine Compounds offormula (la) and (lb) wherein x is 1, A is -C(O)-NR4-, and R4 is -H.
4.2.9 METHODS FOR MAKING THE BENZOAZOLYLPIPERAZINE COMPOUNDS OF FORMULA (IIIA) AND QI-ϋEfl WHEREIN x IS 0
The Benzoazolylpiperazine Compounds offormula (ma) and ( b) wherein x is 0 can be obtained by the following illustrative method shown in Scheme P.
Figure imgf000582_0001
Figure imgf000582_0002
Benzoazolylpiperazine Compounds of Formula (Hla) and (IHb) wherein Arl5 R3, R8, Rg, and m are above for the Benzoazolylpiperazine Compounds of formula (ma) and (mb)
Scheme P
A compound of Formula S (about 15 to about 20 mmol) and a compound of Formula T (about 1 eq.) are dissolved in ethanol (about 30 to about 40 mL) and the resulting reaction mixture heated at reflux temperature for about 5 h. The reaction mixture is concentrated under reduced pressure to provide a residue that is diluted with water (about 30 mL) and acidified with acetic acid to a pH value of about 6. The aqueous mixture is then extracted with ethyl acetate, the ethyl acetate dried
Figure imgf000582_0003
and the solvent removed under reduced pressure to provide a compound of Formula Y which is used without further purification. The compound of Formula Y (about 1 mmol) and a compound of Formula A (about 1 eq.) are dissolved in toluene or p-xylene (about 0.5. mL to about 1 mL) and the reaction mixture heated in a sealed tube at a temperature of about 150°C for about 24 h. The reaction mixture is concentrated under reduced pressure to provide a residue. The resulting residue can be purified using flash chromatography (silica gel, 5:95 methanohDCM) to provide the Benzoazolylpiperazine Compounds offormula ( a) and (IHb) wherein x is 0. The compounds of Formula S are commercially available or can be prepared by procedures well known to those skilled in the art. An illustrative procedure for obtaining a compound of Formula S is shown below in Scheme Q:
Figure imgf000583_0001
wherein R8 and Rg are defined above for the Benzoazolylpiperazine Compounds offormula (ma) and (mb). 10 Scheme Q
Phenol II (about 12 mmol) is dissolved in concentrated sulfuric acid (about 10 mL) at 0°C and the resulting solution cooled to a temperature of about -13°C to about -15°C. About 1 mL of 70% nitric acid is added to the resulting solution over a time period of about
15 30 min. and the resulting reaction mixture allowed to stir for about 2 h at a temperature of between about -13°C to about -15°C. The reaction mixture is then poured into ice water (about 100 mL), neutralized with 5% to 10% aqueous sodium hydroxide and extracted with about 50 mL of chloroform. The chloroform is separated from the aqueous layer and removed under reduced pressure to provide a residue that is purified using flash
20 chromatography (silica column and chloroform eluant) to provide a compound of Formula JJ. The compound of Formula JJ is dissolved in ethanol (about 50 mL) and hydrogenated for about 12 h at room temperature usingl0% palladium on carbon as a catalyst. The catalyst is removed by filtration and the ethanol is removed under reduced pressure to provide a residue that is purified using flash chromatography (silica gel eluted with 20: 1
25 dichloromethane:methanol) to provide the compound of Formula S. The compounds of Formula S are commercially available or can be prepared by procedures well known to those skilled in the art.
The compound of Formula T is commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-aldrich.com).
30 The compounds of Formula A can be obtained as described above. Suitable aprotic organic solvents for use in the illustrative methods include, but are not limited to, DCM, DMSO, chloroform, toluene, benzene, acetonitrile, carbon tetrachloride, pentane, hexane, ligroin, and diethylether. ha one embodiment, the aprotic organic solvent is DCM. Certain Benzoazolylpiperazine Compounds can have one or more asymmetric centers and therefore exist in different enantiomeric and diastereomeric forms. A Benzoazolylpiperazine Compound can be in the form of an optical isomer or a diastereomer. Accordingly, the invention encompasses Benzoazolylpiperazine Compounds and their uses as described herein in the form of their optical isomers, diasteriomers, and mixtures thereof, including a racemic mixture.
In addition, one or more hydrogen, carbon or other atoms of a Benzoazolylpiperazine Compound can be replaced by an isotope of the hydrogen, carbon or other atoms. Such compounds, which are encompassed by the present invention, are useful as research and diagnostic tools in metabolism pharmacokinetic studies and in binding assays.
4.3 THERAPEUTIC USES OF THE BENZOAZOLYLPIPERAZINE COMPOUNDS ha accordance with the invention, the Benzoazolylpiperazine Compounds are administered to an animal in need of treatment or prevention of pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression. ha one embodiment, an effective amount of a Benzoazolylpiperazine Compound can be used to treat or prevent any condition treatable or preventable by inhibiting VRl. Examples of conditions that are treatable or preventable by inhibiting VRl include, but are not limited to, pain, UI, an ulcer, IBD, and IBS. ha another embodiment, an effective amount of a Benzoazolylpiperazine Compound can be used to treat or prevent any condition treatable or preventable by inhibiting mGluR5. Examples of conditions that are treatable or preventable by inhibiting mGluR5 include, but are not limited to, pain, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, a pruritic condition, and psychosis. ha another embodiment, an effective amount of a Benzoazolylpiperazine Compound can be used to treat or prevent any condition treatable or preventable by inhibiting mGluRl . Examples of conditions that are treatable or preventable by inhibiting mGluRl include, but are not limited to, pain, UI, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, and depression.
The Benzoazolylpiperazine Compounds can be used to treat or prevent acute or chronic pain. Examples of pain treatable or preventable using the Benzoazolylpiperazine Compounds include, but are not limited to, cancer pain, central pain, labor pain, myocardial infarction pain, pancreatic pain, colic pain, post-operative pain, headache pain, muscle pain, pain associated with intensive care, arthritic pain, and pain associated with a periodontal disease, including gingivitis and periodontitis.
The pain to be treated or prevented can be associated with inflammation associated with an inflammatory disease, which can arise where there is an inflammation of the body tissue, and which can be a local inflammatory response and/or a systemic inflammation. For example, the Benzoazolylpiperazine Compounds can be used to treat, or prevent pain associated with inflammatory disease including, but not limited to: organ transplant rejection; reoxygenation injury resulting from organ transplantation (see Grupp et al, J. Mol, Cell Cardiol. 31:297-303 (1999)) including, but not limited to, transplantation of the heart, lung, liver, or kidney; chronic inflammatory diseases of the joints, including arthritis, rheumatoid arthritis, osteoarthritis and bone diseases associated with increased bone resorption; inflammatory bowel diseases, such as ileitis, ulcerative colitis, Barrett's syndrome, and Crohn's disease; inflammatory lung diseases, such as asthma, adult respiratory distress syndrome, and chronic obstructive airway disease; inflammatory diseases of the eye, including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis; chronic inflammatory disease of the gum, including gingivitis and periodontitis; tuberculosis; leprosy; inflammatory diseases of the kidney, including uremic complications, glomerulonephritis and nephrosis; inflammatory disease of the skin, including sclerodermatitis, psoriasis and eczema; inflammatory diseases of the central nervous system, including chronic demyelinating diseases of the nervous system, multiple sclerosis, AIDS-related neurodegeneration and Alzheimer 's disease, infectious meningitis, encephalomyelitis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and viral or autoimmune encephalitis; autoimmune diseases, including Type I and Type π diabetes mellitus; diabetic complications, including, but not limited to, diabetic cataract, glaucoma, retinopathy, nephropathy (such as microaluminuria and progressive diabetic nephropathy), polyneuropathy, mononeuropathies, autonomic neuropathy, gangrene of the feet, atherosclerotic coronary arterial disease, peripheral arterial disease, nonketotic hyperglycemic-hyperosmolar coma, foot ulcers, joint problems, and a skin or mucous membrane complication (such as an infection, a shin spot, a candidal infection or necrobiosis lipoidica diabeticorum); immune-complex vasculitis, and systemic lupus erythematosus (SLE); inflammatory disease of the heart, such as cardiomyopathy, ischemic heart disease hypercholesterolemia, and artherosclerosis; as well as various other diseases that can have significant inflammatory components, including preeclampsia, chronic liver failure, brain and spinal cord trauma, and cancer. The Benzoazolylpiperazine Compounds can also be used for inhibiting, treating, or preventing pain associated with inflammatory disease that can, for example, be a systemic inflammation of the body, exemplified by gram-positive or gram negative shock, hemonhagic or anaphylactic shock, or shock induced by cancer chemotherapy in response to pro-inflammatory cytokines, e.g., shock associated with pro-inflammatory cytokines. Such shock can be induced, e.g., by a chemotherapeutic agent that is administered as a treatment for cancer.
The Benzoazolylpiperazine Compounds can be used to treat or prevent UI. Examples of UI treatable or preventable using the Benzoazolylpiperazine Compounds include, but are not limited to, urge incontinence, stress incontinence, overflow incontinence, neurogenic incontinence, and total incontinence. The Benzoazolylpiperazine Compounds can be used to treat or prevent an ulcer. Examples of ulcers treatable or preventable using the Benzoazolylpiperazine Compounds include, but are not limited to, a duodenal ulcer, a gastric ulcer, a marginal ulcer, an esophageal ulcer, or a stress ulcer.
The Benzoazolylpiperazine Compounds can be used to treat or prevent IBD, including Crohn's disease and ulcerative colitis. The Benzoazolylpiperazine Compounds can be used to treat or prevent IBS. Examples of IBS treatable or preventable using the Benzoazolylpiperazine Compounds include, but are not limited to, spastic-colon-type IBS and constipation-predominant IBS. The Benzoazolylpiperazine Compounds can be used to treat or prevent an addictive disorder, including but not limited to, an eating disorder, an impulse-control disorder, an alcohol-related disorder, a nicotine-related disorder, an amphetamine-related disorder, a cannabis-related disorder, a cocaine-related disorder, an hallucinogen-related disorder, an inhalant-related disorders, and an opioid-related disorder, all of which are further sub-classified as listed below. Eating disorders include, but are not limited to, Bulimia Nervosa, Nonpurging
Type; Bulimia Nervosa, Purging Type; Anorexia; and Eating Disorder not otherwise specified (NOS).
Impulse control disorders include, but are not limited to, Intermittent Explosive Disorder, Kleptomania, Pyromania, Pathological Gambling, Trichotillomania, and Impulse Control Disorder not otherwise specified (NOS).
Alcohol-related disorders include, but are not limited to, Alcohol-haduced Psychotic Disorder with delusions, Alcohol Abuse, Alcohol Intoxication, Alcohol Withdrawal, Alcohol Intoxication Delirium, Alcohol Withdrawal Delirium, Alcohol-haduced Persisting Dementia, Alcohol-haduced Persisting Amnestic Disorder, Alcohol Dependence, Alcohol-hiduced Psychotic Disorder with hallucinations, Alcohol-haduced Mood Disorder, Alcohol-haduced Anxiety Disorder, Alcohol-haduced Sexual Dysfunction, Alcohol-haduced Sleep Disorder, Alcohol-Related Disorder not otherwise specified (NOS), Alcohol Intoxication, and Alcohol Withdrawal.
Nicotine-related disorders include, but are not limited to, Nicotine Dependence, Nicotine Withdrawal, and Nicotine-Related Disorder not otherwise specified (NOS).
Amphetamine-related disorders include, but are not limited to, Amphetamine Dependence, Amphetamine Abuse, Amphetamine Intoxication, Amphetamine Withdrawal, Amphetamine Intoxication Delirium, Amphetamine-haduced Psychotic Disorder with delusions, Amphetamine-hiduced Psychotic Disorders with hallucinations,
Amphetamine-Induced Mood Disorder, Amphetamine-haduced Anxiety Disorder, Amphetamine-haduced Sexual Dysfunction, Amphetamine-hiduced Sleep Disorder, Amphetamine Related Disorder not otherwise specified (NOS), Amphetamine Intoxication, and Amphetamine Withdrawal.
Cannabis-related disorders include, but are not limited to, Cannabis Dependence, Cannabis Abuse, Cannabis Intoxication, Cannabis Intoxication Delirium, Cannabis-Induced Psychotic Disorder with delusions, Cannabis-haduced Psychotic Disorder with hallucinations, Cannabis-Induced Anxiety Disorder, Cannabis Related Disorder not otherwise specified (NOS), and Cannabis Intoxication.
Cocaine-related disorders include, but are not limited to, Cocaine Dependence, Cocaine Abuse, Cocaine Intoxication, Cocaine Withdrawal, Cocaine Intoxication Delirium, Cocaine-Induced Psychotic Disorder with delusions, Cocaine-hiduced Psychotic Disorders with hallucinations, Cocaine-hiduced Mood Disorder, Cocaine- aduced Anxiety Disorder, Cocaine-haduced Sexual Dysfunction, Cocaine-Induced Sleep Disorder, Cocaine Related Disorder not otherwise specified (NOS), Cocaine Intoxication, and Cocaine Withdrawal. Hallucinogen-related disorders include, but are not limited to, Hallucinogen
Dependence, Hallucinogen Abuse, Hallucinogen Intoxication, Hallucinogen Withdrawal, Hallucinogen Intoxication Delirium, Hallucinogen-hiduced Psychotic Disorder with delusions, Hallucinogen-haduced Psychotic Disorders with hallucinations, Hallucinogen-haduced Mood Disorder, Hallucinogen-haduced Anxiety Disorder, Hallucinogen-haduced Sexual Dysfunction, Hallucinogen-haduced Sleep Disorder,
Hallucinogen Related Disorder not otherwise specified (NOS), Hallucinogen Intoxication, and Hallucinogen Persisting Perception Disorder (Flashbacks). hahalant-related disorders include, but are not limited to, Inhalant Dependence, Inhalant Abuse, Inhalant Intoxication, Inhalant Intoxication Delirium, Inhalant-haduced Psychotic Disorder with delusions, Inhalant-haduced Psychotic Disorder with hallucinations, Inhalant-Induced Anxiety Disorder, Inhalant Related Disorder not otherwise specified (NOS), and Inhalant Intoxication.
Opioid-related disorders include, but are not limited to, Opioid Dependence, Opioid Abuse, Opioid Intoxication, Opioid Intoxication Delirium, Opioid-haduced Psychotic Disorder with delusions, Opioid-haduced Psychotic Disorder with hallucinations, Opioid-haduced Anxiety Disorder, Opioid Related Disorder not otherwise specified (NOS), Opioid Intoxication, and Opioid Withdrawal.
The Benzoazolylpiperazine Compounds can be used to treat or prevent Parkinson's disease and parkinsonism and the symptoms associated with Parkinson's disease and parkinsonism, including but not limited to, bradykinesia, muscular rigidity, resting tremor, and impairment of postural balance.
The Benzoazolylpiperazine Compounds can be used to treat or prevent generalized anxiety or severe anxiety and the symptoms associated with anxiety, including but not limited to, restlessness; tension; tachycardia; dyspnea; depression, including chronic "neurotic" depression; panic disorder; agoraphobia and other specific phobias; eating disorders; and personality disorders.
The Benzoazolylpiperazine Compounds can be used to treat or prevent epilepsy, including but not limited to, partial epilepsy, generalized epilepsy, and the symptoms associated with epilepsy, including but not limited to, simple partial seizures, jacksonian seizures, complex partial (psychomotor) seizures, convulsive seizures (grand mal or tonic-clonic seizures), petit mal (absence) seizures, and status epilepticus.
The Benzoazolylpiperazine Compounds can be used to treat or prevent strokes, including but not limited to, ischemic strokes and hemonhagic strokes.
The Benzoazolylpiperazine Compounds can be used to treat or prevent a seizure, including but not limited to, infantile spasms, febrile seizures, and epileptic seizures.
The Benzoazolylpiperazine Compounds can be used to treat or prevent a pruritic condition, including but not limited to, pruritus caused by dry skin, scabies, dermatitis, herpetiformis, atopic dermatitis, pruritus vulvae et ani, miliaria, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria, urticarial eruptions of pregnancy, psoriasis, lichen planus, lichen simplex chronicus, exfoliative dermatitis, foUiculitis, bullous pemphigoid, or fiberglass dermatitis.
The Benzoazolylpiperazine Compounds can be used to treat or prevent psychosis, including but not limited to, schizophrenia, including paranoid schizophrenia, hebephrenic or disorganized schizophrenia, catatonic schizophrenia, undifferentiated schizophrenia, negative or deficit subtype schizophrenia, and non-deficit schizophrenia; a delusional disorder, including erotomanic subtype delusional disorder, grandiose subtype delusional disorder, jealous subtype delusional disorder, persecutory subtype delusional disorder, and somatic subtype delusional disorder; and brief psychosis.
The Benzoazolylpiperazine Compounds can be used to treat or prevent a cognitive disorder, including but not limited to, delirium and dementia such as multi-infarct dementia, dementia pugilistica, dimentia caused by AIDS, and dementia caused by Alzheimer's disease.
The Benzoazolylpiperazine Compounds can be used to treat or prevent a memory deficiency, including but not limited to, dissociative amnesia and dissociative fugue.
The Benzoazolylpiperazine Compounds can be used to treat or prevent restricted brain function, including but not limited to, that caused by surgery or an organ transplant, restricted blood supply to the brain, a spinal cord injury, a head injury, hypoxia, cardiac arrest, or hypoglycemia.
The Benzoazolylpiperazine Compounds can be used to treat or prevent Huntington's chorea. The Benzoazolylpiperazine Compounds can be used to treat or prevent ALS.
The Benzoazolylpiperazine Compounds can be used to treat or prevent retinopathy, including but not limited to, arteriosclerotic retinopathy, diabetic arteriosclerotic retinopathy, hypertensive retinopathy, non-proliferative retinopathy, and proliferative retinopathy. The Benzoazolylpiperazine Compounds can be used to treat or prevent a muscle spasm.
The Benzoazolylpiperazine Compounds can be used to treat or prevent a migraine including, but not limited to, migraine without aura ("common migraine"), migraine with aura ("classic migraine"), migraine without headache, basilar migraine, familial hemiplegic migraine, migrainous infarction, and migraine with prolonged aura.
The Benzoazolylpiperazine Compounds can be used to treat or prevent vomiting, including but not limited to, nausea vomiting, dry vomiting (retching), and regurgitation.
The Benzoazolylpiperazine Compounds can be used to treat or prevent dyskinesia, including but not limited to, tardive dyskinesia and biliary dyskinesia. The Benzoazolylpiperazine Compounds can be used to treat or prevent depression, including but not limited to, major depression and bipolar disorder.
Applicants believe that the Benzoazolylpiperazine Compounds are antagonists for VRl. The invention also relates to methods for inhibiting VRl function in a cell comprising contacting a cell capable of expressing VRl with an effective amount of a Benzoazolylpiperazine Compound. This method can be used in vitro, for example, as an assay to select cells that express VRl and, accordingly, are useful as part of an assay to select compounds useful for treating or preventing pain, UI, an ulcer, IBD, or IBS. The method is also useful for inhibiting VRl function in a cell in vivo, in an animal, a human in one embodiment, by contacting a cell, in an animal, with an effective amount of a Benzoazolylpiperazine Compound, ha one embodiment, the method is useful for treating or preventing pain in an animal, ha another embodiment, the method is useful for treating or preventing UI in an animal, ha another embodiment, the method is useful for treating or preventing an ulcer in an animal, ha another embodiment, the method is useful for treating or preventing IBD in an animal. In another embodiment, the method is useful for treating or preventing IBS in an animal.
Examples of tissue comprising cells capable of expressing VRl include, but are not limited to, neuronal, brain, kidney, urothelium, and bladder tissue. Methods for assaying cells that express VRl are well known in the art.
Applicants believe that the Benzoazolylpiperazine Compounds are antagonists for mGluR5.
The invention also relates to methods for inhibiting mGluR5 function in a cell comprising contacting a cell capable of expressing mGluR5 with an amount of a Benzoazolylpiperazine Compound effective to inhibit nιGluR5 function in the cell. This method can be used in vitro, for example, as an assay to select cells that express mGluR5 and, accordingly, are useful as part of an assay to select compounds useful for treating or preventing pain, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, a pruritic condition, or psychosis. The method is also useful for inhibiting mGluR5 function in a cell in vivo, in an animal, a human in one embodiment, by contacting a cell, in an animal, with an amount of a Benzoazolylpiperazine Compound effective to inhibit mGluR5 function in the cell, ha one embodiment, the method is useful for treating or preventing pain in an animal in need thereof, a another embodiment, the method is useful for treating or preventing an addictive disorder in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing Parkinson's disease in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing parkinsonism in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing anxiety in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing a pruritic condition in an animal in need thereof, hi another embodiment, the method is useful for treating or preventing psychosis in an animal in need thereof. Examples of cells capable of expressing mGluR5 are neuronal and glial cells of the central nervous system, particularly the brain, especially in the nucleus accumbens. Methods for assaying cells that express mGluR5 are well known in the art.
Applicants believe that the Benzoazolylpiperazine Compounds are antagonists for mGluRl. The invention also relates to methods for inhibiting mGluRl function in a cell comprising contacting a cell capable of expressing mGluRl with an amount of a Benzoazolylpiperazine Compound effective to inhibit mGluRl function in the cell. This method can be used in vitro, for example, as an assay to select cells that express mGluRl and, accordingly, are useful as part of an assay to select compounds useful for treating or preventing pain, UI, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression. The method is also useful for inhibiting mGluRl function in a cell in vivo, in an animal, a human in one embodiment, by contacting a cell, in an animal, with an amount of a Benzoazolylpiperazine Compound effective to inhibit mGluRl function in the cell, ha one embodiment, the method is useful for treating or preventing pain in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing UI in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing an addictive disorder in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing Parkinson's disease in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing parkinsonism in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing anxiety in an animal in need thereof, hi another embodiment, the method is useful for treating or preventing epilepsy in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing stroke in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing a seizure in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing a pruritic condition in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing psychosis in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing a cognitive disorder in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing a memory deficit in an animal in need thereof. In another embodiment, the method is useful for treating or preventing restricted brain function in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing Huntington's chorea in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing ALS in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing dementia in an animal in need thereof, h another embodiment, the method is useful for treating or preventing retinopathy in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing a muscle spasm in an animal in need thereof, hi another embodiment, the method is useful for treating or preventing a migraine in an animal in need thereof, hi another embodiment, the method is useful for treating or preventing vomiting in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing dyskinesia in an animal in need thereof, ha another embodiment, the method is useful for treating or preventing depression in an animal in need thereof. Examples of cells capable of expressing mGluRl include, but are not limited to, cerebellar Purkinje neuron cells, Purkinje cell bodies (punctate), cells of spine(s) of the cerebellum; neurons and neuropbil cells of olfactory-bulb glomeruli; cells of the superficial layer of the cerebral cortex; hippocampus cells; thalamus cells; superior colliculus cells; and spinal trigeminal nucleus cells. Methods for assaying cells that express mGluRl are well known in the art. 4.3.1 THERAPEUTIC/PROPHYLACTIC ADMINISTRATION AND COMPOSITIONS OF THE INVENTION
Due to their activity, the Benzoazolylpiperazine Compounds are advantageously useful in veterinary and human medicine. As described above, the Benzoazolylpiperazine Compounds are useful for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal in need thereof. When admimstered to an animal, the Benzoazolylpiperazine Compounds can be administered as a component of a composition that comprises a pharmaceutically acceptable vehicle. The present compositions, which comprise a Benzoazolylpiperazine Compound, can be administered orally. The Benzoazolylpiperazine Compounds of the invention can also be administered by any other convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral, rectal, and intestinal mucosa, etc.) and can be administered together with another biologically active agent. Administration can be systemic or local. Various delivery systems are known, e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc., and can be used to administer the Benzoazolylpiperazine Compound. Methods of administration include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intracerebral, intravaginal, transdermal, rectal, by inhalation, or topical, particularly to the ears, nose, eyes, or skin. The mode of administration can be left to the discretion of the practitioner, hi most instances, administration will result in the release of the Benzoazolylpiperazine Compounds into the bloodstream. ha specific embodiments, it can be desirable to administer the Benzoazolylpiperazine Compounds locally. This can be achieved, for example, and not by way of limitation, by local infusion during surgery, topical application, e.g., in conjunction with a wound dressing after surgery, by injection, by means of a catheter, by means of a suppository or enema, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibers. In certain embodiments, it can be desirable to introduce the Benzoazolylpiperazine Compounds into the central nervous system or gastrointestinal tract by any suitable route, including intraventricular, intrathecal, and epidural injection, and enema, hatraventricular injection can be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Onamaya reservoir.
Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent, or via perfusion in a fluorocarbon or synthetic pulmonary surfactant, h certain embodiments, the Benzoazolylpiperazine Compounds can be formulated as a suppository, with traditional binders and excipients such as triglycerides. h another embodiment, the Benzoazolylpiperazine Compounds can be delivered in a vesicle, in particular a liposome (see Langer, Science 249:1527-1533 (1990) and Treat et al, Liposomes in the Therapy of Infectious Disease and Cancer 311-321 and 353-365 (1989)). ha yet another embodiment, the Benzoazolylpiperazine Compounds can be delivered in a controlled-release system or sustained-release system (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)). Other controlled- or sustained-release systems discussed in the review by Langer, Science 249:1527-1533 (1990) can be used, ha one embodiment, a pump can be used (Langer, Science 249:1527-1533 (1990); Sefton, CRC Crit. Ref Biomed. Eng. 14:201 (1987);
Buchwald et al, Surgery 88:507 (1980); and Saudek et al, N Engl. J. Med. 321:574 (1989)). hi another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release (Langer and Wise eds., 1974); Controlled Drug Bioavailability, Drug Product Design and Performance (Smolen and Ball eds., 1984); Ranger and Peppas, J Macromol. Sci Rev. Macromol. Chem. 23:61 (1983); Levy et al, Science 228:190 (1985); During et al, Ann. Neurol. 25:351 (1989); and Howard et al, J. Neurosurg. 71:105 (1989)). ha yet another embodiment, a controlled- or sustained-release system can be placed in proximity of a target of the Benzoazolylpiperazine Compounds, e.g., the spinal column, brain, or gastrointestinal tract, thus requiring only a fraction of the systemic dose. ha one embodiment, the pharmaceutically acceptable vehicle is an excipient
Such a pharmaceutical excipient can be a liquid, such as water or an oil, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The pharmaceutical excipients can be saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea and the like. In addition, auxiliary, stabilizing, thickening, lubricating, and coloring agents can be used, ha one embodiment, the pharmaceutically acceptable excipients are sterile when administered to an animal. Water is a particularly useful excipient when the Benzoazolylpiperazine Compound is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid excipients, particularly for mjectable solutions. Suitable pharmaceutical excipients also include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The present compositions, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents.
The present compositions can take the form of solutions, suspensions, emulsion, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. h one embodiment, the composition is in the form of a capsule (see e.g., U.S. Patent No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington 's Pharmaceutical Sciences 1447-1676 (Alfonso R. Gennaro ed., 19th ed. 1995), incorporated herein by reference. ha one embodiment, the Benzoazolylpiperazine Compounds are formulated in accordance with routine procedures as a composition adapted for oral admimstration to human beings. Compositions for oral delivery can be in the form of tablets, lozenges, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups, or elixirs, for example. Orally administered compositions can contain one or more agents, for example, sweetening agents such as fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide a pharmaceutically palatable preparation. Moreover, where in tablet or pill form, the compositions can be coated to delay disintegration and absorption in the gastrointestinal tract thereby providing a sustained action over an extended period of time. Selectively permeable membranes surrounding an osmotically active driving compound are also suitable for orally administered compositions. In these latter platforms, fluid from the environment surrounding the capsule is imbibed by the driving compound, which swells to displace the agent or agent composition through an aperture. These delivery platforms can provide an essentially zero order delivery profile as opposed to the spiked profiles of immediate release formulations. A time-delay material such as glycerol monostearate or glycerol stearate can also be used. Oral compositions can include standard excipients such as mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, and magnesium carbonate, ha one embodiment, the excipients are of pharmaceutical grade. ha another embodiment, the Benzoazolylpiperazine Compounds can be formulated for intravenous administration. Typically, compositions for intravenous administration comprise sterile isotonic aqueous buffer. Where necessary, the compositions can also include a solubihzing agent. Compositions for intravenous administration can optionally include a local anesthetic such as lignocaine to lessen pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampule or sachette indicating the quantity of active agent. Where the Benzoazolylpiperazine Compounds are to be administered by infusion, they can be dispensed, for example, with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the Benzoazolylpiperazine Compounds are administered by injection, an ampule of sterile water for injection or saline can be provided so that the ingredients can be mixed prior to administration.
The Benzoazolylpiperazine Compounds can be administered by controlled- release or sustained-release means or by delivery devices that are well known to those of ordinary skill in the art. Examples include, but are not limited to, those described in U.S. Patent Nos.: 3,845,770; 3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; and 5,733,566, each of which is incorporated herein by reference. Such dosage forms can be used to provide controlled- or sustained-release of one or more active ingredients using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, microspheres, or a combination thereof to provide the desired release profile in varying proportions. Suitable controlled- or sustained-release formulations known to those of ordinary skill in the art, including those described herein, can be readily selected for use with the active ingredients of the invention. The invention thus encompasses single unit dosage forms suitable for oral admimstration such as, but not limited to, tablets, capsules, gelcaps, and caplets that are adapted for controlled- or sustained-release. Controlled- or sustained-release pharmaceutical compositions can have a common goal of improving drug therapy over that achieved by their non-controlled or non- sustained counterparts. In one embodiment, a controlled- or sustained-release composition comprises a mimmal amount of a Benzoazolylpiperazine Compound to cure or control the condition in a minimum amount of time. Advantages of controlled- or sustained-release compositions include extended activity of the drug, reduced dosage frequency, and increased patient compliance, hi addition, controlled- or sustained-release compositions can favorably affect the time of onset of action or other characteristics, such as blood levels of the Benzoazolylpiperazine Compound, and can thus reduce the occunence of adverse side effects.
Controlled- or sustained-release compositions can initially release an amount of a Benzoazolylpiperazine Compound that promptly produces the desired therapeutic or prophylactic effect, and gradually and continually release other amounts of the Benzoazolylpiperazine Compound to maintain this level of therapeutic or prophylactic effect over an extended period of time. To maintain a constant level of the Benzoazolylpiperazine Compound in the body, the Benzoazolylpiperazine Compound can be released from the dosage form at a rate that will replace the amount of Benzoazolylpiperazine Compound being metabolized and excreted from the body. Controlled- or sustained-release of an active ingredient can be stimulated by various conditions, including but not limited to, changes in pH, changes in temperature, concentration or availability of enzymes, concentration or availability of water, or other physiological conditions or compounds. The amount of the Benzoazolylpiperazine Compound that is effective in the treatment or prevention of pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression and can be determined by standard clinical techniques, ha addition, in vitro or in vivo assays can optionally be employed to help identify optimal dosage ranges. The precise dose to be employed will also depend on the route of administration, and the seriousness of the condition being treated and should be decided according to the judgment of the practitioner and each patient's circumstances in view of, e.g., published clinical studies. Suitable effective dosage amounts, however, range from about 10 micrograms to about 2500 milligrams about every 4 h, although they are typically about 100 mg or less, ha one embodiment, the effective dosage amount ranges from about 0.01 milligrams to about 100 milligrams of a Benzoazolylpiperazine Compound about every 4 h, in another embodiment, about 0.020 milligrams to about 50 milligrams about every 4 h, and in another embodiment, about 0.025 milligrams to about 20 milligrams about every 4 h. The effective dosage amounts described herein refer to total amounts administered; that is, if more than one Benzoazolylpiperazine Compound is administered, the effective dosage amounts conespond to the total amount administered.
Where a cell capable of expressing VRl, nιGluR5, or mGluRl is contacted with a Benzoazolylpiperazine Compound in vitro, the amount effective for inhibiting the receptor function in a cell will typically range from about 0.01 μg/L to about 5 mg/L, in one embodiment, from about 0.01 μg/L to about 2.5 mg/L, in another embodiment, from about 0.01 μg/L to about 0.5 mg/L, and in another embodiment, from about 0.01 μg/L to about 0.25 mg/L of a solution or suspension of a pharmaceutically acceptable carrier or excipient. ha one embodiment, the volume of solution or suspension is from about 1 μL to about 1 mL. ha another embodiment, the volume of solution or suspension is about 200 μL.
Where a cell capable of expressing VRl, mGluR5, or mGluRl is contacted with a Benzoazolylpiperazine Compound in vivo, the amount effective for inhibiting the receptor function in a cell will typically range from about 0.01 mg to about 100 mg/kg of body weight per day, in one embodiment, from about 0.1 mg to about 50 mg/kg body weight per day, and in another embodiment, from about 1 mg to about 20 mg/kg of body weight per day.
The Benzoazolylpiperazine Compounds can be assayed in vitro or in vivo for the desired therapeutic or prophylactic activity prior to use in humans. Animal model systems can be used to demonstrate safety and efficacy. The present methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal in need thereof can further comprise admimstering to the animal being admimstered a Benzoazolylpiperazine Compound another therapeutic agent. ha one embodiment, the other therapeutic agent is admimstered in an effective amount. The present methods for inhibiting VRl function in a cell capable of expressing VRl can further comprise contacting the cell with an effective amount of another therapeutic agent.
The present methods for inhibiting mGluR5 function in a cell capable of expressing mGluR5 can further comprise contacting the cell with an effective amount of another therapeutic agent.
The present methods for inhibiting mGluRl function in a cell capable of expressing mGluRl can further comprise contacting the cell with an effective amount of another therapeutic agent. The other therapeutic agent includes, but is not limited to, an opioid agonist, a non-opioid analgesic, a non-steroid anti-inflammatory agent, an antimigraine agent, a Cox-H inhibitor, an antiemetic, a β-adrenergic blocker, an anticonvulsant, an antidepressant, a Ca2+-channel blocker, an anticancer agent, an agent for treating or preventing UI, an agent for treating or preventing an ulcer, an agent for treating or preventing IBD, an agent for treating or preventing IBS, an agent for treating addictive disorder, an agent for treating Parkinson's disease and parkinsonism, an agent for treating anxiety, an agent for treating epilepsy, an agent for treating a stroke, an agent for treating a seizure, an agent for treating a pruritic condition, an agent for treating psychosis, an agent for treating Huntington's chorea, an agent for treating ALS, an agent for treating a cognitive disorder, an agent for treating a migraine, an agent for treating vomiting, an agent for treating dyskinesia, or an agent for treating depression, and mixtures thereof.
Effective amounts of the other therapeutic agents are well known to those skilled in the art. However, it is well within the skilled artisan's purview to determine the other therapeutic agent's optimal effective-amount range, ha one embodiment of the invention, where another therapeutic agent is admimstered to an animal, the effective amount of the Benzoazolylpiperazine Compound is less than its effective amount would be where the other therapeutic agent is not admimstered. ha this case, without being bound by theory, it is believed that the Benzoazolylpiperazine Compounds and the other therapeutic agent act synergistically to treat or prevent pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression.
Examples of useful opioid agonists include, but are not limited to, alfentanil, allylprodine, alphaprodine, anileridine, benzyhnorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethyhnethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmoφhan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevoφhanol, normethadone, naloφhine, normoφhine, noφipanone, opium, oxycodone, oxymoφhone, papaveretum, pentazocine, phenadoxone, phenomoφhan, phenazocine, phenoperidine, piminodine, piritramide, proheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts thereof, and mixtures thereof, ha certain embodiments, the opioid agonist is selected from codeine, hydromoφhone, hydrocodone, oxycodone, dihydrocodeine, dihydromoφhine, moφhine, tramadol, oxymoφhone, pharmaceutically acceptable salts thereof, and mixtures thereof. Examples of useful non-opioid analgesics include non-steroidal anti-inflammatory agents, such as aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, caφrofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid, tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam, isoxicam, and pharmaceutically acceptable salts thereof, and mixtures thereof. Other suitable non-opioid analgesics include the following, non-limiting, chemical classes of analgesic, antipyretic, nonsteroidal anti-inflammatory drugs: salicylic acid derivatives, including aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, and olsalazin; para-aminophennol derivatives including acetaminophen and phenacetin; indole and indene acetic acids, including indomethacin, sulindac, and etodolac; heteroaryl acetic acids, including tolmetin, diclofenac, and ketorolac; anthranilic acids (fenamates), including mefenamic acid and meclofenamic acid; enolic acids, including oxicams (piroxicam, tenoxicam), and pyrazolidinediones (phenylbutazone, oxyphenthartazone); and alkanones, including nabumetone. For a more detailed description of the NSAIDs, see Paul A. Insel, Analgesic-Antipyretic and Anti-inflammatory Agents and Drugs Employed in the Treatment of Gout, in Goodman & Gilman 's The Pharmacological Basis of Therapeutics 611-51 (Perry B. Molinhoff and Raymond W. Ruddon eds., 9th ed 1996) and Glen R. Hanson, Analgesic, Antipyretic and Anti-Inflammatory Drugs in Remington: The Science and Practice of Pharmacy Vol II 1196-1221 (A.R. Gennaro ed. 19th ed. 1995) which are hereby incoφorated by reference in their entireties.
Examples of useful Cox-H inhibitors and 5-lipoxygenase inhibitors, as well as combinations thereof, are described in U.S. Patent No. 6,136,839, which is hereby incoφorated by reference in its entirety. Examples of useful Cox-π inhibitors include, but are not limited to, rofecoxib and celecoxib.
Examples of useful antimigraine agents include, but are not limited to, alpiropride, dihydroergotamine, dolasetron, ergocornine, ergocorninine, ergocryptine, ergot, ergotamine, flumedroxone acetate, fonazine, lisuride, lomerizine, methysergide oxetorone, pizotyline, and mixtures thereof. The other therapeutic agent can also be an agent useful for reducing any potential side effects of a Benzoazolylpiperazine Compounds. For example, the other therapeutic agent can be an antiemetic agent. Examples of useful antiemetic agents include, but are not limited to, metoclopromide, domperidone, prochloφerazine, promethazine, chloφromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acetylleucine monoethanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride, cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinol, thiethylperazine, thioproperazine, tropisetron, and mixtures thereof.
Examples of useful β-adrenergic blockers include, but are not limited to, acebutolol, alprenolol, amosulabol, arotinolol, atenolol, befunolol, betaxolol, bevantolol, bisoprolol, bopindolol, bucumolol, bufetolol, bufuralol, bunitrolol, bupranolol, butidrine hydrochloride, butofilolol, carazolol, carteolol, carvedilol, celiprolol, cetamolol, cloranolol, dilevalol, epanolol, esmolol, indenolol, labetalol, levobunolol, mepindolol, metipranolol, metoprolol, moprolol, nadolol, nadoxolol, nebivalol, nifenalol, nipradilol, oxprenolol, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, sulfinalol, talinolol, tertatolol, tilisolol, timolol, toliprolol, and xibenolol.
Examples of useful anticonvulsants include, but are not limited to, acetylpheneturide, albutoin, aloxidone, aminoglutethimide, 4-amino-3-hydroxybutyric acid, atrolactamide, beclamide, buramate, calcium bromide, carbamazepine, cinromide, clomethiazole, clonazepam, decimemide, diethadione, dimethadione, doxenitroin, eterobarb, ethadione, ethosuximide, ethotoin, felbamate, fluoresone, gabapentin, 5-hydroxytryptophan, lamotrigine, magnesium bromide, magnesium sulfate, mephenytoin, mephobarbital, metharbital, methetoin, methsuximide, 5-methyl-5-(3-phenanthryl)-hydantoin, 3-methyl-5-phenylhydantoin, narcobarbital, nimetazepam, nitrazepam, oxcarbazepine, paramethadione, phenacemide, phenetharbital, pheneturide, phenobarbital, phensuximide, phenylmethylbarbituric acid, phenytoin, phethenylate sodium, potassium bromide, pregabaline, primidone, progabide, sodium bromide, solanum, strontium bromide, suclofenide, sulthiame, tetrantoin, tiagabine, topiramate, trimethadione, valproic acid, valpromide, vigabatrin, and zonisamide.
Examples of useful antidepressants include, but are not limited to, binedaline, caroxazone, citalopram, dimethazan, fencamine, indalpine, indeloxazine hydrocholoride, nefopam, nomifensine, oxitriptan, oxypertine, paroxetine, sertraline, thiazesim, trazodone, benmoxine, iproclozide, iproniazid, isocarboxazid, nialamide, octamoxin, phenelzine, cotinine, rolicyprine, rolipram, maprotiline, metralindole, mianserin, mirtazepine, adinazolam, amitriptyline, amitriptylinoxide, amoxapine, butriptyline, clomipramine, demexiptiline, desipramine, dibenzepin, dimetacrine, dothiepin, doxepin, fluacizine, imipramine, imipramine N-oxide, iprindole, lofepramine, melitracen, metapramine, nortriptyline, noxiptilin, opipramol, pizotyline, propizepine, protriptyline, quinupramine, tianeptine, trimipramine, adrafinil, benactyzine, bupropion, butacetin, dioxadrol, duloxetine, etoperidone, febarbamate, femoxetine, fenpentadiol, fluoxetine, fluvoxamine, hematopoφhyrin, hypericin, levophacetoperane, medifoxamine, milnacipran, minaprine, moclobemide, nefazodone, oxaflozane, piberaline, prolintane, pyrisuccideanol, ritanserin, roxindole, rubidium chloride, sulphide, tandospirone, thozalinone, tofenacin, toloxatone, tranylcypromine, L-tryptophan, venlafaxine, viloxazine, and zimeldine.
Examples of useful Ca2+-channel blockers include, but are not limited to, bepridil, clentiazem, diltiazem, fendiline, gallopamil, mibefradil, prenylamine, semotiadil, terodiline, verapamil, amlodipine, aranidipine, barnidipine, benidipine, cilnidipine, efonidipine, elgodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, isoldipine, nitrendipine, cinnarizine, flunarizine, lidoflazine, lomerizine, bencyclane, etafenone, fantofarone, and perhexiline.
Examples of useful anticancer agents include, but are not limited to, acivicin, aclarubicin, acodazole hydrochloride, acronine, adozelesin, aldesleukin, altretamine, ambomycin, ametantrone acetate, aminoglutethimide, amsacrine, anastrozole, anthramycin, asparaginase, asperlin, azacitidine, azetepa, azotomycin, batimastat, benzodepa, bicalutamide, bisantrene hydrochloride, bisnafide dimesylate, bizelesin, bleomycin sulfate, brequinar sodium, bropirimine, busulfan, cactinomycin, calusterone, caracemide, carbetimer, carboplatin, carmustine, carubicin hydrochloride, carzelesin, cedefingol, chlorambucil, cirolemycin, cisplatin, cladribine, crisnatol mesylate, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin hydrochloride, decitabine, dexormaplatin, dezaguanine, dezaguanine mesylate, diaziquone, docetaxel, doxorubicin, doxorubicin hydrochloride, droloxifene, droloxifene citrate, dromostanolone propionate, duazomycin, edafrexate, eflornithine hydrochloride, elsamitrucin, enloplatin, enpromate, epipropidine, epirubicin hydrochloride, erbulozole, esorubicin hydrochloride, estramustine, estramustine phosphate sodium, etanidazole, etoposide, etoposide phosphate, etoprine, fadrozole hydrochloride, fazarabine, fenretinide, floxuridine, fludarabine phosphate, fluorouracil, flurocitabine, fosquidone, fostriecin sodium, gemcitabine, gemcitabine hydrochloride, hydroxyurea, idarubicin hydrochloride, ifosfamide, ilmofosine, interleukin π (including recombinant interleukin H or rIL2), interferon alfa-2a, interferon alfa-2b, interferon alfa-nl , interferon alfa-n3, interferon beta-I a, interferon gamma-I b, iproplatin, irinotecan hydrochloride, lanreotide acetate, letrozole, leuprolide acetate, liarozole hydrochloride, lometrexol sodium, lomustine, losoxantrone hydiOchloride, masoprocol, maytansine, mechlorethamine hydrochloride, megestrol acetate, melengestrol acetate, melphalan, menogaril, mercaptopurine, methotrexate, methotrexate sodium, metoprine, meturedepa, mitindomide, mitocarcin, mitocromin, mitogillin, mitomalcin, mitomycin, mitosper, mitotane, mitoxantrone hydrochloride, mycophenolic acid, nocodazole, nogalamycin, ormaplatin, oxisuran, paclitaxel, pegaspargase, peliomycin, pentamustine, peplomycin sulfate, perfosfamide, pipobroman, piposulfan, piroxantrone hydrochloride, plicamycin, plomestane, porfimer sodium, porfiromycin, prednimustine, procarbazine hydrochloride, puromycin, puromycin hydrochloride, pyrazofurin, riboprine, rogletimide, safingol, safingol hydrochloride, semustine, simtrazene, sparfosate sodium, sparsomycin, spirogermanium hydrochloride, spiromustine, spiroplatin, streptonigrin, streptozocin, sulofenur, talisomycin, tecogalan sodium, tegafur, teloxantrone hydrochloride, temoporfin, teniposide, teroxirone, testolactone, thiamiprine, tliioguanine, thiotepa, tiazofurin, tirapazamine, toremifene citrate, trestolone acetate, triciribine phosphate, trimetrexate, trimetrexate glucuronate, triptorelin, tubulozole hydrochloride, uracil mustard, uredepa, vapreotide, verteporfin, vinblastine sulfate, vincristine sulfate, vindesine, vindesine sulfate, vinepidine sulfate, vinglycinate sulfate, vinleurosine sulfate, vinorelbine tartrate, vinrosidine sulfate, vinzolidine sulfate, vorozole, zeniplatin, zinostatin, zorubicin hydrochloride.
Examples of other anti-cancer drugs include, but are not limited to, 20-epi-l,25 dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; aclarubicin; acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK antagonists; altretamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing moφhogenetic protein- 1; antiandrogen, prostatic carcinoma; antiestrogen; antineoplaston; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA; arginine deaminase; asulacrine; atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; azatyrosine; baccatin derivatives; balanol; batimastat; BCR/ABL antagonists; benzochlorins; benzoylstaurosporine; beta lactam derivatives; beta-alethine; betaclamycin B; betulinic acid; bFGF inhibitor; bicalutamide; bisantrene; bisaziridinylspenaaine; bisnafide; bistratene A; bizelesin; breflate; bropirimine; budotitane; buthionine sulfoximine; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamide-amino-triazole; carboxyamidotriazole; CaRest M3; CARN 700; cartilage derived inhibitor; carzelesin; casein kinase inhibitors (ICOS); castanospermine; cecropin B; cetrorelix; chlorhas; chloroquinoxaline sulfonamide; cicaprost; cis-poφhyrin; cladribine; clomifene analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogue; conagenin; crambescidin 816; crisnatol; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnm B; deslorelin; dexamethasone; dexifosfamide; dexrazoxane; dexverapamil; diaziquone; didemnin B; didox; diethylnorspermine; dihydro-5-azacytidine; dihydrotaxol, 9-; dioxamycin; diphenyl spiromustine; docetaxel; docosanol; dolasetron; doxifluridine; droloxifene; dronabinol; duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab; eflornithine; elemene; emitefur; epirubicin; epristeride; estramustine analogue; estrogen agonists; estrogen antagonists; etanidazole; etoposide phosphate; exemestane; fadrozole; fazarabine; fenretinide; filgrastim; finasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; fonnestane; fostriecin; fotemustine; gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; hypericin; ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine; ilomastat; imidazoacridones; imiquimod; immunostimulant peptides; insulin-like growth factor-1 receptor inhibitor; interferon agonists; interferons; interleuldns; iobenguane; iododoxorubicin; ipomeanol, 4-; iroplact; irsogladine; isobengazole; isol omohalicondrin B; itasetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; lenograstim; lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting factor; leukocyte alpha interferon; leuprolide+estrogen+progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogue; lipophilic disaccharide peptide; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lurtotecan; lutetium texaphyrin; lysofylline; lytic peptides; maitansine; mannostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; menogaril; merbarone; meterelin; methioninase; metoclopramide; M1F inhibitor; mifepristone; miltefosine; mirimostim; mismatched double stranded RNA; mitoguazone; mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast growth factor-saporin; mitoxantrone; mofarotene; molgramostim; monoclonal antibody, human chorionic gonadotrophin; monophosphoryl lipid A+myobacterium cell wall sk; mopidamol; multiple drug resistance gene inhibitor; multiple tumor suppressor 1 -based therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyldinaline;
N-substituted benzamides; nafarelin; nagrestip; naloxone+pentazocine; napavin; naphteφin; nartograstim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamycin; nitric oxide modulators; nitroxide antioxidant; nitruUyn; O6-benzylguanine; octreotide; okicenone; oligonucleotides; onapristone; ondansetron; ondansetron; oracin; oral cytokine inducer; ormaplatin; osaterone; oxaliplatin; oxaunomycin; paclitaxel; paclitaxel analogues; paclitaxel derivatives; palauamine; palmitoyhhizoxin; pamidronic acid; panaxytriol; panomifene; parabactin; pazelliptine; pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin; pentrozole; perflubron; perfosfamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil; pilocaφine hydrochloride; pirarubicin; piritrexim; placetin A; placetin B; plasminogen activator inhibitor; platinum complex; platinum compounds; platinum-triamine complex; porfimer sodium; porfiromycin; prednisone; propyl bis-acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulator; protein kinase C inhibitor; protein kinase C inhibitors, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; puφurins; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonists; raltitrexed; ramosetron; ras farnesyl protein transferase inhibitors; ras inhibitors; ras-GAP inhibitor; retelliptine demethylated; rhenium Re 186 etidronate; rhizoxin; ribozymes; RU retinamide; rogletimide; rohitukine; romurtide; roquinimex; rubiginone Bl ; ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 mimetics; semustine; senescence derived inhibitor 1 ; sense oligonucleotides; signal transduction inhibitors; signal transduction modulators; single chain antigen binding protein; sizofiran; sobuzoxane; sodium borocaptate; sodium phenylacetate; solverol; somatomedin binding protein; sonermin; sparfosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem-cell division inhibitors; stipiamide; stromelysin inhibitors; sulfinosine; superactive vasoactive intestinal peptide antagonist; suradista; suramin; swainsonine; synthetic glycosaminoglycans; tallimustine; tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; temoporfin; temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine; thaliblastine; thiocoraline; thrombopoietin; thrombopoietin mimetic; thymalfasin; thymopoietin receptor agonist; thymotrinan; thyroid stimulating hormone; tin ethyl etiopuφurin; tirapazamine; titanocene bichloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitors; tyφhostins; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; vapreotide; variolin B; vector system, erythrocyte gene therapy; velaresol; veramine; verdins; verteporfin; vinorelbine; vinxaltine; vitaxin; vorozole; zanoterone; zeniplatin; zilascorb; and zinostatin stimalamer. Examples of useful therapeutic agents for treating or preventing UI include, but are not limited to, propantheline, imipramine, hyoscyamine, oxybutynin, and dicyclomine. Examples of useful therapeutic agents for treating or preventing an ulcer include, antacids such as aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, and calcium bicarbonate; sucraflate; bismuth compounds such as bismuth subsalicylate and bismuth subcitrate; H2 antagonists such as cimetidine, ranitidine, famotidine, and nizatidine;
Tt, K+ - ATPase inhibitors such as omeprazole, iansoprazole, and lansoprazole; carbenoxolone; misprostol; and antibiotics such as tefracycline, metronidazole, timidazole, clarithromycin, and amoxicillin.
Examples of useful therapeutic agents for treating or preventing IBD include, but are not limited to, anticholinergic drugs; diphenoxylate; loperamide; deodorized opium tincture; codeine; broad-spectrum antibiotics such as metronidazole; sulfasalazine; olsalazie; mesalamine; prednisone; azathioprine; mercaptopurine; and methotrexate.
Examples of useful therapeutic agents for treating or preventing IBS include, but are not limited to, propantheline; muscarine receptor antagonists such as pirenzapine, methocframine, ipratropium, tiotropium, scopolamine, methscopolamine, homatropine, homatropine methylbromide, and methantheline; and antidiareheal drugs such as diphenoxylate and loperamide. Examples of useful therapeutic agents for treating or preventing an addictive disorder include, but are not limited to, methadone, desipramine, amantadine, fluoxetine, buprenoφhine, an opiate agonist, 3-phenoxypyridine, levomethadyl acetate hydrochloride, and serotonin antagonists. Examples of useful therapeutic agents for treating or preventing Parkinson's disease and parkinsonism include, but are not limited to, carbidopa/levodopa, pergolide, bromocriptine, ropinirole, pramipexole, entacapone, tolcapone, selegiline, amantadine, and trihexyphenidyl hydrochloride.
Examples of useful therapeutic agents for treating or preventing anxiety include, but are not limited to, benzodiazepines, such as alprazolam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, demoxepam, diazepam, estazolam, flumazenil, flurazepam, halazepam, lorazepam, midazolam, nitrazepam, nordazepam, oxazepam, prazepam, quazepam, temazepam, and triazolam; non-benzodiazepine agents, such as buspirone, gepirone, ipsaprione, tiospirone, zolpicone, zolpidem, and zaleplon; franquihzers, such as barbituates, e.g., amobarbital, aprobarbital, butabarbital, butalbital, mephobarbital, methohexital, pentobarbital, phenobarbital, secobarbital, and thiopental; and propanediol carbamates, such as meprobamate and tybamate.
Examples of useful therapeutic agents for treating or preventing epilepsy include, but are not limited to, carbamazepine, ethosuximide, gabapentin, lamotrignine, phenobarbital, phenytoin, primidone, valproic acid, trimethadione, bemzodiaepines, gabapentin, lamotrigine, γ-vinyl GABA, acetazolamide, and felbamate.
Examples of useful therapeutic agents for treating or preventing stroke include, but are not limited to, anticoagulants such as heparin, agents that break up clots such as sfreptokinase or tissue plasminogen activator, agents that reduce swelling such as mannitol or corticosteroids, and acetylsalicylic acid.
Examples of useful therapeutic agents for treating or preventing a seizure include, but are not limited to, carbamazepine, ethosuximide, gabapentin, lamotrignine, phenobarbital, phenytoin, primidone, valproic acid, trimethadione, bemzodiaepines, gabapentin, lamotrigine, γ-vinyl GABA, acetazolamide, and felbamate. Examples of useful therapeutic agents for treating or preventing a pruritic condition include, but are not limited to, naltrexone; nalmefene; danazol; tricyclics such as amitriptyline, imipramine, and doxepin; antidepressants such as those given below, menthol; camphor; phenol; pramoxine; capsaicin; tar; steroids; and antihistamines.
Examples of useful therapeutic agents for treating or preventing psychosis include, but are not limited to, phenothiazines such as chloφromazine hydrochloride, mesoridazine besylate, and thoridazine hydrochloride; thioxanthenes such as chloroprothixene and thiothixene hydrochloride; clozapine; risperidone; olanzapine; quetiapine; quetiapine fumarate; haloperidol; haloperidol decanoate; loxapine succinate; molindone hydrochloride; pimozide; and ziprasidone.
Examples of useful therapeutic agents for treating or preventing Huntington's chorea include, but are not limited to, haloperidol and pimozide.
Examples of useful therapeutic agents for treating or preventing ALS include, but are not limited to, baclofen, neurotrophic factors, riluzole, tizanidine, benzodiazepines such as clonazepan and dantrolene.
Examples of useful therapeutic agents for treating or preventing cognitive disorders include, but are not limited to, agents for treating or preventing dementia such as tacrine; donepezil; ibuprofen; antipsychotic drugs such as thioridazine and haloperidol; and antidepressant drugs such as those given below.
Examples of useful therapeutic agents for treating or preventing a migraine include, but are not limited to, sumaxriptan; methysergide; ergotamine; caffeine; and beta- blockers such as propranolol, verapamil, and divalproex.
Examples of useful therapeutic agents for treating or preventing vomiting include, but are not limited to, 5-HT3 receptor antagonists such as ondansetron, dolasetron, granisetron, and fropisetron; dopamine receptor antagonists such as prochloφerazine, thiethylperazine, chloφromazin, metoclopramide, and domperidone; glucocorticoids such as dexamethasone; and benzodiazepines such as lorazepam and alprazolam.
Examples of useful therapeutic agents for treating or preventing dyskinesia include, but are not limited to, reseφine and tetrabenazine.
Examples of useful therapeutic agents for treating or preventing depression include, but are not limited to, tricyclic antidepressants such as amitryptyline, amoxapine, bupropion, clomipramine, desipramine, doxepin, imipramine, maprotilinr, nefazadone, nortriptyline, protriptyline, trazodone, trimipramine, and venlaflaxine; selective serotonin reuptake inhibitors such as fluoxetine, fluvoxamine, paroxetine, and setraline; monoamine oxidase inhibitors such as isocarboxazid, pargyline, phenelzine, and tranylcypromine; and psychostimulants such as dextroamphetamine and methylphenidate.
A Benzoazolylpiperazine Compound and the other therapeutic agent can act additively or, in one embodiment, synergistically. ha one embodiment, a
Benzoazolylpiperazine Compound is admimstered concunently with another therapeutic agent, ha one embodiment, a composition comprising an effective amount of a Benzoazolylpiperazine Compound and an effective amount of another therapeutic agent can be admimstered. Alternatively, a composition comprising an effective amount of a Benzoazolylpiperazine Compound and a different composition comprising an effective amount of another therapeutic agent can be concunently administered. In another embodiment, an effective amount of a Benzoazolylpiperazine Compound is admimstered prior or subsequent to administration of an effective amount of another therapeutic agent, ha this embodiment, the Benzoazolylpiperazine Compound is administered while the other therapeutic agent exerts its therapeutic effect, or the other therapeutic agent is admimstered while the Benzoazolylpiperazine Compound exerts its preventative or therapeutic effect for treating or preventing a Condition in an animal.
A composition of the invention is prepared by a method comprising admixing a Benzoazolylpiperazine Compound and a pharmaceutically acceptable carrier or excipient. Admixing can be accomplished using methods well known for admixing a compound (or salt) and a pharmaceutically acceptable vehicle, a one embodiment, the Benzoazolylpiperazine Compound is present in the composition in an effective amount.
4.3.2 Kits The invention encompasses kits that can simplify the admimstration of a
Benzoazolylpiperazine Compound to an animal.
A typical kit of the invention comprises a unit dosage form of a
Benzoazolylpiperazine Compound, a one embodiment, the unit dosage form is a container, which can be sterile, containing an effective amount of a Benzoazolylpiperazine Compound and a pharmaceutically acceptable vehicle. The kit can further comprise a label or printed instructions instructing the use of the Benzoazolylpiperazine Compound to treat pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, ALS, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression. The kit can also further comprise a unit dosage form of another therapeutic agent, for example, a container containing an effective amount of the other therapeutic agent, a one embodiment, the kit comprises a container containing an effective amount of a Benzoazolylpiperazine Compound and an effective amount of another therapeutic agent. Examples of other therapeutic agents include, but are not limited to, those listed above. Kits of the invention can further comprise a device that is useful for administering the unit dosage forms. Examples of such a device includes, but are not limited to, a syringe, a drip bag, a patch, an inhaler, and an enema bag.
The following examples are set forth to assist in understanding the invention and should not, of course, be construed as specifically limiting the invention described and claimed herein. Such variations of the invention, including the substitution of all equivalents now known or later developed, which would be within the purview of those skilled in the art, and changes in formulation or minor changes in experimental design, are to be considered to fall within the scope of the invention incoφorated herein.
5. EXAMPLES
5.1. Example 1: Synthesis of Benzoazolylpiperazine Compounds of Formula (la) AAM, AAS, AAQ, AAP, AYF, AYD, AZW, AZZ, AYH, AYE, AYI, AYK, AYG, AYC, AZA,
AZD. AYN. and AYM
Figure imgf000613_0001
Benzoazolylperazine Compound of Formula (la)
A solution of of 2-chloro-3-X-pyridine 1 (about 0.5M - about 1 M) and 1 eq. of 2-Q-piperazine 2 in DMSO was heated to about 140°C with stirring for about 2 to 4 h.
The resulting reaction mixture was then cooled to room temperature and the DMSO was removed under reduced pressure to provide compound 3. ha a separate flask a solution of 0.75 eq. of chloroformate 4 in dichloromethane (DCM) (0.04M) was cooled to 0°C and 0.75 eq. of 5-Z-6-Y-benzothiazol-2- ylamine 5 was slowly added to the cooled solution of chloroformate 4. The resulting reaction mixture was stirred at 0°C for 5 min. and then 5 eq. of triethylamine was added to the reaction mixture. The reaction mixture was then warmed to room temperature and concentrated under reduced pressure at 40°C to provide compound 6.
Compound 6 was dissolved in DCM (0.1M) and 1 eq. of 3 as a 1 M solution in DCM was added to the solution of compound 6 at room temperature and the resulting reaction mixture was allowed to stir for about 10 min. The reaction mixture was then concentrated under reduced pressure at 40°C to provide the Benzoazolylpiperazine Compound offormula (la). The Benzoazolylpiperazine Compound offormula (la) was purified using a silica gel column eluted with 5:95 ethyl acetate / hexane. Table XXIH lists the Benzoazolylpiperazine Compounds that were prepared according to the method of Example 1.
Table XXIII
Figure imgf000614_0001
Figure imgf000615_0001
(R)-CH3 means that the carbon atom to which the methyl group is attached is in the (R) configuration.
The identity of Compound AAM was confirmed using H1 NMR.
Compound AAM: Η NMR (400 MHz, CDC13), 58.24-8.19 (m, IH), 7.77- 7.76 (m, IH), 7.67-7.64 (m, IH), 7.57-7.54 (m, IH), 7.38-7.36 (m, IH), 6.95-6.90 (m, IH), 3.77-3.75 (m, 4H), 3.45-3.42 (m, 4H).
The identity of Compound AAS was confirmed using H1 NMR.
Compound AAS: Η NMR (400 MHz, CDC13), δlθ.17 (s, IH), 8.19-8.15 (m, IH), 7.61-7.58 (m, IH), 7.51-7.46 (m,. IH), 7.28-7.22 (m, IH), 6.98-6.95 (m, IH), 6.89-6.86 (m, IH), 4.11-4.04 (m, 2H), 3.77-3.71 (m, 4H), 3.37-3.34 (m, 4H), 1.43 (t, 3H).
The identity of Compound AAQ was confirmed using H1 NMR.
Compound AAQ: Η NMR (400MHz, CDC13): 68.22-8.19 (m, IH), 8.09- 8.05 (m, IH), 7.76-7.71 (m, IH), 7.66-7.64 (m, 2H), 6.94-6.91 (m, IH), 3.80-3.75 (m, 4H), 3.47-3.45 (m, 4H).
The identity of Compound AAP was confirmed using H1 NMR.
Compound AAP: Η NMR (CDC13), 68.22-8.20 (m, IH), 7.65-7.63 (m, IH), 7.57-7.55 (m, IH), 7.52-7.48 (m, IH), 7.22-7.18 (m, IH), 6.92-6.87 (m, IH), 3.78-3.76 (m, 4H), 3.45-3.42 (m, 4H), 2.46 (s, 3H).
The identity of Compound AYF was confirmed using H1 NMR.
Compound AYF: Η NMR (CDC13), 6 8.23-8.20 (m, IH), 7.93-7.90 (m, IH), 7.67-7.62 (m, IH), 7.54-7.50 (m, 2H), 6.95-6.91 (m, IH), 4.45 (bs, IH), 4.11-4.05 (m, IH), 3.86-3.76 (m, 2H), 3.57-3.46 (m, IH), 3.12-3.06 (m, IH), 3.02-2.94 (m, IH), 1.50 (d, 3H, J=6.8). The identity of Compound AYD was confirmed using H1 NMR and mass spectrometry.
Compound AYD: Η NMR (CDC13), 6 8.83 (br, IH), 8.24-8.20 (m, IH), 7.81-
7.74 (m, IH), 7.68-759 (m, 2H), 7.48-7.38 (m, IH), 7.33-7.24 (m, 2H + CHC13), 6.96-6.87 (m, IH), 4.55-4.43 (m, IH), 4.17-4.06 (m, IH), 3.89-3.75 (m, 2H), 3.58-3.42 (m, IH), 3.16-
2.89 (m, IH), 1.45 (d, 3H, J = 6.8 Hz). (M+l) na/z: 388.0.
The identity of Compound AZW was confirmed using H1 NMR. Compound AZW: Η NMR (CDC13), 68.49-8.45 (m, IH), 7.94-7.90 (m, IH),
7.57-7.54 (m, IH), 7.52-7.46 (m, IH), 7.22-7.18 (m, IH), 7.11-7.06 (m, IH), 4.46 (bs, IH), 4.09-4.00 (m, IH), 3.52-3.42 (m, 2H), 3.38-3.33 (m, IH), 3.25-3.19 (m, IH), 3.04-2.96 (m, IH), 1.39 (d, 3H, J=6.8).
The identity of Compound AZZ was confirmed using H1 NMR.
Compound AZZ: Η NMR (CDC13), 68.50-8.46 (m, IH), 7.94-7.91 (m, IH), 7.55 (bs, IH), 7.51-7.47 (m, IH), 7.21-7.17 (m, IH), 7.11-7.06 (m, IH), 4.45 (bs, IH), 4.09- 4.01 (m, IH), 3.53-3.45 (m, 2H), 3.41-3.34 (m, IH), 3.26-3.20 (m, IH), 3.07-2.95 (m, IH), 2.46 (s, 3H), 1.38 (d, 3H, J=6.7).
The identity of Compound AYH was confirmed using H1 NMR. Compound AYH: Η NMR (CDC13), 68.71 (bs, IH), 8.24-8.20 (m, IH), 7.67- 762 (m, IH), 7.58 (bs, IH), 7.55-7.49 (m, IH), 7.25-7.19 (m, IH), 6.94-6.89 (m, IH), 4.46 (bs, IH), 4.14-4.06 (m, IH), 3.86-3.74 (M, 2H), 3.56-3.43 (m, IH), 3.13-3.05 (m, IH), 3.03- 2.95 (m, IH), 2.47 (s, 3H), 1.64 (s, 3H), 1.47 (d, 3H, J=7.0).
The identity of Compound AYE was confirmed using H1 NMR.
Compound AYE: Η NMR (CDC13), 68.37 (bs, IH), 8.24-8.21 (m, IH), 7.77-
7.75 (m, IH), 7.67-7.64 (m, IH), 7.61-7.57 (m, IH), 7.39-7.35 (m, IH), 6.95-6.90 (m, IH), 4.40 (bs, IH), 4.15-4.01 (m, IH), 3.90-3.77 (m, IH), 3.58-3.47 (m, IH), 3.14-3.07 (m, IH),
3.05-2.96 (m, IH), 1.51 (d, 3H, J=6.8). The identity of Compound AYI was confirmed using H1 NMR.
Compound AYI: Η NMR (CDC13), 69.31 (bs, IH), 8.22-8.19 (m, IH), 8.08 (bs, IH), 7.76-7.70 (m, IH), 7.68-7.61 (m, 2H), 6.94-6.89 (m, IH), 4.46 (bs, IH), 4.11-4.02 (m, IH), 3.85-3.74 (m, 2H), 3.59-3.48 (m, IH), 3.12-3.05 (m, IH), 3.02-2.92 (m, IH), 1.49 (d, 3H, J=6.8).
The identity of Compound AYK was confirmed using H1 NMR.
Compound AYK: Η NMR (CDC13), 69.40 (bs, IH), 8.22-8.18 (m, IH), 7.64- 7.60 (m, IH), 7.57-7.51 (m,lH), 7.30-7.25 (m, 1H+CHC13), 7.03-6.97 (m, IH), 6.93-6.88 (m, IH), 4.45 (bs, IH), 4.14-4.00 (m, 3H), 3.81-3.69 (m, 2H), 3.53-3.43 (m, IH), 3.09-3.02 (m, IH), 3.00-2.91 (m, IH), 1.48-1.43 (m, 6H).
The identity of Compound AYG was confirmed using H1 NMR. Compound AYG: Η NMR (CDC13), 68.41 (bs, IH), 8.24-8.20 (m, IH), 7.68- 7.56 (m, 2H), 7.52-7.46 (m, IH), 7.18-7.11 (m, IH), 6.95-6.90 (m, IH). 4.41 (bs, IH), 4.09- 4.02 (m, IH), 3.89-3.77 (m, 2H), 3.58-3.49 (m, IH), 3.14-307 (m, IH), 3.05-2.96 (m, IH), 1.5 (d, 3H, J=6.8).
The identity of Compound AYC was confirmed using H1 NMR. Compound AYC: Η NMR (CDC13), 68.23-8.19 (m, IH), 765-7.61 (m, IH),
7.52 (bs, IH), 7.40 (bs, IH), 6.93-6.88 (m, IH), 4.50 (bs, IH), 4.17-4.06 (m, IH), 3.84-3.73 (m, 2H), 3.56-3.44 (m, IH), 3.11-3.03 (m, IH), 3.01-2.92 (m, IH), 2.36 (s, 6H), 1.48 (d., 3H, J=6.8).
The identity of Compound AZA was confirmed using H1 NMR.
Compound AZA: Η NMR (CDC13), 68.93 (bs, IH), 8.17-8.14 (m, IH), 8.00- 7.96 (m, IH), 7.77 (bs, IH), 7.60-7.53 (m, IH), 7.41-7.33 (m, IH), 4.49 (bs, IH), 4.16-4.06 (m, IH), 4.00-3.94 (m, 2H), 3.57-3.46 (m, IH), 3.19-3.11 (m, IH), 3.07-2.98 (m, IH), 1.70 (s, 3H), 1.47 (d, 3H, J=6.8).
The identity of Compound AZD was confirmed using H1 NMR. Compound AZD: Η NMR (CDC13), 68.68 (bs, IH), 8.21-8.18 (m, IH), 7.61- 7.43 (m, 3H), 7.24-7.19 (m, IH), 6.94-6.90 (m, IH), 4.45 (bs, IH), 4.13-4.04 (m, IH), 3.54- 3.41 (m, 2H), 3.37-3.32 (m, IH), 3.12-3.04 (m, IH), 3.64-2.90 (m IH), 2.46 (s, 3H), 2.35 (s, 3H), 1.48 (d, 3H, J=6.8).
The identity of Compound AYN was confirmed using H1 NMR.
Compound AYN: Η NMR (CDC13), 68.20-8.18 (m, IH), 7.64-7.59 (m, IH), 7.58-7.50 (m, IH), 7.29-7.25 (m, 1H + CHC13), 6.91-6.87 (m, IH), 4.49 (bs, IH), 4.14-4.05 (m, IH), 3.79-3.68 (m, 2H), 3.07-2.89 (m, 3H), 1.44 (d, 3H, J=6.8), 1.31 (d, 3H, =7.0).
The identity of Compound AYM was confirmed using H1 NMR.
Compound AYM: Η NMR (CDC13), 68.24-8.20 (m, IH), 7.76 (bs, IH), 7.66-7.62 (m, IH), 7.55-7.52 (m,. IH), 7.49-7.43 (m, IH), 6.94-6.89 (m, IH), 4.46 (bs, IH), 4.16-4.07 (m, IH), 3.87-3.73 (m, 2H), 3.56-3.45 (m, IH), 3.14-3.05 (m, IH), 3.04-2.91 (m, IH), 1.49 (d, 3H, J=6.8), 1.40 (s, 9H).:
5.2. Example 2: Synthesis of Benzoazolylpiperazine Compounds of Formula (lb)
BDJ and BDG
Compounds BDJ and BDG were prepared by a method analogous to that used in Example 1 except that 2, 3-dichloropyrazine was used in place of 2-chloro-3-X-pyridine 1. ha the preparation of Compound BDJ, the 2-Q-piperazine 2 was (R)-2-methylpiperidine and the 5-Z-6-Y-benzothiazol-2-ylamine 5 was 6-methyl benzothiazol-2-ylamine. ha the preparation of Compound BDG, the 2-Q-piperazine 2 was (R)-2-methylpiperidine and the 5- Z-6-Y-benzothiazol-2-ylamine 5 was 6-chloro benzothiazol-2-ylamine.
The identity of Compound BDJ was confirmed using H1 NMR. Compound BDJ: Η NMR (CDC13), 68.16-8.13 (m, IH), 7.96-7.93 (m, IH), 7.56 (bs, IH), 7.47 (bs, IH), 7.22-7.18 (m, IH), 4.56 (bs, IH), 4.19-4.13 (m, IH), 3.94-3.85 (m, 2H), 3.49-3.41 (m, IH), 3.13-3.06 (m, IH), 3.01-2.94 (m, IH), 2.45 (s, 3H), 1.41 (d, 3H, J=6.9).
The identity of Compound BDG was confirmed using H1 NMR. Compound BDG: Η NMR (CDC13), 68.66 (bs, IH), 8.17-8.15 (m, IH), 8.00-7.97 (m, IH), 7.76 (bs, IH), 7.59-7.54 (m, IH), 7.40-7.35 (m, IH), 4.47 (bs, IH), 4.16- 4.07 (m, IH), 4.02-3.92 (m, 2H), 3.57-3.48 (m, IH), 3.20-3.13 (m, IH), 3.09-2.98 (m, IH), 1.48 (d, 3H, J=6.8).
5.3. Example 3: Synthesis of Benzoazolylpiperazine Compounds of Formula (lb)
BIL. BII. and BJE
Compounds BIL BII, and BJE were prepared by a method analogous to that used in Example 1 except that 4, 5-dichlorothiadiazole was used in place of 2-chloro-3-X- pyridine 1 to make Compounds BIL and BII and 4-methyl-5-chlorothiadiazole was used to make Compound BJE. ha the preparation of Compound BIL, the 2-Q-piperazine 2 was (R)- 2-methylpiperidine and the 5-Z-6-Y-benzothiazol-2-ylamine 5 was 6-methyl benzothiazol-2- ylamine. ha the preparation of Compounds BII, and BJE the 2-Q-piperazine 2 was (R)-2- methylpiperidine and the 5-Z-6-Y-benzothiazol-2-ylamine 5 was 6-chloro benzothiazol-2- ylamine.
The identity of Compound BIL was confirmed using H1 NMR. Compound BIL: Η NMR (CDC13), 67.54 (bs, IH), 7.49-7.42 (m, IH), 7.24- 7.17 (m, IH), 4.55 (bs, IH), 4.24-4.15 (m, IH), 4.02-3.89 (m, 2H), 3.54-3.39 (m, IH), 3.21- 3.12 (m, IH), 3.11-3.02 (m, IH), 2.46 (s, 3H), 1.46 (d, 3H, J=6.8).
The identity of Compound BII was confirmed using H1 NMR. Compound BII: Η NMR (CDC13), 68.64 (bs, IH), 7.75 (bs, IH), 7.58-7.51 (m, IH), 7.41-7.34 (m, IH), 4.50 (bs, IH), 4.18-4.06 (m, IH), 4.01-3.92 (m, 2H), 3.56-3.44 (m, IH), 3.21-3.13 (m, IH), 3.12-3.04 (m, IH), 1.48 (d, 3H, J=6.8).
The identity of Compound BJE was confirmed using H1 NMR. Compound BJE: Η NMR (CDC13), 68.59 (bs, IH), 7.73 (bs, IH), 7.53-7.47 (m, IH), 7.41-7.34 (m, IH), 4.55 (bs, IH), 4.23-4.14 (m, IH), 3.59-3.46 (m, IH), 3.43-3.38 (m, IH). 3.37-3.28 (m, IH), 3.11-3.02 (m, IH), 3.00-2.90 (m, IH), 2.65 (s, 3H), 1.61 (d, 3H, J=6.8). 5.4. Example 4: Synthesis of Benzoazolylpiperazine Compound of Formula (Ha) and (Hb) CBG, CAW, CRU, CSE, DIS, DJC, DIQ, CSE, EAA, DZU, CTA, CTW, CRW, and CSB
Figure imgf000620_0001
Figure imgf000620_0002
Benzoazolylperazine Compound of
Formula (Ha) and (lib)
A solution of 2-chloro-3-X-pyridine 1 (about 0.5 M to about IM) and 1 eq. of 2-Q-piperazine 2 in DMSO was heated to about 140°C with stirring for about 2 to 4 h. The resulting reaction mixture was then cooled to room temperature and the DMSO was removed under reduced pressure to provide compound 3.
A solution of compound 3 (about 0.25 mmol - about 1 mmol) and 1 eq. of compound 7 in about 3 mL of toluene or xylene was heated at a temperature of between about 140°C and 150°C for about 3 days. The resulting reaction mixture was then concentrated under reduced pressure to provide a residue that was purified using flash chromatography (silica gel, gradient elution 2% methano DCM to 6% methano DCM).
Compound 7, wherein R10 is -H was either commercially available or obtained from commercially available compounds 8 as illustrated below
Figure imgf000621_0001
Figure imgf000621_0002
Compound 8 (about 30 mmol) and carbodiimidazole (CDI) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-aldrich.com)) (about 2 eq) was dissolved in THF (about 50 to about 150 mL) and the resulting reaction mixture was heated at reflux temperature for about 4 hours. The reaction mixture was then concentrated under reduced pressure to provide a residue. About 50 to about 100 mL of ethyl acetate or ethyl acetate / hexane (20:80 to about 40:60) was added to the residue and the resulting insoluble material was collected by filtration and washed with ethyl acetate or ethyl acetate / hexane (20:80 to about 40:60) to provide compound 9. Compound 9 was then reacted with POCl3 according to the procedure described in J. Med. Chem. 40:586-593 (1997) to provide compound 7.
Compound 7, wherein R10 is -CH3 was obtained from compound 7 wherein R10 is -H as illustrated below
Figure imgf000621_0003
8, wherein
R = _jj 8, wherein
Ri = -CH3
NaH (about 2 eq) was added to a solution of a compound of Formula 8 wherein R10 is -H in DMF at 0°C and the resulting mixture was allowed to stir and to warm to room temperature over a period of about one hour. Methyl iodide (about 1.2 eq) was then added to the solution and the resulting reaction mixture was allowed to stir for several minutes. Water was then added to the reaction mixture to produce a precipitate of compound 8 wherein R10 is -CH3 which was filtered, collected, and dried.
Table XX1N lists the Benzoazolylpiperazine Compounds that were prepared according to the method of Example A..
Table XXIV
Figure imgf000622_0001
(R)-CH3 means that the carbon atom to which the methyl group is attached is in the (R) configuration. (S)-CH3 means that the carbon atom to which the methyl group is attached is in the (S) configuration.
The identity of Compound CBG was confirmed using H1 ΝMR and mass spectrometry. Compound CBG: Η NMR (CD3OD), 6 8.21(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.77(dd, IH, Jl=1.6Hz, J2=7.6Hz); 7.34(d, IH, J=2Hz); 7.21(d, IH, Jl=0.4Hz, J2=8.4Hz); 7.14(dd, IH, Jl=2Hz, J2=8.4Hz); 7.01(dd, IH, Jl=4.8Hz, J2=7.6Hz); 3.70(m, 4H); 3.49(m, 4H); 1.37(s, 9H). MS: 370.2(M+1).
The identity of Compoxmd CAW was confirmed using H1 NMR and mass spectrometry.
Compound CAW: Η NMR (CD3OD), 6 8.25(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.82(dd, IH, Jl=1.6Hz, J2-8Hz); 7.06(dd, IH, Jl=4.8Hz, J2=7.6Hz); 3.82(m, 4H); 3.58(m, 4H); 2.38(s, 6H).
MS: 342.1(M+1).
The identity of Compound CRU wherein Q is (R)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound CRU wherein Q is (R)-CH3: Η NMR (CD3OD), 6 8.25(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.82(dd, IH, Il=2Hz, J2=8Hz); 7.07(dd, IH, Jl=4.4Hz, J2=8Hz); 4.30(m IH); 3.90(m, 4H); 3.26(dd, IH, Jl=13Hz, J2=1.6Hz); 3.17(m, IH); 2.38(s, 6H); 1.59(d, 3H, J=6.8Hz). MS: 356.1 (M+l).
The identity of Compound CRU wherein Q is (S)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound CRU wherein Q is (S)-CH3: Η NMR (CD3OD), 6 8.25(dd, IH, Jl=1.2Hz, J2=4.4Hz); 7.81(dd, IH, Jl=1.6Hz, J2=7.6Hz); 7.07(dd, IH, Jl=4.8Hz, J2=7.6Hz); 4.31(m, IH); 3.88(m, 4H); 3.26(dd, IH, Jl=3.6Hz, J2=13Hz); 3.16(m, IH); 2.38(s, 6H); 1.59(d, 3H, J=6.4Hz).
MS: 356.1(M+1).
The identity of Compound CSE wherein Q is (R)-CH3 was confirmed using H1
NMR and mass spectrometry. Compound CSE wherein Q is (R)-CH3: Η NMR (CD3OD), 6 8.22(dd, IH, Jl=1.6Hz, J2=4.8HzO; 7.78(dd, IH, Jl=1.6Hz, J2=7.6HzO; 7.33(dd, IH, Jl=0.8Hz, J2=2Hz); 7.19(dd, IH, Jl=0.8Hz, J2-8.4HzO; 7.12(dd, IH, Jl=1.6Hz, J2=8.4Hz); 7.02(dd, IH, Jl=4.8Hz, J2=8Hz); 4.37(m, IH); 3.84(m, 3H): 3.58(m, IH); 3.20(dd, IH, Jl=4Hz, J2=12Hz); 3.08(dt, IH, Jl=3.2Hz, J2=12Hz); 1.45(d, 3H, J=6.4Hz); 1.37(s, 9H).
MS: 420(M+36).
The identity of Compound DIS was confirmed using H1 NMR and mass spectrometry. Compound DIS: Η NMR (CD3OD), 6 8.23(dd, IH, Jl=l .6Hz, J2=4.8Hz);
7.78(dd, lh, Jl=2Hz, J2=8Hz); 727(bs, IH); 7.14(bs, IH); 7.02(dd, IH, Jl=4.8Hz, J2=7.6Hz); 3.69(s, 3H); 3.56(m, 4H); 3.45(m, 4H); 2.39(s, 3H); 2.35(s, 3H).
MS: 356.1CM+1).
The identity of Compound D JC was confirmed using H1 NMR and mass spectrometry.
Compound DJC: Η NMR (CD3OD), 6 8.23(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.78(dd, IH, Jl=2Hz, J2=8Hz); 7.53(dd, IH, Jl=0.8Hz, J2=2Hz); 7.31(dd, IH, Jl=1.6Hz, J2=8.4Hz); 7.26(dd, IH, Jl=0.4Hz, J2=8.4Hz); 7.02(dd, IH, Jl=4.8Hz, J2=8Hz); 3.70(s, 3H); 3.57(m, 4H); 3.47(m, ATT); 1.39(s, 9H). MS: 384.1(M+1).
The identity of Compound DIQ was confirmed using H1 NMR and mass spectrometry. Compound DIQ: Η NMR (CD3OD), 6 8.23(dd, IH, Jl=l .6Hz, J2=4.8Hz);
7.78(dd, IH, Jl=2Hz, J2=8Hz); 7.41(dd, IH, Jl=0.4Hz, J2=8.4Hz); 7.36(d, IH, J=1.2Hz); 7.29(dd, IH, Jl=1.6Hz, J2=8.4Hz); 7.02(dd, IH, Jl=4.8Hz, J2=7.6Hz); 3.70(s, 3H); 3.57(m, 4H); 3.47(m, 4H); 1.41(s, 9H).
MS: 384.1(M+1). The identity of Compound CSE wherein Q is (S)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound CSE wherein Q is (S)-CH3: !H NMR (CD3OD), 6 8.22(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.78(dd, IH, Jl=1.6Hz, J2=7.6Hz); 7.34(d, IH, J=1.6Hz); 7.20(d, IH, J=8.4Hz); 7.13(dd, IH, Jl=2Hz, J2=8.4Hz); 7.02(dd, IH, Jl=4.8Hz, J2=8Hz); 4.36(m, IH); 3.85(m, 3H); 3.60(dt, IH, Il=2.8Hz, J2=12Hz); 3.20(dd, IH, Jl=4Hz, J2=12Hz); 3.08(dt, IH, Jl=3.2Hz, J2=13Hz); 1.45(d, 3H, J=6.4Hz); 1.37(s, 9H).
MS: 420(M+36).
The identity of Compound EAA wherein Q is (R)-CH3 was confirmed using
H1 NMR and mass spectrometry.
Compound EAA wherein Q is (R)-CH3: Η NMR (DMSO d6), 6 8.23(dd, IH, Jl=1.6Hz, J2=2.8Hz); 7.63(dd, IH, Jl=1.6Hz, J2=7.6Hz); 7.61(d, IH, Jl=8.4Hz); 7.32(dd, IH, J=2Hz, J2=8Hz); 7.26(dd, IH, Jl=1.6Hz, J2=8 Hz); 6.90(dd, IH, Jl=4.8Hz, J2=8Hz); 3.80(m, IH); 3.70(s, 3H); 3.69(dd, IH, Jl=2.8Hz, J2=12Hz); 3.63(m, IH); 3.45(m, 2H); 3.35(m, IH); 3.24(dd, IH, Jl=7.6Hz, J2=12Hz); 1.43(s, 9H); 1.20(d, 3H, J=6.4Hz). MS: 398.1(M+1).
The identity of Compound DZO wherein Q is (R)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound DZO wherein Q is (R)-CH3: Η NMR (DMSO d6), 6 8.23(dd, IH, Jl=2Hz, J2=4.8Hz); 7.75(d); 7.63(dd, IH, Jl=2 Hz, J2=7.6Hz); 7.32(dd, IH, Jl=2Hz, J2=8.4Hz); 7.20(d, IH, J=8.4Hz); 6.89(dd, IH, Jl=4.8Hz, J2=7.6Hz); 3.82(m, IH); 3.68(s, 3H); 3.68(m, IH); 3.61(m, IH); 3.48(m, 2H); 3.37(m, IH); 3.28(dd, IH, Jl=8Hz, J2=12Hz); 1.41(s, 9H); 1.22(d, 3H, J=6.4Hz). MS: 398.3(M+1).
The identity of Compound CTA wherein Q is (R)-CH3 was confirmed using H1 NMR and mass spectrometry. Compound CTA wherein Q is (R)-CH3: Η NMR (CDC13), 6 8.17(d,lH,
J=4.8Hz); 7.44(d, IH, J=7.6Hz); 7.42(s, IH); 7.27(d, IH, J=8.4Hz); 7.13(d, IH, J=8.4Hz); 6.91(dd, IH, Jl=4.8Hz, J2=7.2Hz); 4.42(m, IH); 3.97(d, IH, J=12Hz); 3.62(dt, IH, Jl=3.2Hz, J2=12Hz); 3.47(d, IH, J=12Hz); 3.33(d, IH, J=13Hz); 3.18(dd, IH, Jl=3.2Hz, J2=12Hz); 3.06(dt, IH, Jl=2.8Hz, J2=12Hz); 2.32(s, 3H); 1.45(d, 3H, J=6.8Hz); 1.33(s, 9H).
MS: 364.2(M+1).
The identity of Compound CTW wherein Q is (R)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound CTW wherein Q is (R)-CH3: Η NMR (CDC13), 6 8.49(d, IH, J=4.8Hz); 7.93(dd, IH, Jl=1.6 Hz, J2=8.0Hz); 7.42(s, IH); 7.26(d, IH, J=8.4Hz); 7.14(dd, IH, Jl=1.6Hz, J2=8.4Hz); 7.08(dd, IH, Jl=4.8Hz, J2=8.0Hz); 4.37(m, IH); 3.89(d, IH, J=12Hz); 3.64(dt, IH, Jl=3.2Hz, J2=12Hz); 3.56(d, IH, J=13Hz); 3.45(d, IH, J=13Hz); 3.37(dd, IH, Jl=3.6Hz, J2=12Hz); 3.17(dt, IH, Jl=3.2Hz, J2=12Hz); 1.39(d, 3H, J=6.8Hz); 1.35(s, 9H).
MS: 418.2(M+1).
The identity of Compound CRW wherein Q is (R)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound CRW wherein Q is (R)-CH3: Η NMR (CD3OD), 6 8.21(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.78(dd, IH, Jl=1.6Hz, J2=7.6Hz); 7.24(s, IH); 7.20(d, IH, J=8Hz); 7.02(dd, IH, Jl=4.8Hz, J2=8Hz); 7.01(d, IH, J=8Hz); 4.36(m, IH); 3.86(m, 3H); 3.62(dt, IH, JT=3.2Hz, J2=12Hz); 3.18(dd, IH, Jl=2.8Hz, J2=13Hz); 3.07(dt, IH, Jl=3.2Hz, J2=13Hz); 1.46(d, 3H, J=6.8Hz).
MS: 362.1 (M+l).
The identity of Compound CSB wherein Q is (R)-CH3 was confirmed using H1
NMR and mass spectrometry.
Compound CSB wherein Q is (R)-CH3: Η NMR (CD3OD), 6 8.24(dd, IH, Jl=1.8Hz, J2=4.8Hz); 7.80(dd, IH, Jl=1.8Hz, J2=7.9Hz); 4.31(m, IH); 3.91(m, 2H); 3.80(dt, IH, Jl=3.5Hz, J2=12Hz); 3.25(dd, IH, Jl=3.2Hz, J2=12Hz); 3.15(dt, IH, Jl=4.0Hz, J2=12Hz); 1.56(d, 3H, J=6.6Hz). MS: 358.1(M+1). 5.5. Example 5: Synthesis of Benzoazolylpiperazine Compound of Formula (lib) DBM
Compound DBM wherein R3 is (R)-CH3 was prepared by a method analogous to that used in Example 4 except that 4, 5-dichlorothiadiazole was used in place of 2-chloro- 3-X-pyridine 1 and the 2-Q-piperazine 2 was 2-(R)-methylpiperazine and the 5-Z-6-Y-2- chloro- 1-H-benzoimidazole 7 was 6-tert-butyl-2-chloro-l-H-benzoimidazole.
The identity of Compound DBM wherein Q is (R)-CΗ3 was confirmed using H1 NMR and mass spectrometry.
Compound DBM wherein Q is (R)-CH3: Η NMR (CD3OD), 6 7.34(s, IH); 7.20(d, IH, J=8.4Hz); 7.13(dd, IH, Jl=1.6Hz, J2=8.4Hz); 4.38(m, IH); 4.05(bd, 2H, J=12Hz ); 3.90(bd, IH, J=13Hz); 3.58(dt, IH, Jl=3.6Hz, J2=12Hz); 3.27(dd, IH, Jl=3.6Hz, J2=12Hz); 3.20(dt, IH, Jl=3.6Hz, J2=12Hz); 1.43(d, 3H, J=6.4Hz); 1.37(s, 9H).
MS: 391.1(M+1).
5.6. Example 6: Synthesis of Benzoazolylpiperazine Compound of Formula 10 Benzoazolylpiperazine compound of Formula 10
Figure imgf000627_0001
10 was prepared by a method analogous to that used in Example 4 using compound 7 wherein Y is -CH3 and Z is -CH(CH3)2 and 2-(R)-methylpiperazine for the 2-Q-piperazine 2.
The identity of Compound 10 wherein Q is (R)-CH3 was confirmed using H1
NMR and mass spectrometry. Compound 10 wherein Q is (R)-CH3: Η NMR (CD3OD), 6 8.22(dd, IH, Jl=1.8Hz, J2=4.9Hz); 7.78(dd, IH, Jl=1.6Hz, J2=8.0z); 7.20(s, IH); 7.04(dd, IH, Jl=4.9Hz, J2=7.7Hz); 4.35(m, IH); 3.85(m, 3H); 3.62(dt, IH, Jl=3.3Hz, J2=12Hz); 3.21(m, 2H); 3.06(dt, IH, Jl=4.0Hz, J2=13Hz); 2.40(s, 3H); 1.47(d, 3H, J=6.8Hz); 1.27(d, 6H, J=6.8Hz). MS: 384.1(M+1).
5.7. Example 7: Synthesis of Benzoazolylpiperazine Compound of Formula (Hla) FUY, and EXG
Figure imgf000628_0001
Benzoazolylperazine Compound of Formula (Ilia)
Compound 3 (about 1 mmol), prepared as described above in Example 5.1 and 1 eq. of compound 11 were dissolved in toluene or p-xylene (about 0.5 to about 1 mL) and the resulting reaction mixture was heated in a sealed tube at a temperature of about 150°C for about 24 h. The reaction mixture was then concentrated under reduced pressure to provide a residue. The resulting residue was purified using flash chromatography (silica gel, 5% methanol :DCM) to provide the Benzoazolylpiperazine Compounds offormula (ffla). Compound 11 was obtained as described below
Figure imgf000628_0002
13 11 12 x
Compound 12 (about 15 to about 20 mmol) and 1 eq. of compound 13, were dissolved in ethanol (about 30 to about 40 mL) and the resulting reaction mixture heated at reflux temperature for about 5 h. The reaction mixture was then concentrated under reduced pressure to provide a residue that was diluted with water (about 30 mL) and acidified with acetic acid to a pH value of about 6. The aqueous mixture was extracted with ethyl acetate, the ethyl acetate dried (N-^SO^, and the solvent removed under reduced pressure to provide compound 7 that was used without further purification.
Table XXV lists the Benzoazolylpiperazine Compounds that were prepared according to the method of Example 7.
Table XXV
Figure imgf000629_0001
(R)-CH3 means that the carbon atom to which the methyl group is attached is in the (R) configuration.
The identity of Compound FUY was confirmed using H1 NMR and mass spectrometry.
Compound FUY: Η NMR (CDC13), 6 8.23(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.65(dd, IH, Jl=2Hz, J2=7.6Hz); 7.47(d, IH, J=2Hz); 7.20(d, IH, J=8.4Hz); 7.10(dd, IH, Jl=2Hz, J2=8.4Hz); 6.91(dd, IH, Jl=4.8Hz, J2=8Hz); 4.60(m, IH); 4.60(d, IH, J=13Hz); 3.84(m, 2H); 3.67(dt, IH, Jl=3.6Hz, J2=13Hz); 3.17(dd, IH, Jl=4Hz, J2=12Hz); 3.08(dt(lH, Jl=3.2Hz, J2=12Hz); 1.52(d, 3H, J=6.8Hz); 1.37(s, 9H).
MS: 385.2(M+1).
The identity of Compound EXG wherein Q is (R)-CH3 was confirmed using H1 NMR and mass spectrometry.
Compound EXG: Η NMR (CDC13), 6 8.23(dd, IH, Jl=1.6Hz, J2=4.8Hz); 7.65(dd, IH, Jl=2Hz, J2=7.6Hz); 7.46(d, IH, J=1.6Hz); 7.20(dd, IH, Jl=0.4Hz, J2=8.4Hz); 7.10(dd, IH, Jl=2Hz, J2=8.4Hz);6.91(dd, IH, Jl=5.2Hz, J2=7.6Hz); 3.88(m, 4H); 3.50(m, 4H); 1.37(s, 9H).
MS: 371.1(M+1). 5.8. Example 8: Synthesis of Benzoazolylpiperazine Compound of Formula (Hla)
FIU
Compound FIU was prepared by a method analogous to that used in Example
1 except that 5-chloro-benzooxoazol-2-ylamine was used in place of the 5-Z-6-Y- benzothiazol-2-ylamine.
The identity of Compound FIU was confirmed using H1 NMR. Compound FIU: Η NMR (CDC13), 611.45 (bs, IH), 8.23-8.18 (m, IH), 7.66-7.61 (m, IH), 7.25-7.21 (m, IH), 7.18-7.12 (m, IH), 6.92-6.86 (m, IH), 5.06-4.71 (m, IH), 4.67-4.32 (m, IH), 3.87-3.72 (m, 2H), 3.56-3.29 (m, IH), 3.07-2.86 (m, 2H), 1.45 (d, 3H, J=6.8).
5.9. Example 9: Synthesis of Benzoazolylpiperazine Compound of Formula 14
Figure imgf000630_0001
14 2-Amino-6-methyl-benzothiazole 15 (2.0 mmol, 328 mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-aldrich.com)) and 1,1'- thiocarbonyldiimidazole (2.0 mmol, 356 mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-aldrich.com)) were suspended in DMSO (3 mL). 4-Dimethyl- aminopyridine (30 mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma-aldrich.com)) was then added to the suspension and the resulting reaction mixture heated to 100°C and stined at 100°C for about 6 hours. The reaction mixture was then cooled to room temperature and (R)-4-(3-chloro-2-pyridinyl)-2-methylpiperazine (2.0 mmol, 422 mg) (commercially available from Sigma-Aldrich, St. Louis, MO (www.sigma- aldrich.com)) was added to the reaction mixture. The reaction mixture was heated to 100°C and stirred at 100°C for 16 hours. The solvent was then removed under reduced pressure to provide a residue that was purified using flash chromatography on a silica column eluted with ethyl acetate /hexane (gradient elution from 20:80 ethyl acetate /hexane to 10:90 ethyl acetate /hexane) to provide compound 14 as a yellow solid.
The identity of Compound 14 was confirmed using H1 NMR. Compound 14: Η NMR (CDC13), 8.21 (IH, dd, J=1.6, 4.7 Hz), 7.63 (IH, dd, J=1.6, 7.8 Hz), 7.40 (IH, d, J=0.5 Hz), 7.18 (2H, d, J=0.5 Hz), 6.89 (IH, dd, J=4.7, 7.8 Hz), 5.62 (IH, br), 5.27 (m, IH), 3.84 (2H, t, J=10.6 Hz), 3.50 (IH, dt, J=2.9, 15.3 Hz), 3.08 (IH, dd, J=3.6, 12.6 Hz), 3.00 (IH, dt, J=3.3, 15.3 Hz), 2.44 (3H, s), 1.48 (3H, d, J=7.2 Hz) ppm.
(M+l) m/z: 418.0.
5.10. Example 10: Synthesis of Benzoazolylpiperazine Compound GIQ
Figure imgf000632_0001
Compound 17 (5 g, 30.7 mmol) and piperazine 2 (3.1 g, 30.7 mmol) were dissolved in 18 mL of DMSO and stined at 100°C for about 3 h. The reaction mixture was then cooled to room temperature and the solvent removed under reduced pressure to provide a mixture of compounds 18 and 19.
Figure imgf000633_0001
A solution of 6-fluoro-benzothiazol-2-ylamine 20 (3.7 g, 23.0 mmol) in DCM (15 mL) was added portionwise to a cooled solution of chloroformate 4. The resulting reaction mixture was stined for 5 min. and 10 mL of triethylamine was added to the solution. The reaction mixture was then allowed to warm to room temperature and concentrated under reduced pressure at about 40 °C to provide the compound offormula 21. The compound offormula 21 was redissolved in DCM (30 mL) and to the resulting solution was added the mixture of compounds 18 and 19, prepared as described above, in DCM (10 mL). The resulting reaction mixture was allowed to stir for 5 min. and the solvent was removed under reduced pressure to provide a residue comprising Compound GIO and a Benzoazolylpiperazine Compound of Formula 22. The residue was purified using a silica gel column eluted with 5:95 ethyl acetate: hexane to provide 0.69 g of Compound GIO.
5.11. Example 11; Binding of Benzoazolylpiperazine Compounds to mGluR5
The following assay can be used to demonstrates Benzoazolylpiperazine Compounds that bind to and modulate the activity of mGluR5.
Cell cultures: Primary glial cultures are prepared from cortices of Sprague-Dawley 18 days old embryos. The cortices are dissected and then dissociated by trituration. The resulting cell homogenate is plated onto poly-D-lysine precoated T175 flasks (BIOCOAT, commercially available from Becton Dickinson and Company h e. of Franklin Lakes, NJ ) in Dulbelcco's Modified Eagle's Medium ("DMEM," pH 7.4), buffered with 25 mM HEPES, and supplemented with 15% fetal calf serum ("FCS," commercially available from Hyclone Laboratories frac. of Omaha, NE ), and incubated at 37°C and 5% CO2. After 24 hours, FCS supplementation is reduced to 10%. On day six, oligodendrocytes and microglia are removed by strongly tapping the sides of the flasks. One day following this purification step, secondary astrocyte cultures are established by subplating onto 96 poly-D-lysine precoated T175 flasks (BIOCOAT) at a density of 65,000 cells/well in DMEM and 10% FCS. After 24 hours, the astrocytes are washed with serum free medium and then cultured in DMEM, without glutamate, supplemented with 0.5% FCS, 20 mM HEPES, 10 ng/naL epidermal growth factor ("EGF"), 1 mM sodium pyruvate, and IX penicillin/streptomycin at pH 7.5 for 3 to 5 days at 37°C and 5% CO2 The procedure allows the expression of the mGluR5 receptor by astrocytes, as demonstrated by S. Miller et al, J. Neuroscience 15(9):6103-6109 (1995).
Assay Protocol: After 3-5 days incubation with EGF, the astrocytes are washed with 127 mM NaCl, 5 mM KC1, 2 mM MgCl2, 700 mM NaH2PO4, 2 mM CaCl2, 5 mM NaHCO3, 8 mM HEPES, 10 mM Glucose at pH 7.4 ("Assay Buffer") and loaded with the dye Fluo-4 (commercially available from Molecular Probes frac. of Eugene, OR) using 0.1 mL of Assay Buffer containing Fluo-4 (3 mM final). After 90 minutes of dye loading, the cells are then washed twice with 0.2 mL Assay Buffer and resuspended in 0.1 mL of Assay Buffer. The plates containing the astrocytes are then fransfened to a Fluorometric Imaging Plate reader (commercially available from Molecular Devices Corporation of Sunnyvale, CA) for the assessment of calcium mobilization flux in the presence of glutamate and in the presence or absence of antagonist. After monitoring fluorescence for 15 seconds to establish a base line, DMSO solutions containing various concentrations of a Benzoazolylpiperazine Compound diluted in Assay Buffer (0.05 mL of 4X dilutions for competition curves) are added to the cell plate and fluorescence is monitored for 2 minutes. 0.05 mL of a 4X glutamate solution
(agonist) is then added to each well to provide a final glutamate concentration in each well of 10 mM. Plate fluorescence is then monitored for an additional 60 seconds after agonist addition. The final DMSO concentration in the assay is 1.0%. In each experiment, fluorescence is monitored as a function of time and the data analyzed using Microsoft Excel and GraphPad Prism. Dose-response curves are fit using a non-linear regression to determine IC50 value, ha each experiment, each data point is determined two times. The assay results will demonstrate Benzoazolylpiperazine Compounds that bind to and modulate the activity of mGluR5.
5.12. Example 12: In Vivo Assays for Prevention or Treatment of Pain
Test Animals: Each experiment uses rats weighing between 200-260 g at the start of the experiment. The rats are group-housed and have free access to food and water at all times, except prior to oral administration of a Benzoazolylpiperazine Compound when food is removed for 16 hours before dosing. A control group acts as a comparison to rats treated with a Benzoazolylpiperazine Compound. The control group is administered the carrier for the Benzoazolylpiperazine Compound. The volume of carrier administered to the control group is the same as the volume of carrier and Benzoazolylpiperazine Compound admimstered to the test group.
Acute Pain: To assess the actions of the Benzoazolylpiperazine Compounds for the treatment or prevention of acute pain the rat tail flick test can be used. Rats are placed inside a cotton pouch and the tail exposed to a focused beam of radiant heat at a point 3 cm from the tip using a tail flick unit (Model 7360, commercially available from Ugo Basile of Italy). Tail flick latencies are defined as the interval between the onset of the thermal stimulus and the flick of the tail. Animals not responding within 15 seconds are removed from the tail flick unit and assigned a withdrawal latency of 15 seconds. Tail flick latencies are measured immediately before (pre-treatment) and 1, 3, and 6 hours following administration of a Benzoazolylpiperazine Compound. Data are expressed as tail flick latency(s) and the percentage of the maximal possible effect (% MPE), i.e., 15 seconds, is calculated as follows:
[ (post administration latency) - (pre-administration latency) ] % MPE = x 100
(15 s pre-administration latency)
The rat tail flick test is described in F.E. D'Amour et al, "A Method for Determimng Loss of Pain Sensation," J. Pharmacol Exp. Ther. 72:74-79 (1941). The results will demonstrate Benzoazolylpiperazine Compounds that are useful for treating or preventing acute pain. Acute pain can also be assessed by measuring the animal's response to noxious mechanical stimuli by determining the paw withdrawal threshold (PWT), as described below.
Inflammatory Pain: To assess the actions of the Benzoazolylpiperazine Compounds for the treatment or prevention of inflammatory pain the Freund's complete adjuvant (FCA) model of inflammatory pain is used. FCA-induced inflammation of the rat hind paw is associated with the development of persistent inflammatory mechanical hyperalgesia and provides reliable prediction of the anti-hyperalgesic action of clinically useful analgesic drugs (L. Bartho et al, "Involvement of Capsaicin-sensitive Neurones in Hyperalgesia and Enhanced Opioid Antinociception in haflammation," Naunyn-
Schmiedeberg's Archives of Pharmacology 342:666-670 (1990)). The left hind paw of each animal is administered a 50 μL intraplantar injection of 100% FCA. 24 hour post injection, the animal is assessed for response to noxious mechanical stimuli by determining the PWT, as described below. Rats are then administered a single injection of 1, 3, 10 or 30 mg/Kg of either a Benzoazolylpiperazine Compound, 30 mg/Kg indomethacin or carrier. Responses to noxious mechanical stimuli are then determined 2, 4, 6, and 24 hours post administration. Percentage reversal of hyperalgesia for each animal is defined as:
[ (post administration PWT) - (pre-administration PWT) ]
% Reversal = x 100 (Baseline pre-administration PWT)
The results will demonstrate Benzoazolylpiperazine Compounds that are useful for treating or preventing inflammatory pain.
Neuropathic Pain: To assess the actions of the Benzoazolylpiperazine Compounds for the treatment or prevention of neuropathic pain either the Seltzer model or the Chung model can be used. ha the Seltzer model, the partial sciatic nerve ligation model of neuropathic pain is used to produce neuropathic hyperalgesia in rats (Z. Seltzer et al, "A Novel Behavioral Model of Neuropathic Pain Disorders Produced in Rats by Partial Sciatic Nerve Injury," Pain 43:205-218 (1990)). Partial ligation of the left sciatic nerve is performed under enflurane/O2 inhalation anaesthesia. Following induction of anesthesia, the left thigh of the rat is shaved and the sciatic nerve exposed at high thigh level through a small incision and is carefully cleared of sunounding connective tissues at a site near the trocanther just distal to the point at which the posterior biceps semitendinosus nerve branches off of the common sciatic nerve. A 7-0 silk suture is inserted into the nerve with a 3/8 curved, reversed-cutting mini-needle and tightly ligated so that the dorsal 1/3 to 5 of the nerve thickness is held within the ligature. The wound is closed with a single muscle suture (7-0 silk) and a Michelle clip. Following surgery, the wound area is dusted with antibiotic powder. Sham-treated rats undergo an identical surgical procedure except that the sciatic nerve is not manipulated. Following surgery, animals are weighed and placed on a warm pad until they recover from anesthesia. Animals are then returned to their home cages until behavioral testing begins. The animal is assessed for response to noxious mechanical stimuli by determining PWT, as described below, immediately prior to and 1, 3, and 6 hours after drug admimstration for both the left rear paw and right rear paw of the animal. Percentage reversal of neuropathic hyperalgesia is defined as:
% reversal = 100 - [(right pre-administration PWT- left post-administration PWT) / ( right pre-administration PWT-left pre-administration PWT)] x 100.
ha the Chung model, the spinal nerve ligation model of neuropathic pain is used to produce mechanical hyperalgesia, themal hyperalgesia and tactile allodynia in rats. Surgery is performed under isoflurane/O2 inhalation anaesthesia. Following induction of anaesthesia a 3 cm incision is made and the left paraspinal muscles are separated from the spinous process at the L4 - S2 levels. The L6 transverse process is carefully removed with a pair of small rongeurs to identify visually the L4 - L6 spinal nerves. The left L5 (or L5 and L6) spinal nerve(s) is isolated and tightly ligated with silk thread. A complete hemostasis is confirmed and the wound is sutured using non-absorbable sutures, such as nylon sutures or stainless steel staples. Sham-treated rats undergo an identical surgical procedure except that the spinal nerve(s) is not manipulated. Following surgery animals are weighed, administered a subcutaneous (s.c.) injection of saline or ringers lactate, the wound area is dusted with antibiotic powder and they are kept on a warm pad until they recover from the anesthesia. Animals are then be returned to their home cages until behavioral testing begins. The animals are assessed for response to noxious mechanical stimuli by determining PWT, as described below, immediately prior to and 1, 3, and 5 hours after being admimstered a Benzoazolylpiperazine Compound for both the left rear paw and right rear paw of the animal. The animal can also be assessed for response to noxious thermal stimuli or for tactile allodynia, as described below. The Chung model for neuropathic pain is described in S.H. Kim, "An Experimental Model for Peripheral Neuropathy Produced by Segmental Spinal Nerve Ligation in the Rat," Pain 50(3):355-363 (1992). The results show demonstrate Benzoazolylpiperazine Compounds that are useful for treating or preventing neuropathic pain. Response to Mechanical Stimuli as an Assessment of Mechanical Hyperalgesia: The paw pressure assay can be used to assess mechanical hyperalgesia. For this assay, hind paw withdrawal thresholds (PWT) to a noxious mechanical stimulus are determined using an analgesymeter (Model 7200, commercially available from Ugo Basile of Italy) as described in C. Stein, "Unilateral Inflammation of the Hindpaw in Rats as a Model of Prolonged Noxious Stimulation: Alterations in Behavior and Nociceptive Thresholds," Pharmacology Biochemistry and Behavior 31 :451-455 (1988). The maximum weight that can be applied to the hind paw is set at 250 g and the end point is taken as complete withdrawal of the paw. PWT is determined once for each rat at each time point and only the affected (ipsilateral) paw is tested.
Response to Thermal Stimuli as an Assessment of Thermal Hyperalgesia: The plantar test can be used to assess thermal hyperalgesia. For this test, hind paw withdrawal latencies to a noxious thermal stimulus are determined using a plantar test apparatus (commercially available from Ugo Basile of Italy) following the technique described by K. Hargreaves et al. , "A New and Sensitive Method for Measuring Thermal Nociception in Cutaneous Hyperalgesia," Pain 32(l):77-88 (1988). The maximum exposure time is set at 32 seconds to avoid tissue damage and any directed paw withdrawal from the heat source is taken as the end point. Three latencies are determined at each time point and averaged. Only the affected (ipsilateral) paw is tested. Assessment of Tactile Allodynia: To assess tactile allodynia, rats are placed in clear, plexiglass compartments with a wire mesh floor and allowed to habituate for a period of at least 15 minutes. After habituation, a series of von Frey monofilaments are presented to the plantar surface of the left (operated) foot of each rat. The series of von Frey monofilaments consists of six monofilaments of increasing diameter, with the smallest diameter fiber presented first. Five trials are conducted with each filament with each trial separated by approximately 2 minutes. Each presentation lasts for a period of 4-8 seconds or until a nociceptive withdrawal behavior is observed. Flinching, paw withdrawal or licking of the paw are considered nociceptive behavioral responses. 5.13 Example 13: In Vivo Assays for Prevention or Treatment of Anxiety
The elevated plus maze test or the shock-probe burying test can be used to assess the anxiolytic activity of Benzoazolylpiperazine Compounds in rats or mice.
The Elevated Plus Maze Test: The elevated plus maze consists of a platform with 4 arms, two open and two closed (50x10x50 cm enclosed with an open roof). Rats (or mice) are placed in the center of the platform, at the crossroad of the 4 arms, facing one of the closed arms. Time spent in the open arms vs the closed arms and number of open arm entries during the testing period are recorded. This test is conducted prior to drug admimstration and again after drug administration. Test results are expressed as the mean time spent in open arms and the mean number of entries into open arms. Known anxiolytic drugs increase both the time spent in open amis and number of open arm entries. The elevated plus maze test is described in D. Treit, "Animal Models for the Study of Anti-anxiety Agents: A Review," Neuroscience & Biobehavioral Reviews 9(2):203-222 (1985).
The Shock-Probe Burying Test: For the shock-probe burying test the testing apparatus consists of a plexiglass box measuring 40x30x40 cm, evenly covered with approximately 5 cm of bedding material (odor absorbent kitty litter) with a small hole in one end through which a shock probe (6.5 cm long and 0.5 cm in diameter) is inserted. The plexiglass shock probe is helically wrapped with two copper wires through which an electric cunent is administered. The current is set at 2 naA. Rats are habituated to the testing apparatus for 30 min on 4 consecutive days without the shock probe in the box. On test day, rats are placed in one comer of the test chamber following drug admimstration. The probe is not electrified until the rat touches it with its snout or fore paws, at which point the rat receives a brief 2 naA shock. The 15 min testing period begins once the rat receives its first shock and the probe remains electrified for the remainder of the testing period. The shock elicits burying behavior by the rat. Following the first shock, the duration of time the rat spends spraying bedding material toward or over the probe with its snout or fore paws (burying behavior) is measured as well as the number of contact-induced shocks the rat receives from the probe. Known anxiolytic drugs reduce the amount of burying behavior. In addition, an index of the rat's reactivity to each shock is scored on a 4 point scale. The total time spent immobile during the 15 min testing period is used as an index of general activity. The shock-probe burying test is described in D. Treit, 1985, supra. The results of this test will demonstrate Benzoazolylpiperazine Compounds that are useful for treating or preventing anxiety.
5.14. Example 14: In Vivo Assays for Prevention or Treatment of an Addictive Disorder The condition place preference test or drug self-administration test can be used to assess the ability of Benzoazolylpiperazine Compounds to attenuate the rewarding properties of known drugs of abuse.
The Condition Place Preference Test: The apparatus for the conditioned place preference test consists of two large compartments (45x45x30 cm) made of wood with a plexiglass front wall. These two large compartments are distinctly different. Doors at the back of each large compartment lead to a smaller box (36x18x20 cm) box made of wood, painted grey, with a ceiling of wire mesh. The two large compartments differ in terms of shading (white vs black), level of illumination (the plexiglass door of the white compartment is covered with aluminum foil except for a window of 7x7 cm), texture (the white compartment has a 3 cm thick floor board (40x40 cm) with nine equally spaced 5 cm diameter holes and the black has a wire mesh floor), and olfactory cues (saline in the white compartment and 1 mL of 10% acetic acid in the black compartment). On habituation and testing days, the doors to the small box remain open, giving the rat free access to both large compartments. The first session that a rat is placed in the apparatus is a habituation session and entrances to the smaller grey compartment remain open giving the rat free access to both large compartments. During habituation, rats generally show no preference for either compartment. Following habituation, rats are given 6 conditioning sessions. Rats are divided into 4 groups: carrier pre-treatment + carrier (control group), 2-Pyrimidinylpiperazine Compound pre-treatment + earner, carrier pre-treatment + morphine, 2-Pyrimidinylpiperazine Compound pre-treatment + morphine. During each conditioning session the rat is injected with one of the drug combinations and confined to one compartment for 30 min. On the following day, the rat receives a carrier + carrier treatment and is confined to the other large compartment. Each rat receives three conditioning sessions consisting of 3 drug combination-compartment and 3 carrier-compartment pairings. The order of injections and the drug/compartment pairings are counterbalanced within groups. On the test day, rats are injected prior to testing (30 min to 1 hour) with either morphine or carrier and the rat is placed in the apparatus, the doors to the grey compartment remain open and the rat is allowed to explore the entire apparatus for 20 min. The time spent in each compartment is recorded. Known drugs of abuse increase the time spent in the drug-paired compartment during the testing session. If the Benzoazolylpiperazine Compound blocks the acquisition of morphine conditioned place preference (reward), there will be no difference in time spent in each side in rats pre-treated with a Benzoazolylpiperazine Compound and the group will not be different from the group of rats that was given carrier + carrier in both compartments. Data will be analyzed as time spent in each compartment (drug combination-paired vs carrier- paired). Generally, the experiment is repeated with a minimum of 3 doses of a Benzoazolylpiperazine Compound.
The Drug Self- Admimstration Test: The apparatus for the drug self- administration test is a standard commercially available operant conditioning chamber. Before drug trials begin rats are trained to press a lever for a food reward. After stable lever pressing behavior is acquired, rats are tested for acquisition of lever pressing for drug reward. Rats are implanted with chronically indwelling jugular catheters for i.v. administration of compounds and are allowed to recover for 7 days before training begins. Experimental sessions are conducted daily for 5 days in 3 hour sessions. Rats are trained to self-administer a known drug of abuse, such as morphine. Rats are then presented with two levers, an "active" lever and an "inactive" lever. Pressing of the active lever results in drug infusion on a fixed ratio 1 (FRI) schedule (i.e., one lever press gives an infusion) followed by a 20 second time out period (signaled by illumination of a light above the levers). Pressing of the inactive lever results in infusion of excipient. Training continues until the total number of morphine infusions stabilizes to within ± 10% per session. Trained rats are then used to evaluate the effect of Benzoazolylpiperazine Compounds pre-treatment on drug self- administration. On test day, rats are pre-treated with a Benzoazolylpiperazine Compound or excipient and then are allowed to self-administer drug as usual. If the Benzoazolylpiperazine Compound blocks the rewarding effects of morphine, rats pre-treated with the Benzoazolylpiperazine Compound will show a lower rate of responding compared to their previous rate of responding and compared to excipient pre-treated rats. Data is analyzed as the change in number of drag infusions per testing session (number of infusions during test session - number of infusions during training session). The results will demonstrate Benzoazolylpiperazine Compounds are useful for treating or preventing an addictive disorder.
5.15. Example 15: Functional Assay for Characterizing mGluR 1 Antagonistic Properties Functional assays for the characterization of mGluR 1 antagonistic properties are well known in the art. For example, the following procedure can be used.
A CHO-rat mGluRl cell line is generated using cDNA encoding rat mGluRl receptor (M. Masu and S. Nakanishi, Nature 349: 760-765 (1991)). The cDNA encoding rat mGluRl receptor can be obtained from, e.g., Prof. S. Nakanishi (Kyoto, Japan). 40,000 CHO-rat mGluRl cells/well are plated into a Costar 3409, black, clear bottom, 96 well, tissue culture treated plate (commercially available from Fisher Scientific of Chicago, IL) and are incubated in Dulbecco's Modified Eagle's Medium (DMEM, pH 7.4) supplemented with glutamine, 10% FBS, 1% Pen/Strep, and 500 μg/mL Geneticin for about 12 h. The CHO-rat mGluRl cells are then washed and treated with Optimem medium (commercially available from Invitrogen, Carlsbad, CA) and incubated for a time period ranging from 1 to 4 hours prior to loading the cells with the dye Fluo-4 (commercially available from Molecular Probes hie, Eugene OR). After incubation, the cell plates are washed with loading buffer (127 mM NaCl, 5 mM KC1, 2 mM MgCi2, 700 μM, NaH2PO_ι, 2 mM CaCl2, 5 mMNaHC03, 8 mM HEPES, and 10 mM glucose, pH 7.4) and incubated with 3 μM Fluo-4 in 0.1 mL loading buffer for 90 min. The cells are then washed twice with 0.2 mL loading buffer, resuspended in 0.1 mL of loading buffer, and fransfened to a Fluorometric Imaging Plate Reader (FLIPR) (commercially available from Molecular Devices Corp., Sunnyvale, CA) for measurement of calcium mobilization flux in the presence of glutamate and in the presence or absence of a Benzoazolylpiperazine Compound. To measure calcium mobilization flux, fluoresence is monitored for about 15 s to establish a baseline and DMSO solutions containing various concentrations of a Benzoazolylpiperazine Compound ranging from about 50 μM to about 0.8 nM diluted in loading buffer (0.05 mL of a 4X dilution) are added to the cell plate and fluoresence is monitored for about 2 min. 0.05 mL of a 4X Glutamate solution (agonist) is then added to each well to provide a final glutamate concentration in each well of 10 μM and fluoresence is monitored for about 1 additional min. The final DMSO concentration in the assay is 1%. a each experiment fluoresence is momtored as a function of time and the data is analyzed using a non-linear regression to determine the IC50 value, ha each expereiment each data point is determined twice.
5.16 Example 16: Binding of Benzoazolylpiperazine Compounds to VRl
5 Methods for demonstrating a compound's ability to inhibit NR1 are well known to those skilled in the art, for example, those methods disclosed in U.S. Patent No. 6,239,267 to Duckworth et al; U.S. Patent No. 6,406,908 to Mchatyre et al; or U.S. Patent No. 6,335,180 to Julius et al. The results of this assay will demonstrate Benzoazolylpiperazine Compounds that bind to and modulate the activity of VRl.
10 Binding of Compound AAQ to NR1 : Assay Protocol
Human VRl cloning. Human spinal cord RΝA (commercially available from Clontech, Palo Alto, CA) was used. Reverse transcription was conducted on 1.0 μg total RΝA using Thermoscript Reverse Transcriptase (commercially available from Invitrogen, Carlsbad, CA) and oligo dT primers as detailed in its product description. Reverse 15 transcription reactions were incubated at 55°C for 1 h, heat-inactivated at 85°C for 5 min, and RΝase H-treated at 37°C for 20 min.
Human NR1 cDΝA sequence was obtained by comparison of the human genomic sequence, prior to annotation, to the published rat sequence. Intron sequences were removed and flanking exonic sequences were joined to generate the hypothetical human 20 cDΝA. Primers flanking the coding region of human VRl were designed as follows: forward primer, AAGATCTTCGCTGGTTGCACACTGGGCCACA; and reverse primer, GAAGATCTTCGGGGACAGTGACGGTTGGATGT.
PCR of NR1 was performed on one tenth of the reverse transcription reaction mixture using Expand Long Template Polymerase and Expand Buffer 2 in a final volume of 25 50 μL according to the manufacturer's instructions (Roche Applied Sciences, Indianapolis, IN). After denaturation at 94°C for 2 min PCR amplification was performed for 25 cycles at 94°C for 15 sec, 58°C for 30 sec, and 68°C for 3 min followed by a final incubation at 72°C for 7 min to complete the amplification. A PCR product of ~2.8 kb was gel-isolated using a 1.0% agarose, Tris- Acetate gel containing 1.6 μg/mL of crystal violet and purified with a S.N.A.P. UN-Free Gel Purification Kit (commercially available from Invitrogen). The VRl PCR product was cloned into the ρIΝD/V5-His-TOPO vector (commercially available from Invitrogen) according to the manufacturer's instructions. DNA preparations, restriction enzyme digestions, and preliminary DNA sequencing were performed according to standard protocols. Full-length sequencing confirmed the identity of the human NR1.
Generation of inducible cell lines. Unless noted otherwise, cell culture reagents were purchased from Life Technologies of Rockville, MD. HEK293-EcR cells expressing the ecdysone receptor (commercially available from Invitrogen) were cultured in Growth Medium (Dulbecco's Modified Eagles Medium containing 10% fetal bovine serum (commercially available from HYCLOΝE, Logan, UT), lx penicillin/streptomycin, lx glutamine, 1 mM sodium pyruvate and 400 μg/mL Zeocin (commercially available from avifrogen)). The NRl-pIΝD constructs were transfected into the HEK293-EcR cell line using Fugene transfection reagent (commercially available from Roche Applied Sciences, Basel, Switzerland). After 48 h, cells were fransfened to Selection Medium (Growth Medium containing 300 μg/mL G418 (commercially available from Invitrogen)). Approximately 3 weeks later individual Zeocin/G418 resistant colonies were isolated and expanded. To identify functional clones, multiple colonies were plated into 96-well plates and expression was induced for 48 h using Selection Medium supplemented with 5 μM ponasterone A ("PonA") (commercially available from Invitrogen). On the day of assay, cells were loaded with Fluo-4 (a calcium-sensitive dye that is commercially available from Molecular Probes, Eugene, OR) and CAP-mediated calcium influx was measured using a Fluorometric Imaging Plate Reader ("FLIPR") (commercially available from Molecular Devices Corp., Sunnyvale, CA) as described below. Functional clones were re-assayed, expanded, and cryopreserved. pH-Based Assay. Two days prior to performing this assay, cells were seeded on poly-D-lysine-coated 96-well clear-bottom black plates (commercially available from Becton-Dickinson) at 75,000 cells/well in growth media containing 5 μM PonA (commercially available from Invitrogen) to induce expression. On the day of the assay, the 5 plates were washed with 0.2 mL lx Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 1.6 mM CaCl2 and 20 mM HEPES, pH 7.4 ("wash buffer"), and loaded using 0.1 mL of wash buffer containing Fluo-4 (3 μM final concentration, commercially available from Molecular Probes). After 1 h, the cells were washed twice with 0.2 mL wash buffer and resuspended in 0.05 mL lx Hank's Balanced Salt
10 Solution (commercially available from Life Technologies) containing 3.5 mM CaCl2 and 10 mM Citrate, pH 7.4 ("assay buffer"). Plates were then fransfened to a FLIPR (commercially available from Molecular Devices) for assay. Compound AAQ was diluted in assay buffer, and 50 mL of the resultant solution were added to the cell plates and the solution monitored for two minutes. The final concentration of Compound AAQ ranged from about 50 pM to
15 about 3 μM. Agonist buffer (wash buffer titrated with IN HCl to provide a solution having a pH of 5.5 when mixed 1 : 1 with assay buffer) (0.1 mL) was then added to each well, and the plates were incubated for 1 additional min. Data were collected over the entire time course and analyzed using Excel and Graph Pad Prism. Compound AAQ when assayed according to this protocol had an IC50 of 261.8 ± 75.1 (n = 6).
20 Capsaicin-based Assay. Two days prior to performing this assay, cells were seeded in poly-D-lysine-coated 96-well clear-bottom black plates (50,000 cells/well) in growth media containing 5 μM PonA (commercially available from Invitrogen) to induce expression. On the day of the assay, the plates were washed with 0.2 mL lx Hank's Balanced Salt Solution (commercially available from Life Technologies) containing 1 mM CaCl2 and
25 20 mM HEPES, pH 7.4, and cells were loaded using 0.1 mL of wash buffer containing Fluo-4 (3 μM final). After one h, the cells were washed twice with 0.2 mL of wash buffer and resuspended in 0.1 mL of wash buffer. The plates were fransfened to a FLIPR (commercially available from Molecular Devices) for assay. 50 μL of Compound AAQ diluted with assay buffer were added to the cell plates and incubated for 2 min. The final concentration of Compound AAQ ranged from about 50 pM to about 3 μM. Human VRl was activated by the addition of 50 μL of capsaicin (400 nM), and the plates were incubated for an additional 3 min. Data were collected over the entire time course and analyzed using Excel and GraphPad Prism. Compound AAQ when assayed according to this protocol had an IC50 of 50.7 ± 14.7 (n - 3).
The results of the pH-based assay and the capsaicin-based assay demonstrate that Compound AAQ, an illustrative Benzoazolylpiperazine Compound, binds to and modulates the activity of human NR1 and, accordingly, is useful for freating or preventing pain, UI, an ulcer, IBD, or JJBS.
The present invention is not to be limited in scope by the specific embodiments disclosed in the examples which are intended as illustrations of a few aspects of the invention and any embodiments that are functionally equivalent are within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to fall within the scope of the appended claims.
A number of references have been cited, the entire disclosures of which are incorporated herein by reference.

Claims

What is claimed is:
1. A compound of formula:
Figure imgf000648_0001
(la) or a pharmaceutically acceptable salt thereof, wherein Aτι is
Figure imgf000648_0002
A is
Figure imgf000648_0003
R, is -CI, -Br, -I, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo);
each R2 is independently:
(a) "halo> -CN' "OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-Cι4)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C,0)cycloalkyl, -(C8-Cι4)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicyclohetero cycle, each of which is unsubstituted or substituted with one or more Rj groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(C,-C6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7,
-NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH2(halo), or -CH(halo)2; R8 and Rg are each independently -H,
Figure imgf000650_0001
-(C2-C6)alkenyl,
-(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2,
-CH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; m is 0 or 1 ; and x is 0 or 1.
2. The compound of claim 1, wherein Arj is a pyridyl group.
3. The compoxmd of claim 1, wherein x is 1 and A is -C(O)N(R4)-.
4. The compound of claim 1, wherein Arj is a pyridyl group, x is 1, and A is
-C(O)N(R4)-.
5. The compound of claim 1, wherein Ar! is a pyridyl group, x is 1, and A is -C(S)N(R4)-.
6. The compound of claim 1, wherein n or p is 0.
7. The compound of claim 1 , wherein n or p is 1.
8. The compound of claim 1, wherein x is 0.
9. The compound of claim 1, wherein Ax: is a pyrimidinyl group
10. The compound of claim 1 , wherein Ar! is a pyrimidinyl group, x is 1 , and A is -C(O)N(R4)-.
11. The compound of claim 1 , wherein Aτι is a pyrimidinyl group, x is 1 , and A is -C(S)N(R4)-.
12. The compound of claim 1, wherein: R, is -CH3, CF3; -CI, -Br, or -I; m is O; n or p is O; x is 1;
A is -C(O)-N(R4)-;
R4 is -H;
R8 is -H; and g is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or-F.
13. The compound of claim 12, wherein A j is a pyridyl group.
14. The compound of claim 13, wherein R, is -CH3 and Rn is -CI.
15. The compoimd of claim 13, wherein R! is -CH3 and Rg is -Br.
16. The compound of claim 13, wherein Rj is -CH3 and Rg is -F.
17. The compound of claim 13, wherein R! is -CI and Rg is -CI.
18. The compound of claim 13, wherein R1 is -CI and Rg is -Br.
19. The compound of claim 13, wherein R, is -CI and Rg is -CI.
20. The compound of claim 1, wherein: R, is -CH3, CF3j -Cl, -Br, or -I; m is 1 ;
R3 is -(CrC10)alkyl; n or p is 0; x is 1;
A is -C(O)-N(R4)-; R4 is -H;
R8 is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
21. The compound of claim 20, wherein R3 is -CH3.
22. The compound of claim 20, wherein the carbon to which R3 is attached is in the (R) configuration.
23. The compound of claim 20, wherein R3 is attached to a carbon atom adjacent to a nitrogen atom attached to the -C(O)-N(R4)-group.
24. The compound of claim 20, wherein Ar! is a pyridyl group.
25. The compound of claim 24, wherein Rj is -CH3 and R, is -CI.
26. The compound of claim 25, wherein the carbon to which R3 is attached is in the (R) configuration.
27. The compound of claim 24, wherein Rj is -CH3 and Rg is -Br.
28. The compound of claim 27, wherein the carbon to which R3 is attached is in the (R) configuration.
29. The compound of claim 24, wherein Rj is -CH3 and Rg is -F.
30. The compound of claim 29, wherein the carbon to which R3 is attached is in the (R) configuration.
31. The compound of claim 24, wherein Rλ is -CI and Rg is -CI.
32. The compoxmd of claim 31 , wherein the carbon to which R3 is attached is in the (R) configuration.
33. The compound of claim 24, wherein Rj is -CI and Rg is -Br.
34. The compound of claim 33, wherein the carbon to which R3 is attached is in the (R) configuration.
35. The compound of claim 24, wherein Ri is -CI and Rg is -CI.
36. The compound of claim 35, wherein the carbon to which R3 is attached is in the (R) configuration.
37. The compoxmd of claim 1, wherein m is 1 and the carbon to which R3 is attached is in the (R) configuration.
38. A compound of formula:
Figure imgf000654_0001
(lb) or a pharmaceutically acceptable salt thereof, wherein
Ax-, is
Figure imgf000654_0002
A is
Figure imgf000654_0003
Rj is -H, -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(C1-C,0)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3-
C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rs groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloaιkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more Rg groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is O or l; and x is 0 or 1.
39. The compound of claim 38, wherein x is 1 and A is -C(O)N(R4)-.
40. The compound of claim 38, wherein Arj is a pyrazinyl group.
41. The compound of claim 38, wherein Ar! is a pyridazinyl group.
42. The compound of claim 38, wherein Ar, is a thiazanyl group.
43. The compound of claim 38, wherein Ar, is a pyrazinyl group, x is 1, and A is -C(O)N(R4)-.
44. The compound of claim 38, wherein Axλ is a pyrazinyl group, x is 1, and A is -C(S)N(R4)-.
45. The compound of claim 38, wherein Ax, is a pyridazinyl group, x is 1, and A is -C(O)N(R4)-.
46. The compound of claim 38, wherein Ar! is a pyridazinyl group, x is 1, and A is
-C(S)N(R4)-.
47. The compound of claim 38, wherein Ax, is a thiazanyl group, x is 1, and A is -C(O)N(R4)-.
48. The compound of claim 38, wherein Ar, is a thiazanyl group, x is 1, and A is -C(S)N(R4)-.
49. The compound of claim 38, wherein p is 0.
50. The compound of claim 38, wherein p is 1.
51. The compound of claim 38, wherein x is 0.
52. The compound of claim 38, wherein: R, is -CH3, CF3; -CI, -Br, or -I; m is O; p is 0; x is 1;
A is -C(O)-N(R4)~;
R4 is -H; R8 is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or-F.
53. The compound of claim 52, wherein R, is -CH3 and Rg is -CI.
54. The compound of claim 52, wherein R, is -CH3 and Rg is -Br.
55. The compound of claim 52, wherein R! is -CH3 and Rg is -F.
56. The compound of claim 52, wherein Rj is -CI and Rg is -CI.
57. The compound of claim 52, wherein R, is -CI and Rg is -Br.
58. The compound of claim 52, wherein R, is -CI and Rg is -CI.
59. The compound of claim 38, wherein: Rj is -CH3, CF3> -CI, -Br, or -I; m is 1; R3 is -(C1-C10)alkyl; p is 0; x is 1;
A is -C(O)-N(R4)-;
R4 is -H; R8 is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or-F.
60. The compound of claim 59, wherein R3 is -CH3.
61. The compound of claim 59, wherein the carbon to which R3 is attached is in the (R) configuration.
62. The compound of claim 59, wherein R3 is attached to a carbon atom adjacent to a nifrogen atom attached to the -C(O)-N(R4)-group.
63. The compoxmd of claim 59, wherein R is -CH3 and Rg is -CI.
64. The compound of claim 63, wherein the carbon to which R3 is attached is in the (R) configuration.
65. The compound of claim 59, wherein Rλ is -CH3 and Rg is -Br.
66. The compound of claim 65, wherein the carbon to which R3 is attached is in the (R) configuration.
67. The compound of claim 59, wherein R, is -CH3 and Rg is -F.
68. The compound of claim 67, wherein the carbon to which R3 is attached is in the (R) configuration.
69. The compound of claim 59, wherein R, is -CI and Rg is -CI.
70. The compound of claim 69, wherein the carbon to which R3 is attached is in the (R) configuration.
71. The compound of claim 59, wherein R, is -CI and R§ is -Br.
72. The compound of claim 71, wherein the carbon to which R3 is attached is in the (R) configuration.
73. The compound of claim 59, wherein R, is -CI and Rg is -CI.
74. The compound of claim 73, wherein the carbon to which R3 is attached is in the (R) configuration.
75. The compound of claim 38, wherein m is 1 and the carbon to which R3 is attached is in the (R) configuration.
76. A compound of formula:
Figure imgf000660_0001
(Ha) or a pharmaceutically acceptable salt thereof, wherein Arj is
Figure imgf000660_0002
or R, is -CI, -Br, -I, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3,
-CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-Cι4)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C,0)cycloalkenyl,-(C8-
C14)bicycloalkenyl, -(C8-C,4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- memberedjbicycloheterocycle, each of which is unsubstituted or substituted with one or more R-5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rj groups; or
(c) -phenyl, -naphthyl, -(Cι4)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently
Figure imgf000661_0001
-(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2; R8 and Rg are each independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl,
-(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7;
R10 is -H or -(CrC4)alkyl; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; and m is 0 or 1.
77. The compound of claim 76, wherein Ar, is a pyridyl group.
78. The compound of claim 76, wherein Arj is a pyrimidinyl group.
79. The compound of claim 76, wherein Ax{ is a pyrazinyl group.
80. The compound of claim 76, wherein n or p is 0.
81. The compound of claim 76, wherein n or p is 1.
82. The compound of claim 76, wherein: R, is -CH3, CF3; -CI, -Br, or -I; m is 0; n or p is 0;
Rg is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
83. The compound of claim 82, wherein Ar, is a pyridyl group.
84. The compound of claim 76, wherein: R, is -CH3, CF3; -CI, -Br, or -I; m is 1;
R3 is -(CrC10)alkyl; n or p is 0;
R8 is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
85. The compound of claim 84, wherein R3 is -CH3.
86. The compound of claim 84, wherein the carbon to which R3 is attached is in the (R) configuration.
87. The compound of claim 76, wherein the carbon to which R3 is attached is in the (R) configuration.
88. A compound offormula:
Figure imgf000663_0001
(nb) or a pharmaceutically acceptable salt thereof, wherein Ar, is
Figure imgf000664_0001
A is
Figure imgf000664_0002
R! is -H, -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3,
-CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(C,-C6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C1o)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more Rj groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloallcyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8-
C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(Cj-C^cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3,
-CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and g are each independently -H, -(C1-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; R10 is -H or -(C,-C4)alkyl; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is 0 or 1 ; and x is 0 or 1.
89. The compound of claim 88, wherein Ar, is a pyridazinyl group.
90. The compound of claim 88, wherein Ar, is a thiazanyl group.
91. The compound of claim 88, wherein x is 1 and A is -C(O)N(R4)-.
92. The compound of claim 88, wherein Ar, is a pyridazinyl group, x is 1, and A is
-C(O)N(R4)-.
93. The compound of claim 88, wherein Ar, is a pyridazinyl group, x is 1, and A is -C(S)N(R4)-.
94. The compound of claim 88, wherein p is 0.
95. The compound of claim 88, wherein p is 1.
96. The compound of claim 88, wherein x is 0.
97. The compound of claim 88, wherein Ar, is a thiazanyl group.
98. The compound of claim 88, wherein Ar, is a thiazanyl group, x is 1, and A is -C(O)N(R4)-.
99. The compound of claim 88, wherein Ar, is a thiazanyl group, x is 1, and A is -C(S)N(R4)-.
100. The compound of claim 88, wherein:
R, is -CH3, CF3) -CI, -Br, or -I; m is 0; p is O; x is 1;
A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
101. The compound of claim 88, wherein:
R, is -CH3, CF3j -CI, -Br, or -I; m is 1;
R3 is -(CrC10)alkyl; p is O; x is 1;
A is -C(O)-N(R4)-; R4 is -H;
R8 is -H; and
Rg is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
102. The compound of claim 101, wherein R3 is -CH3.
103. The compound of claim 101, wherein the carbon to which R3 is attached is in the (R) configuration.
104. The compound of claim 101, wherein R3 is attached to a carbon atom adjacent to a nifrogen atom attached to the -C(O)-N(R4)-group.
105. The compound of claim 88, wherein m is 1 and the carbon to which R3 is attached is in the (R) configuration.
106. A compound of formula:
Figure imgf000668_0001
(UXa) or a pharmaceutically acceptable salt thereof, wherein
Ar, is
Figure imgf000668_0002
A is
Figure imgf000668_0003
R, is -CI, -Br, -I, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2; (b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7,
-NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(Cj-C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; m is 0 or 1 ; and x is O or l.
107. The compound of claim 106, wherein Ar, is a pyridyl group.
108. The compound of claim 106, wherein x is 1 and A is -C(O)N(R4)-.
109. The compound of claim 106, wherein Ar! is a pyridyl group, x is 1, and A is -C(O)N(R4)-.
110. The compound of claim 106, wherein Ar, is a pyridyl group, x is 1, and A is -C(S)N(R4)-.
111. The compound of claim 106, wherein n or p is 0.
112. The compound of claim 106, wherein n or p is 1.
113. The compound of claim 106, wherein x is 0.
114. The compound of claim 106, wherein Ax, is a pyrimidinyl group
115. The compound of claim 106, wherein Arj is a pyrimidinyl group, x is 1 , and A N(R4)-.
116. The compound of claim 106, wherein Axλ is a pyrimidinyl group, x is 1, and A N(R4)-.
117. The compound of claim 106, wherein: R, is -CH3, CF3> -CI, -Br, or -I; m is 0; n or p is 0; x is 1;
A is -C(O)-N(R4)-; R4 is -H;
R8 is -H; and
R9 is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or-F.
118. The compound of claim 106, wherein: R, is -CH3, CF3> -CI, -Br, or -I; m is 1;
R3 is -(CrC10)alkyl; n or p is 0; x is 1; A is -C(O)-N(R4)-;
R4 is -H; R8 is -H; and R9 is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
119. The compound of claim 118, wherein R3 is -CH3.
120. The compound of claim 118, wherein the carbon to which R3 is attached is in the (R) configuration.
121. The compound of claim 118, wherein R3 is attached to a carbon atom adjacent to a nifrogen atom attached to the -C(O)-N(R )-group.
122. The compound of claim 106, wherein m is 1 and the carbon to which R3 is attached is in the (R) configuration.
123. A compound of formula:
Figure imgf000672_0001
or a pharmaceutically acceptable salt thereof, wherein Ar, is
Figure imgf000673_0001
A is
Figure imgf000673_0002
R, is -H, -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(C1-C10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C,4)tricycloalkyl, -(C5-C,0)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, or -(7- to 10-membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, or-(C14)aryl each of which is unsubstituted or substituted with one or more R6 groups; each R3 is independently: (a) -halo, -CN, -OH, -O(CrC6)alkyl, -NO2, or -NH2;
(b) -(CrC10)alkyl, -(C2-C10)alkenyl, -(C2-C10)alkynyl, -(C3- C10)cycloalkyl, -(C8-C14)bicycloalkyl, -(C8-C14)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C14)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or (c) -phenyl, -naphthyl, -(C14)aryl or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R4 is -H or -(CrC6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7,
-NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(Cs-C^cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -( -C^alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(Cj-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; p is an integer ranging from 0 to 2; m is 0 or 1 ; and x is 0 or 1.
124. The compound of claim 123, wherein Ar! is a pyrazinyl group.
125. The compound of claim 123, wherein x is 1 and A is -C(O)N(R4)-.
126. The compound of claim 123, wherein Ar, is a pyrazinyl group, x is 1, and A is -C(O)N(R4)-.
127. The compound of claim 123, wherein Ar, is a pyrazinyl group, x is 1 , and A is -C(S)N(R4)-.
128. The compound of claim 123, wherein p is 0.
129. The compound of claim 123, wherein p is 1.
130. The compound of claim 123, wherein x is 0.
131. The compound of claim 123, wherein Ar, is a pyridazinyl group
132. The compound of claim 123, wherein Ar, is a pyridazinyl group, x is 1, and A is -C(O)N(R4)-.
133. The compound of claim 123, wherein Ar, is a pyridazinyl group, x is 1, and A is -C(S)N(R4)-.
134. The compound of claim 123, wherein Ar, is a thiazanyl group.
135. The compound of claim 123, wherein Ar, is a thiazanyl group, x is 1, and A is -C(O)N(R4)-.
136. The compound of claim 123, wherein Ar, is a thiazanyl group, x is 1, and A is
-C(S)N(R4)-.
137. The compound of claim 123, wherein: R, is -CH3, CF3j -CI, -Br, or -I; m is O; p is 0; x is 1;
A is -C(O)-N(R4)-; R4 is -H; R8 is -H; and R9 is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
138. The compound of claim 123, wherein: R, is -CH3, CF3; -CI, -Br, or -I; m is 1;
R3 is -(C,-C,0)alkyl; p is O; x is 1;
A is -C(O)-N(R4)-;
R4 is -H;
R8 is -H; and R9 is -CH3, CF3, -OCH2CH3, tert-butyl, CI, -Br-, or -F.
139. The compound of claim 138, wherein R3 is -CH3.
140. The compound of claim 138, wherein the carbon to which R3 is attached is in the (R) configuration.
141. The compound of claim 138, wherein R3 is attached to a carbon atom adjacent to a nitrogen atom attached to the -C(O)-N(R4)-group.
142. The compound of claim 123, wherein m is 1 and the carbon to which R3 is attached is in the (R) configuration.
143. A composition comprising the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123 and a pharmaceutically acceptable vehicle.
144. A method for treating or preventing pain in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
145. A method for treating or preventing urinary incontinence in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
146. A method for treating or preventing an ulcer in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
147. A method for treating or preventing irritable-bowel syndrome in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
148. A method for treating or preventing inflammatory-bowel disease in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
149. A method for treating or preventing an addictive disorder in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
150. A method for treating or preventing Parkinson's disease in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
151. A method for treating or preventing parkinsonism in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
152. A method for treating or preventing anxiety in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
153. A method for treating or preventing epilepsy in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
154. A method for treating or preventing stroke in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
155. A method for treating or preventing a seizure in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
156. A method for treating or preventing a pruritic condition in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
157. A method for treating or preventing psychosis in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
158. A method for treating or preventing a cognitive disorder in an animal, comprising administering to an animal in need thereof an effective amount of the compoxmd or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
159. A method for treating or preventing a memory deficit in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
160. A method for treating or preventing restricted brain function in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
161. A method for treating or preventing Huntington' s chorea in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
162. A method for treating or preventing amyofrophic lateral sclerosis in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
163. A method for treating or preventing retinopathy in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
164. A method for treating or preventing a muscle spasm in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
165. A method for treating or preventing a migraine in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
166. A method for treating or preventing vomiting in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
167. A method for treating or preventing dyskinesia in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
168. A method for treating or preventing depression in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
169. A method for inhibiting NR1 function in a cell comprising contacting a cell capable of expressing NR1 with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
170. A method for inhibiting n GluR5 function in a cell comprising contacting a cell capable of expressing mGluR5 with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
171. A method for inhibiting mGluRl function in a cell comprising contacting a cell capable of expressing mGluRl with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
172. A kit comprising a container containing an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123.
173. A method for preparing a composition comprising the step of admixing a compound or a pharmaceutically acceptable salt of the compound of any one of claims 1, 38, 76, 88, 106, or 123 and a phannaceutically acceptable vehicle.
174. A compound selected from the group consisting of
Figure imgf000683_0001
Figure imgf000683_0002
Figure imgf000684_0001
Figure imgf000684_0002
and pharmaceutically acceptable salts thereof.
175. A compound selected from the group consisting of
Figure imgf000685_0001
Figure imgf000685_0002
Figure imgf000686_0001
Figure imgf000686_0002
and pharmaceutically acceptable salts thereof.
176. A compound selected from the group consisting of
Figure imgf000687_0001
and pharmaceutically acceptable salts thereof.
177. A compound of formula:
Figure imgf000687_0002
(IVa) or a pharmaceutically acceptable salt thereof, wherein
Ar, is
Figure imgf000688_0001
Ar2 is
Figure imgf000688_0002
R, is -halo, -(C,-C6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(C,-C6)alkyl, -NO2, or -NH2;
(b) -(C,-C,0)alkyl, -(C2-C,0)alkenyl, -(C2-C,0)alkynyl, -(C3- Cιo)cycloalkyl, -(C8-C,4)bicycloalkyl, -(C8-Ci4)tricycloalkyl, -(C5-C,0)cycloalkenyl,-(C8- C,4)bicycloalkenyl, -(C8-C14)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or
(c) -phenyl, -naphthyl, -(C,4)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups; R3 is -H or -CH3: each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2;
R8 and Rg are each independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; and p is an integer ranging from 0 to 2.
178. A compound of formula:
Figure imgf000689_0001
(IVb) or a pharmaceutically acceptable salt thereof, wherein Ar, is
Figure imgf000690_0001
Ar2 is
Figure imgf000690_0002
A is
Figure imgf000690_0003
R, is -halo, -(CrC6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(C,-C6)alkyl, -NO2, or -NH2;
(b) -(C,-C,0)alkyl, -(C2-C,0)alkenyl, -(C2-C,0)alkynyl, -(C3- C,0)cycloalkyl, -(C8-C,4)bicycloalkyl, -(C8-C,4)tricycloalkyl, -(C5-C,0)cycloalkenyl,-(C8- C,4)bicycloalkenyl, -(C8-C,4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or (c) -phenyl, -naphthyl, -(C,4)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R3 is -CH3; R4 is -H or -(C,-C6)alkyl; each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2; R8 and Rg are each independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl,
-(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; p is an integer ranging from 0 to 2; and x is 0 or 1.
179. A composition comprising the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178 and a pharmaceutically acceptable vehicle.
180. A method for treating or preventing pain in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
181. A method for treating or preventing urinary incontinence in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
182. A method for freating or preventing an ulcer in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
183. A method for freating or preventing irritable-bowel syndrome in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
184. A method for treating or preventing inflammatory-bowel disease in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
185. A method for treating or preventing an addictive disorder in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
186. A method for treating or preventing Parkinson's disease in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
187. A method for treating or preventing parkinsonism in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
188. A method for treating or preventing anxiety in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
189. A method for treating or preventing epilepsy in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
190. A method for treating or preventing stroke in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
191. A method for freating or preventing a seizure in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
192. A method for treating or preventing a pruritic condition in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
193. A method for treating or preventing psychosis in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
194. A method for treating or preventing a cognitive disorder in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
195. A method for freating or preventing a memory deficit in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
196. A method for treating or preventing restricted brain function in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
197. A method for freating or preventing Huntington's chorea in an animal, comprising admimstering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
198. A method for treating or preventing amyotrophic lateral sclerosis in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
199. A method for treating or preventing retinopathy in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
200. A method for treating or preventing a muscle spasm in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
201. A method for treating or preventing a migraine in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
202. A method for treating or preventing vomiting in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
203. A method for treating or preventing dyskinesia in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
204. A method for treating or preventing depression in an animal, comprising administering to an animal in need thereof an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
205. A method for inhibiting VRl function in a cell comprising contacting a cell capable of expressing NRl with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
206. A method for inhibiting mGluR5 function in a cell comprising contacting a cell capable of expressing mGluR5 with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
207. A method for inhibiting mGluRl function in a cell comprising contacting a cell capable of expressing mGluRl with an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
208. A kit comprising a container containing an effective amount of the compound or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178.
209. A method for preparing a composition comprising the step of admixing a compoxmd or a pharmaceutically acceptable salt of the compound of any one of claims 177 or 178 and a pharmaceutically acceptable vehicle.
210. A composition comprising:
(i) an effective amount of a compound offormula:
Figure imgf000696_0001
(V) or a pharmaceutically acceptable salt thereof, wherein Ar, is
Figure imgf000696_0002
Ar2 is
Figure imgf000697_0001
R, is -halo, -(C,-C6)alkyl, -NO2, -CN, -OH, -OCH3, -NH2, -C(halo)3, -CH(halo)2, or -CH2(halo); each R2 is independently:
(a) -halo, -CN, -OH, -O(C,-C6)alkyl, -NO2, or -NH2; (b) -(C,-C10)alkyl, -(C2-C,0)alkenyl, -(C2-C,0)alkynyl, -(C3-
C,0)cycloalkyl, -(C8-C,4)bicycloalkyl, -(C8-C,4)tricycloalkyl, -(C5-C10)cycloalkenyl,-(C8- C,4)bicycloalkenyl, -(C8-C,4)tricycloalkenyl, -(3- to 7-membered)heterocycle, or -(7- to 10- membered)bicycloheterocycle, each of which is unsubstituted or substituted with one or more R5 groups; or (c) -phenyl, -naphthyl, -(C,4)aryl, or -(5- to 10- membered)heteroaryl, each of which is unsubstituted or substituted with one or more R6 groups;
R3 is -H or -CH3: each R5 is independently -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R6 is independently -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -OH, -halo, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each R7 is independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl,
-(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C3-C5)heterocycle, -C(halo)3, -CH2(halo), or -CH(halo)2; R8 and Rg are each independently -H, -(C,-C6)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3-C8)cycloalkyl, -(C3-C8)cycloalkenyl, -phenyl, -C(halo)3, -CH(halo)2, -CH2(halo), -OC(halo)3, -OCH(halo)2, -OCH2(halo), -CN, -OH, -halo, -N3, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -COR7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7, or -S(O)2R7; each -halo is -F, -CI, -Br,- or -I; n is an integer ranging from 0 to 3; and p is an integer ranging from 0 to 2; and (ii) a pharmaceutically acceptable carrier or excipient..
211. A method for treating or preventing pain in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
212. A method for freating or preventing urinary incontinence in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
213. A method for treating or preventing an ulcer in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
214. A method for treating or preventing irritable-bowel syndrome in an animal, comprising admimstering to an animal in need thereof an effective amount of the composition of claim 210.
215. A method for freating or preventing inflammatory-bowel disease in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
5 216. A method for freating or preventing an addictive disorder in an animal, comprising administering to an animal in need thereof an effective amoxmt of the composition of claim 210.
217. A method for treating or preventing Parkinson's disease in an animal,
10 comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
218. A method for treating or preventing parkinsonism in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim
15 210.
219. A method for freating or preventing anxiety in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
20
220. A method for freating or preventing epilepsy in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
25 221. A method for treating or preventing stroke in an animal, comprising administering to an animal in need thereof an effective amoxmt of the composition of claim 210.
222. A method for treating or preventing a seizure in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
223. A method for freating or preventing a pruritic condition in an animal, comprising admimstering to an animal in need thereof an effective amoxmt of the composition of claim 210.
224. A method for treating or preventing psychosis in an animal, comprising admimstering to an animal in need thereof an effective amoxmt of the composition of claim 210.
225. A method for freating or preventing a cognitive disorder in an animal, comprising admimstering to an animal in need thereof an effective amount of the composition of claim 210.
226. A method for treating or preventing a memory deficit in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
227. A method for freating or preventing restricted brain function in an animal, comprising administering to an animal in need thereof an effective amoxmt of the composition of claim 210.
228. A method for freating or preventing Huntington's chorea in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
229. A method for treating or preventing amyotrophic lateral sclerosis in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
5 230. A method for treating or preventing retinopathy in an animal, comprising admimstering to an animal in need thereof an effective amount of the composition of claim 210.
231. A method for treating or preventing a muscle spasm in an animal, comprising 10 administering to an animal in need thereof an effective amount of the composition of claim
210.
232. A method for treating or preventing a migraine in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim
15 210.
233. A method for treating or preventing vomiting in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210. 0
234. A method for treating or preventing dyskinesia in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
5 235. A method for treating or preventing depression in an animal, comprising administering to an animal in need thereof an effective amount of the composition of claim 210.
236. A method for inhibiting NRl function in a cell comprising contacting a cell capable of expressing NRl with an effective amount of the composition of claim 210.
237. A method for inhibiting mGluR5 function in a cell comprising contacting a cell capable of expressing mGluR5 with an effective amoxmt of the composition of claim 210.
238. A method for inhibiting mGluRl function in a cell comprising contacting a cell capable of expressing mGluRl with an effective amount of the composition of claim 210.
239. A kit comprising a container containing an effective amount of the composition of claim 210.
PCT/US2003/041100 2002-12-24 2003-12-22 Benzoazolypiperazine derivatives having mglur1- and mglur5-antagonistic activity WO2004058754A1 (en)

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AU2003297506A AU2003297506A1 (en) 2002-12-24 2003-12-22 Benzoazolylpiperazine derivatives having VR1antagonist activity
SI200331239T SI1583763T1 (en) 2002-12-24 2003-12-22 Benzoazolylpiperazine derivatives having vr1-antagonist activity
DE60320033T DE60320033T2 (en) 2002-12-24 2003-12-22 BENZOAZOLYLPIPERAZINE DERIVATIVES WITH VR1 ANTAGONISTIC EFFECT
JP2005510054A JP4680774B2 (en) 2002-12-24 2003-12-22 Benzazolylpiperazine derivatives with antagonist activity
BR0317757-2A BR0317757A (en) 2002-12-24 2003-12-22 Compound, composition, methods for treating or preventing pain, urinary incontinence, an ulcer, syndrome, irritable bowel, inflammatory bowel disease, an addict disorder, parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, an epileptic seizure , a pruritically condition, psychosis, a cognitive impairment, a memory deficit, restricted brain function, huntington's chorea, amyotrophic lateral sclerosis, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia and depression in an animal to inhibit vr1 function. , mglur5 and mglur1 in a cell, kit, and method for preparing a composition
MXPA05006869A MXPA05006869A (en) 2002-12-24 2003-12-22 Benzoazolypiperazine derivatives having mglur1- and mglur5-antagonistic activity.
EA200501022A EA200501022A1 (en) 2002-12-24 2003-12-22 DERIVATIVES OF BENZOAZOLYLIPIPERAZINE WITH ANTAGONIST VR1 ACTIVITY
NZ541415A NZ541415A (en) 2002-12-24 2003-12-22 Benzoazolylpiperazine derivatives having metabotropic glutamate receptor 1 and receptor 5 (mGluR1- and mGluR5-) antagonistic activity
CA2511509A CA2511509C (en) 2002-12-24 2003-12-22 Benzoazolylpiperazine derivatives having vr1 antagonist activity
YUP-2005/0498A RS20050498A (en) 2002-12-24 2003-12-22 Benzoazolypiperazine derivatives having vr1 antagonistic activity
DK03814351T DK1583763T3 (en) 2002-12-24 2003-12-22 Benzoazolylpiperazine derivatives with VR1 antagonist activity
EP03814351A EP1583763B1 (en) 2002-12-24 2003-12-22 Benzoazolylpiperazine derivatives having vr1-antagonist activity
IL169378A IL169378A0 (en) 2002-12-24 2005-06-23 Benzoazolypiperazine derivatives having vr1 antagonistic activity
NO20053582A NO20053582L (en) 2002-12-24 2005-07-22 Benzoazolylpiperazine derivatives having VRI antagonist activity.
HR20050666A HRP20050666B1 (en) 2002-12-24 2005-07-22 Benzoazolylpiperazine derivatives having vr1 antagonist activity
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