CN101130526B - Aryl carbonyl derivatives as therapeutic agents - Google Patents

Abstract

This invention relates to aryl carbonyl derivatives of the general formula (I), which are activators of glucokinase which may be useful for the management, treatment, control, or adjunct treatment of diseases, where increasing glucokinase activity is beneficial.(Formul 1).

Description

Aryl carbonyl derivatives as therapeutical agent

The application be that June 27, application number in 2003 are 03820170.4 the applying date, denomination of invention divides an application for the Chinese patent application of " as the aryl carbonyl derivatives of therapeutical agent ".

Invention field

The present invention relates to compound, they are activator of glucokinase (GK), can be used for management, treatment, control or the assisting therapy of disease, and it is useful wherein increasing the glucokinase activity.

Background of invention

Diabetes are feature with the glucose metabolism impairment, show as blood glucose levels rising etc. in the diabetic subject.According to this defective, diabetes are divided into two kinds of main types: type 1 diabetes, perhaps insulin requirements type diabetes (IDDM), when lacking the beta cell that produces Regular Insulin, patient's pancreas occurs, and diabetes B, perhaps non insulin dependent diabetes (NIDDM), this occur in that the beta cell function lowers and some other unusual patients in.

Type 1 diabetes is insulinize at present, and most of diabetes B be with the sulfonylurea that stimulates the beta cell function or with the enhancing patient to the medicine of the structure sensitive properties of Regular Insulin or insulinize.Be used for strengthening tissue to the medicine of insulin sensitivity, metformin is a representative example.

Even sulfonylurea is widely used in the treatment of NIDDM, but this therapy is not gratifying in most occasion: in a large amount of NIDDM patients, the sulfonylurea deficiency is so that glucose level normalizing, and therefore the patient faces the very high-risk of suffering from diabetic complication.And a lot of patients lose the ability in response to sulfonylurea treatment gradually, thereby are forced to accept insulinize gradually.The transformation of patient from oral antidiabetic drug to insulin treatment is usually owing to the depletion of beta cell the NIDDM patient.

In normal individual and diabetic individual, liver produces glucose for fear of hypoglycemia.This glucose produces and comes from release or the glyconeogenesis of glucose from the glycogen deposit, and the latter is synthesizing in capitulum of glucose.But in diabetes B, some is out of control in the adjusting of hepatic glucose output, increases in the back of spending the night on an empty stomach, and may double.And, in these patients, between the increase of fasting plasma glucose level and hepatic glucose generation speed, there is strong mutual relationship.Equally, hepatic glucose produces will be increased in type 1 diabetes to some extent, if this disease is not subjected to the appropriate control of insulinize.

Because existing diabetotherapy form can not cause sufficient glycemic control, be not satisfied therefore, there is huge demand in the methods for the treatment of of novelty.

Atherosclerosis is a kind of disease of artery, is acknowledged as dead leading reason in the U.S. and West Europe.Cause that the cardiopathic pathology of atherosclerosis and occlusive know in proper order.The commitment of this order is to form " fatty streak " in carotid artery, coronary artery and cerebral arteries and aorta.Because the existence of lipid deposits, these damages are yellow colors, are mainly seen in the smooth muscle cell and in the scavenger cell of artery and aortic tunica intima layer.And then, infer that great majority see the formation that cholesterol in the fatty streak cause " fibrous plaque " then, form by the fully loaded lipid of accumulating and by extracellular lipid, intimal smooth muscle cells that collagen, elastin and proteoglycan surrounded.Cell adds matrix and constitutes fibrous cap, covers darker cell debris settling and more extracellular lipid.Lipid mainly is that dissociate and cholesterol esterification.Fibrous plaque slowly forms, might in time become calcification with necrosis, make progress and be " concurrent damage ", caused the trend of thrombosis and artery muscle spasm on arterial occlusion and the wall, these are that late arterial is atherosis peculiar.

The epidemiology evidence has been defined as hyperlipemia to be caused by atherosclerosis the primary hazard factor of cardiovascular disorder (CVD).In recent years, medical expert drums in, and reducing blood plasma cholesterol level, particularly low density lipoprotein cholesterol is the steps necessary of CVD prevention.The upper limit of " normally " now known significantly be lower than be familiar with before this.Therefore, recognize that now most of westerner faces extra high danger.Independently Hazard Factor comprise glucose intolerance, left ventricular hypertrophy, hypertension and male gender.Cardiovascular disorder is especially general in diabetic individual, and at least part of reason is to have multiple independent hazard factor in this group people.In common people, particularly in diabetic individual, therefore successful hyperlipemia treatment seems especially important.

Hypertension is a kind of like this illness, and it is as the secondary symptom of various other obstacles and take place in the crowd, for example renal artery stenosis, pheochromocytoma or endocrine disorder.But, hypertension also has in the patient of a lot of causes of disease or obstacle the unknown and manifests.Although this class " special send out property " hypertension is often with relevant with hypertriglyceridemia such as obesity, diabetes, but the relation between these obstacles is not illustrated as yet.In addition, a lot of patients show hypertensive symptom in the presence of fully without any other diseases or obstacle sign.

Known hypertension can directly cause heart failure, renal failure and apoplexy (hematencephalon).These illnesss can cause patient's short-term death.Hypertension also can promote the development of atherosclerosis and coronary artery disease.These illnesss make patient's weakness gradually, can cause long-term death.

The definite reason of essential hypertension and unclear, but a large amount of factor it is believed that and helps the initial of this disease.Salt and the water excess that this class factor has anxiety, loses one's temper, hormone discharges imbalance (feritin, Angiotensin aldosterone system), caused by the kidney dysfunction, cause vasoconstrictive vascular system wall thickening and hypertrophy and inherited genetic factors.

Essential hypertension has been considered above-mentioned factor when taking to treat.Thereby developed and gone on the market widely beta-Blocking agent, vasoconstrictor, angiotensin-convertion enzyme inhibitor etc. as antihypertensive drug.Adopt verified being of value to of hypertension therapeutic of these compounds to prevent short-term death, for example heart failure, renal failure and hematencephalon.But, atherosclerosis or the heart trouble that is caused by long-term hypertension forms the problem that remains.Although this has hinted that hypertension has been lowered, but the immanent cause of essential hypertension does not produce reaction to this treatment.

Hypertension is relevant with the rising of blood insulin level, and this illness is called as hyperinsulinemia.Regular Insulin is a kind of peptide hormone, and its main effect is to promote the generation of glucose utilization, protein synthesis and neutral lipid and storage etc., especially also plays the effect that promotes vascular cell growth and increase the kidney sodium retention.These functions described later not affecting glucose level can realize, are known hypertension reasons.The peripheral vasculature growth for example can cause the periphery kapillary to shrink, and the sodium retention meeting increases blood volume.Thereby the insulin level that reduces the hyperinsulinemia patient can prevent the abnormal vascular growth and the kidney sodium retention that are caused by high insulin levels, thus alleviating hypertension.

Megalocardia is the important risk factor during sudden death, myocardial infarction and congestive heart failure form.These cardiac events are owing to local asphyxia and after the perfusion myocardial damage susceptibility are increased that in the part degree these can occur in the out-patient and perform the operation the recent stage at least.Medically also can't prevent or reduce the recent consequence of disadvantageous cardiac muscle operation, the recent myocardial infarction of particularly performing the operation.Non-heart is all relevant with the substantive danger of myocardial infarction or death with heart operation.Have 7,000,000 patients that accept non-cardiac surgery to be considered to adventurous, the incidence of the recent death of performing the operation in some cases and serious cardiac complication is up to 20-25%.In addition, accept in every year among 400,000 patients of coronary artery by-pass operation, the recent myocardial infarction of performing the operation incidence according to estimates is 5%, and mortality ratio is 1-2%.Do not have at present pharmacotherapy to can be used for reducing the recent myocardial ischemia of operation to the infringement of heart tissue in this respect or strengthen heart to the tolerance of ischemic episode.But a kind of like this therapy expection prolongs life reduces hospital care, improves the quality of life of high-risk patient and reduces the general health nursing cost.

Obesity is the Hazard Factor that a lot of common diseases known form, for example atherosclerosis, hypertension and diabetes.Fat and these disease incidence rate are all increasing in the whole industrialization world.Except exercise, diet and food restriction, do not exist the compellent pharmacological treatment can be effectively and reduce body weight acceptably at present.But, since as a kind of Hazard Factor in fatal and common disorder indirectly and significant effects finds that fat treatment and/or the means of appetite stimulator will be important.

The term obesity has hinted the excess fat tissue.In this article, the fat obesity that preferably is counted as any degree, it brings danger for health.Boundary between the normal and obese individuals can only be about, but the health risk that is brought by obesity is likely the continuity that obesity increases progressively.Framingham studies have shown that, surpasses ideal body weight 20% and obviously can bring danger (Mann GV N.Engl.J.Med 291:226,1974) for health.In the U.S., the fat panel discussion group approval of NationalInstitutes of Health with regard to the young adult, relative weight increase by 20% or weight index (BMI=body weight kilogram number divided by height rice number square) 85% or more health is being constituted danger.Utilize these standards, it is fat (NIH, Ann Intern Med 103:147,1985) that there are 20-30% adult man and 30-40 adult female in the U.S..

Even slight obesity has also increased and has early died young, the danger of diabetes, hypertension, atherosclerosis, gallbladder disease and some types of cancer.In industrialized the Western countries, fat ubiquity significantly increases between many decades in the past.In view of the high ubiquity of obesity and it to health affected, its prevention and treatment should be that public health institute is top-priority.

What when energy intake surpass to consume, too much heat was stored in the fatty tissue, if this clean positive sexual balance continues, just causeed fat, and that is to say that the body weight balance has two kinds of components, any (picked-up or consume) can both cause obesity unusually.

The understanding that the feed behavior is regulated is still incomplete.Appetite is subjected to the control in each zone of hypothalamus to a certain extent: the satiety maincenter in the feeding center in the hypothalamus ventral lateral nucleus of thalamus (VLH) and the ventromedial hypothalamus VMH (VMH).Brain cortex receives the positivity signal from feeding center, stimulates feed, and the satiety maincenter is regulated and control this process by sending suppressor pulse to feeding center.Some regulate processes all may influence these hypothalamic cellses.The satiety maincenter can activate because of plasma glucose and/or Regular Insulin increase after meal.The gastric dilatation that meals bring out is another kind of possible inhibition factor.In addition, hypothalamic cells is responsive to catecholamine, and the beta-adrenergic hormesis suppresses the feed behavior.Finally, brain cortex control feed behavior, the pulse from feeding center to brain cortex is once to import only.Psychology, society and inherited genetic factors also influence ingestion of food.

At present, multiple technologies can be used for realizing preliminary losing weight.Unfortunately, tentatively losing weight not is best therapeutic goal.On the contrary, problem is most of obese patients weightening finishes again at last.The effective means of setting up and/or continuing to lose weight is the huge challenge in Bariatric today.

The WO 00/58293 of Hoffman-La Roche, WO 01/44216, WO 01/83465, WO 01/83478, WO 01/85706, WO 01/85707 and WO 02/08209 disclose the compound as glucokinase activating agents.

Summary of the invention

The invention provides the amide derivatives of general formula (I), as described below, they are activator of glucokinase.The compounds of this invention can be used as glucokinase activating agents, thereby can be used for wherein increasing the glucokinase activity and can be benefited.This class disease comprises type i diabetes and type ii diabetes.The invention provides compound as described below, the pharmaceutical composition that comprises these compounds, they are for increasing the purposes of glucokinase activity, their purposes in the medication preparation of the described disease for the treatment of and illness, the purposes of the described disease of The compounds of this invention or medicine composite for curing and illness, and the method for the treatment of described disease and illness, these methods comprise to the curee that these needs are arranged give significant quantity according to compound of the present invention.

The present invention also provides glucokinase activating agents, general formula (I) compound for example, and they are glucose-sensitive glucokinase activating agents, such glucokinase activating agents just, their activity increases and reduces along with glucose concn.

The present invention also provides glucokinase activating agents, general formula (I) compound for example, they are liver-specificity glucokinase activating agents, such glucokinase activating agents just, they can increase the glucose utilization (just increasing glycogen deposition) in the liver, and do not induce insulin secretion in response to glucose any increase to be arranged.

The invention provides the purposes that is used for the treatment of metabolic disturbance according to compound of the present invention or pharmaceutical preparations.

The invention provides according to compound of the present invention or the pharmaceutical preparations purposes for reducing blood-glucose.

The invention provides the purposes that is used for the prevention hyperglycemia according to compound of the present invention or pharmaceutical preparations.

The invention provides according to compound of the present invention or pharmaceutical preparations and be used for the treatment of glucose tolerance impaired (impaired glucose tolerance, purposes IGT).

The invention provides the purposes that is used for the treatment of X syndrome according to compound of the present invention or pharmaceutical preparations.

The invention provides according to compound of the present invention or pharmaceutical preparations and be used for the treatment of fasting glucose attenuating (impaired fasting glucose, purposes IFG).

The invention provides the purposes that is used for the treatment of diabetes B according to compound of the present invention or pharmaceutical preparations.

The invention provides the purposes that is used for the treatment of type 1 diabetes according to compound of the present invention or pharmaceutical preparations.

The invention provides according to compound of the present invention or pharmaceutical preparations and be the purposes of diabetes B for delay glucose tolerance impaired (IGT) progress.

The invention provides according to compound of the present invention or pharmaceutical preparations and be the purposes of insulin requirements type diabetes B for delaying non-insulin demand type diabetes B progress.

The invention provides the purposes that is used for the treatment of hyperlipemia or hyperlipemia according to compound of the present invention or pharmaceutical preparations.

The invention provides according to compound of the present invention or pharmaceutical preparations and be used for the treatment of hypertensive purposes.

The invention provides according to compound of the present invention or pharmaceutical preparations and be used for the treatment of fat purposes.

The invention provides according to compound of the present invention or the pharmaceutical preparations purposes for reducing ingestion of food.

The invention provides according to compound of the present invention or pharmaceutical preparations and be used for purposes at appetite stimulator.

The invention provides the purposes that is used for regulating feeding behavior according to compound of the present invention or pharmaceutical preparations.

The invention provides the purposes that is used for strengthening incretin (enteroincretin), for example GLP-1 secretion according to compound of the present invention or pharmaceutical preparations.

The invention provides the purposes that is used for the assisting therapy type 1 diabetes, takes place with the prevent diabetes complication according to compound of the present invention or pharmaceutical preparations.

The invention provides according to compound of the present invention or the pharmaceutical preparations purposes for increasing β cell quantity in the mammalian subject and/or size.

The invention provides the apoptotic purposes that is used for the treatment of β cytopathy, particularly β cell according to compound of the present invention or pharmaceutical preparations.

The invention provides the purposes that is used for the treatment of functional dyspepsia, particularly irritable bowel syndrome according to compound of the present invention or pharmaceutical preparations.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of metabolic disturbance.

The invention provides compound according to the present invention for the preparation of the purposes for reducing the medicine of blood-glucose.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of hyperglycemia.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of IGT.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of X syndrome.

The invention provides compound according to the present invention lowers the medicine of (IFG) for the preparation of the treatment fasting glucose purposes.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of diabetes B.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of type 1 diabetes.

The invention provides compound according to the present invention for the preparation of the purposes of delay glucose tolerance impaired (IGT) progress for the medicine of diabetes B.

The invention provides compound according to the present invention for the preparation of delaying the purposes of non-insulin demand type diabetes B progress for the medicine of insulin requirements type diabetes B.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of hyperlipemia.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of hyperlipemia.

The invention provides compound according to the present invention for the preparation of the purposes of the hypertensive medicine for the treatment of.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine that reduces ingestion of food.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine that is used for appetite stimulator.

The invention provides compound according to the present invention for the preparation of the purposes of the fat medicine for the treatment of.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine of regulating feeding behavior.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine that strengthens incretin, for example GLP-1 secretion.

The invention provides the purposes of the medicine that compound according to the present invention takes place for the preparation of the assisting therapy type 1 diabetes, with the prevent diabetes complication.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine of β cell quantity and/or size in the increase mammalian subject.

The invention provides compound according to the present invention for the preparation for the treatment of β cytopathy, the particularly purposes of the apoptotic medicine of β cell.

The invention provides compound according to the present invention for the preparation of the purposes of the medicine for the treatment of functional dyspepsia, particularly irritable bowel syndrome.

The invention provides the hypoglycemic method of prevention, comprise the administration of liver-specificity glucokinase activating agents.

The invention provides liver-specificity glucokinase activating agents for the preparation of the purposes of the hypoglycemic medicine of prevention.

Other embodiments and aspect are as hereinafter defined with claims.

Definition

The structural formula neutralization that provides at this paper spreads all in this specification sheets, and following term has following meanings.

Term used herein " optional substituted " means that relevant group is unsubstituted or is replaced by one or more specified substituting groups.When relevant group was replaced by an above substituting group, this substituting group can be identical or different.

Term used herein " adjacent " is related to the relative position of two atoms or variable, these two atoms or variable share a key or variable in variable mode before or after another.For instance, " the A atom is adjacent to the B atom " means that two atom A and B share a key.

Term " halogen " or " halo " expression fluorine, chlorine, bromine or iodine.

Term " perhalogeno methyl " expression trifluoromethyl, trichloromethyl, trisbromomethyl or three iodomethyls.

The prefix designates shown type atomic group of following array structure has x to y carbon atom: C _X-y-alkyl, C _X-y-thiazolinyl, C _X-y-alkynyl, C _X-y-cyclic hydrocarbon radical or C _X-y-cycloalkyl-C _X-y-thiazolinyl.

Term used herein " alkyl " separately or unite the saturated monovalence hydrocarbon of the straight or branched atomic group that expression has one to ten carbon atom, for example C _1-8-alkyl or C _1-6-alkyl.Typical C _1-8-alkyl and C _1-6-alkyl for example includes but not limited to methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, 2-methyl butyl, 3-methyl butyl, 4-methyl amyl, neo-pentyl, n-pentyl, n-hexyl, 1,2-dimethyl propyl, 2,2-dimethyl propyl, 1,2,2-trimethylammonium propyl group etc.Term " C used herein _1-8-alkyl " also comprise C _3-8-secondary alkyl and C _4-8-tertiary alkyl.Term " C used herein _1-6-alkyl " also comprise C _3-6-secondary alkyl and C _4-6-tertiary alkyl.

Term used herein " alkylidene group " separately or unite the saturated divalence hydrocarbon of the straight or branched atomic group that expression has one to ten carbon atom, for example C _1-8-alkylidene group or C _1-6-alkylidene group.The example of " alkylidene group " used herein includes but not limited to methylene radical, ethylidene etc.

Term used herein " thiazolinyl " separately or unite the straight or branched monovalence hydrocarbon atomic group that expression contains two to ten carbon atoms and at least one carbon-to-carbon double bond, for example C _2-8-thiazolinyl or C _2-6-thiazolinyl.Typical C _2-8-thiazolinyl and C _2-6-thiazolinyl includes but not limited to vinyl, 1-propenyl, 2-propenyl, pseudoallyl, 1,3-butadienyl, 1-butylene base, crotyl, 3-butenyl, 2-methyl isophthalic acid-propenyl, 1-pentenyl, pentenyl, 3-pentenyl, 4-pentenyl, 3-methyl-2-butene base, 1-hexenyl, 2-hexenyl, 3-hexenyl, 2,4-hexadienyl, 5-hexenyl etc.

Term used herein " alkenylene " separately or unite the straight or branched divalence hydrocarbon atomic group that expression has two to ten carbon atoms and at least one carbon-to-carbon double bond, for example C _2-8-alkenylene or C _2-6-alkenylene.Typical C _2-8-alkenylene and C _2-6-alkenylene includes but not limited to ethene-1,2-two bases, propylene-1, and 3-two bases, methylene-1,1-two bases (methylenne-1,1-diyl) etc.

Term used herein " alkynyl " separately or unite the straight or branched monovalence hydrocarbon atomic group that expression contains two to ten carbon atoms and at least one carbon-to-carbon, three key, for example C _2-8-alkynyl or C _2-6-alkynyl.Typical C _2-8-alkynyl and C _2-6-alkynyl includes but not limited to ethynyl, 1-proyl, 2-propynyl, ethyl acetylene base, 2-butyne base, 3-butynyl, 1-pentynyl, valerylene base, 3-pentynyl, 4-pentynyl, 1-hexin base, 2-hexin base, 3-hexin base, 5-hexin base, 2,4-hexadiyne base etc.

Term used herein " alkynylene " separately or unite the straight or branched divalence hydrocarbon atomic group that expression has two to ten carbon atoms and at least one carbon-to-carbon, three key, for example C _2-8-alkynylene or C _2-6-alkynylene.Typical C _2-8-alkynylene and C _2-6-alkynylene includes but not limited to acetylene-1,2-two bases, propine-1,3-two bases etc.

Term used herein " cyclic hydrocarbon radical " separately or unite the non-aromatic monovalence hydrocarbon atomic group that expression has three to 12 carbon atoms and optional one or more degrees of unsaturation, for example C _3-8-cyclic hydrocarbon radical.A kind of like this ring can condense with one or more phenyl ring or one or more other cyclic hydrocarbon basic rings alternatively.Typical C _3-8-cyclic hydrocarbon radical includes but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, suberane base, cycloheptenyl, ring octyl group etc.

Term used herein " inferior cyclic hydrocarbon radical " separately or unite expression and have three to 12 carbon atoms and the non-aromatic carbocyclic ring divalence hydrocarbon atomic group of one or more degrees of unsaturation, for example C alternatively _3-8-Ya cyclic hydrocarbon radical.A kind of like this ring can condense with one or more phenyl ring or one or more other cyclic hydrocarbon basic rings alternatively.Typical C _3-8-Ya cyclic hydrocarbon radical includes but not limited to cyclopropyl-1,1-two bases, cyclopropyl-1,2-two bases, cyclobutyl-1,2-two bases, cyclopentyl-1,3-two bases, cyclohexyl-1,4-two bases, suberane base-1,4-two bases or ring octyl group-1,5-two bases etc.

Term used herein " heterocycle " or term " heterocyclic radical " are independent or unite three to the ten binary heterocycles that expression has one or more degrees of unsaturation, wherein contain one or more S of being selected from, SO, SO ₂, O or N hetero atom substituents, C for example _3-8-heterocyclic radical.A kind of like this ring can be alternatively condenses with ring or the cyclic hydrocarbon basic ring of one or more another " heterocycles ".Typical C _3-8-heterocyclic radical includes but not limited to tetrahydrofuran (THF), 1,4-two _ alkane, 1,3-two _ alkane, piperidines, tetramethyleneimine, morpholine, piperazine etc.

Term used herein " inferior heterocyclic radical " is independent or unite optional three to the ten binary heterocycle bivalent atom groups with one or more degrees of unsaturation of expression, wherein contains one or more S of being selected from, SO, SO ₂, O or N heteroatoms.A kind of like this ring can be alternatively condenses with ring or the cyclic hydrocarbon basic ring of one or more phenyl ring or one or more another " heterocycles ".The example of " inferior heterocyclic radical " includes but not limited to tetrahydrofuran (THF)-2,5-two bases, morpholine-2,3-two bases, pyrans-2,4-two bases, 1,4-two _ alkane-2,3-two bases, 1,3-two _ alkane-2,4-two bases, piperidines-2,4-two bases, piperidines-1,4-two bases, tetramethyleneimine-1,3-two bases, morpholine-2,4-two bases, piperazine-1,4-two bases etc.

Term used herein " alkoxyl group " separately or unite expression monovalent radical R ^aO-, wherein R ^aBe alkyl, for example C as defined above _1-8-alkyl obtains C _1-8-alkoxyl group.Typical C _1-8-alkoxyl group includes but not limited to methoxyl group, oxyethyl group, positive propoxy, isopropoxy, butoxy, sec-butoxy, tert.-butoxy, pentyloxy, isopentyloxy, hexyloxy, different hexyloxy etc.

Term used herein " alkylthio " is independent or unite expression straight or branched monovalent radical, wherein comprises aforesaid alkyl, connects by bivalent sulfur atom, and its free valence bond is from this sulphur atom, for example C _1-8-alkylthio.Typical C _1-8-alkylthio includes but not limited to methylthio group, ethylmercapto group, rosickyite base, butylthio, penta sulfenyl, own sulfenyl etc.

Term used herein " alkoxy carbonyl " expression monovalent radical R ^aOC (O)-, R wherein ^aBe aforesaid alkyl, for example C _1-8-alkoxy carbonyl.Typical C _1-8-alkoxy carbonyl includes but not limited to methoxycarbonyl, ethoxycarbonyl, the third oxygen carbonyl, isopropyl oxygen carbonyl, positive butoxy carbonyl, secondary butoxy carbonyl, tertbutyloxycarbonyl, 3-methyl butoxy carbonyl, just own oxygen carbonyl etc.

Term used herein " carbamyl " expression NH ₂C (O)-.

Term used herein " aryl " expression carbocyclic aromatic annular atoms group or aromatics ring system atomic group.Aryl also is intended to comprise the partial hydrogenation derivative of carbon-loop system.

Term used herein " heteroaryl " separately or unite expression aromatic ring atomic group, for example have 5 to 7 yuan of atoms, perhaps represent aromatics ring system atomic group, for example have 7 to 18 yuan of atoms, contain one or more heteroatomss that are selected from nitrogen, oxygen or sulfur heteroatom, wherein N-oxide compound and sulphur monoxide and sulphur dioxide also are that admissible heteroaromatic replaces; For example furyl, thienyl, thiophenyl, pyrryl, imidazolyl, pyrazolyl, triazolyl, tetrazyl, thiazolyl, _ the azoles base, different _ the azoles base, _ di azoly, thiadiazolyl group, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl (benzothiophenyl), indyl and indazolyl etc.Heteroaryl also plans to comprise the partial hydrogenation derivative of the following heterocyclic ring system of enumerating.

The example of " aryl " and " heteroaryl " includes but not limited to phenyl, biphenyl, indenes, fluorenes, naphthyl (1-naphthyl, the 2-naphthyl), anthracene (1-anthryl, the 2-anthryl, the 3-anthryl), thiophene (2-thienyl, the 3-thienyl), furyl (2-furyl, the 3-furyl), indyl, _ di azoly, different _ the azoles base, thiadiazolyl group, _ triazolyl, the thiatriazole base, quinazoline, fluorenyl, xanthenyl, different dihydro indenyl, diphenyl-methyl, acridyl, thiazolyl, pyrryl (1-pyrryl, the 2-pyrryl, the 3-pyrryl), pyrazolyl (1-pyrazolyl, the 3-pyrazolyl, the 4-pyrazolyl, the 5-pyrazolyl), imidazolyl (1-imidazolyl, the 2-imidazolyl, the 4-imidazolyl, the 5-imidazolyl), triazolyl (1,2, the 3-triazol-1-yl, 1,2,3-triazole-4-base, 1,2,3-triazole-5-base, 1,2,4-triazole-3-base, 1,2,4-triazole-5-yl), _ azoles base (2-_ azoles base, 4-_ azoles base, 5-_ azoles base), different _ the azoles base (different _ azoles-the 3-base, different _ azoles-the 4-base, different _ azoles-the 5-yl), isothiazolyl (isothiazole-3-base, isothiazole-4-base, isothiazole-5-yl), thiazolyl (2-thiazolyl, the 4-thiazolyl, the 5-thiazolyl), pyridyl (2-pyridyl, the 3-pyridyl, the 4-pyridyl), pyrimidyl (2-pyrimidyl, the 4-pyrimidyl, the 5-pyrimidyl, the 6-pyrimidyl), pyrazinyl, pyridazinyl (3-pyridazinyl, the 4-pyridazinyl, the 5-pyridazinyl), quinolyl (2-quinolyl, the 3-quinolyl, the 4-quinolyl, the 5-quinolyl, the 6-quinolyl, the 7-quinolyl, the 8-quinolyl), isoquinolyl (1-isoquinolyl, the 3-isoquinolyl, the 4-isoquinolyl, the 5-isoquinolyl, the 6-isoquinolyl, the 7-isoquinolyl, the 8-isoquinolyl), benzo [b] furyl (2-benzo [b] furyl, 3-benzo [b] furyl, 4-benzo [b] furyl, 5-benzo [b] furyl, 6-benzo [b] furyl, 7-benzo [b] furyl), 2, (2-(2 for 3-dihydro-benzo [b] furyl, 3-dihydro-benzo [b] furyl), 3-(2,3-dihydro-benzo [b] furyl), 4-(2,3-dihydro-benzo [b] furyl), 5-(2,3-dihydro-benzo [b] furyl), 6-(2,3-dihydro-benzo [b] furyl), 7-(2,3-dihydro-benzo [b] furyl)), benzo [b] thienyl (benzo [b] thiophene-2-base, benzo [b] thiene-3-yl-, benzo [b] thiophene-4-base, benzo [b] thiophene-5-base, benzo [b] thiophene-6-base, benzo [b] thiophene-7-yl), 2,3-dihydro-benzo [b] thienyl (2,3-dihydro-benzo [b] thiophene-2-base, 2,3-dihydro-benzo [b] thiene-3-yl-, 2,3-dihydro-benzo [b] thiophene-4-base, 2,3-dihydro-benzo [b] thiophene-5-base, 2,3-dihydro-benzo [b] thiophene-6-base, 2,3-dihydro-benzo [b] thiophene-7-yl), indyl (1-indyl, the 2-indyl, the 3-indyl, the 4-indyl, the 5-indyl, the 6-indyl, the 7-indyl), indazole (1-indazolyl, the 3-indazolyl, the 4-indazolyl, the 5-indazolyl, the 6-indazolyl, the 7-indazolyl), benzimidazolyl-(1-benzimidazolyl-, the 2-benzimidazolyl-, the 4-benzimidazolyl-, the 5-benzimidazolyl-, the 6-benzimidazolyl-, the 7-benzimidazolyl-, the 8-benzimidazolyl-), benzo _ azoles base (2-benzo _ azoles base, 3-benzo _ azoles base, 4-benzo _ azoles base, 5-benzo _ azoles base, 6-benzo _ azoles base, 7-benzo _ azoles base), benzothiazolyl (2-[4-morpholinodithio base, the 4-benzothiazolyl, the 5-benzothiazolyl, the 6-benzothiazolyl, the 7-benzothiazolyl), carbazyl (1-carbazyl, the 2-carbazyl, the 3-carbazyl, the 4-carbazyl), 5H-dibenzo [b, f] azepine _ (5H-dibenzo [b, f] azepine _-the 1-base, 5H-dibenzo [b, f] azepine _-the 2-base, 5H-dibenzo [b, f] azepine _-the 3-base, 5H-dibenzo [b, f] azepine _-the 4-base, 5H-dibenzo [b, f] azepine _-the 5-yl), 10,11-dihydro-5H-dibenzo [b, f] azepine _ (10,11-dihydro-5H-dibenzo [b, f] azepine _-the 1-base, 10,11-dihydro-5H-dibenzo [b, f] azepine _-the 2-base, 10,11-dihydro-5H-dibenzo [b, f] azepine _-the 3-base, 10,11-dihydro-5H-dibenzo [b, f] azepine _-the 4-base, 10,11-dihydro-5H-dibenzo [b, f] azepine _-the 5-yl), benzo [1,3] dioxole (2-benzo [1,3] dioxole, 4-benzo [1,3] dioxole, 5-benzo [1,3] dioxole, 6-benzo [1,3] dioxole, 7-benzo [1,3] dioxole), purine radicals and tetrazyl (5-tetrazyl, the N-tetrazyl).

The present invention also relates to the partially or completely saturated analogue of above-mentioned ring system.

When two these class terms are united when using, for example aryl-alkyl-, heteroaryl-alkyl-, cyclic hydrocarbon radical-C _1-6-alkyl etc., the substituting group on this atomic group that is understood that to mention after the atomic group of mentioning earlier is replaces point and is positioned on latter's atomic group, for example

Aryl-alkyl-:

Cyclic hydrocarbon radical-alkyl-:

With

Aryl-alkoxyl group-:

Term used herein " arylidene " separately or unite expression carbocyclic aromatic ring bivalent atom group or aromatics ring system bivalent atom group.The example of " arylidene " includes but not limited to benzene-1,4-two bases, naphthalene-1,8-two bases etc.Term " arylidene " separately or unite other bivalent atom groups of the monovalent radical of mentioning in the definition that is also included within aryl.

Term used herein " inferior heteroaryl " separately or unite five to seven yuan of aromatic ring bivalent atoms groups of expression or aromatics ring system bivalent atom group, contain one or more heteroatomss that are selected from nitrogen, oxygen or sulfur heteroatom, wherein N-oxide compound and sulphur monoxide and sulphur dioxide also are that admissible heteroaromatic replaces.The example of " inferior heteroaryl " used herein has furans-2,5-two bases, thiophene-2,4-two bases, 1,3,4-_ diazole-2,5-two bases, 1,3,4-thiadiazoles-2,5-two bases, 1,3-thiazole-2,4-two bases, 1,3-thiazoles-2,5-two bases, pyridine-2,4-two bases, pyridine-2,3-two bases, pyridine-2,5-two bases, pyrimidine-2,4-two bases, quinoline-2,3-two bases etc.Term " inferior heteroaryl " separately or unite other bivalent atom groups of the monovalent radical of mentioning in the definition that is also included within heteroaryl.

Term used herein " the cyclic hydrocarbon radical aryl that condenses " expression and aryl-fused cyclic hydrocarbon radical, the two enjoys two atoms jointly, and wherein this aryl is to replace point.The example of " the cyclic hydrocarbon radical aryl that condenses " used herein comprises 5-dihydro indenyl, 5,6,7,8-tetrahydrochysene-2-naphthyl,

Deng.

The cyclic hydrocarbon radical aryl that term used herein " the cyclic hydrocarbon radical arylidene that condenses " expression condenses, wherein this aryl is divalence.Example comprises

Deng.

The aryl that term used herein " the aryl rings alkyl that condenses " expression and cyclic hydrocarbon radical condense, the two enjoys two atoms jointly, and wherein this cyclic hydrocarbon radical is to replace point.The example of " the aryl rings alkyl that condenses " used herein comprise 1-dihydro indenyl, 2-dihydro indenyl, 1-(1,2,3,4-tetralyl),

Deng.

Term used herein " the inferior cyclic hydrocarbon radical of the aryl that condenses " the aryl rings alkyl that expression condenses, wherein this cyclic hydrocarbon radical is divalence.Example comprises

Deng.

Term used herein " condensed heterocycle Ji Fangji " expression and aryl-fused heterocyclic radical, the two enjoys two atoms jointly, and wherein this aryl is to replace point.The example of " condensed heterocycle Ji Fangji " used herein comprise 3,4-methylene-dioxy-1-phenyl,

Deng.

Term used herein " condensed heterocycle base arylidene " expression condensed heterocycle Ji Fangji, wherein this aryl is divalence.Example comprises

Deng.

The aryl that term used herein " the aryl-heterocyclic base that condenses " expression and heterocyclic radical condense, the two enjoys two atoms jointly, and wherein this heterocyclic radical is to replace point.The example of " the aryl-heterocyclic base that condenses " used herein comprise 2-(1,3-benzodioxole base),

Deng.

Term used herein " the inferior heterocyclic radical of the aryl that condenses " the aryl-heterocyclic base that expression condenses, wherein this heterocyclic radical is divalence.Example comprises

Deng.

Term used herein " the cyclic hydrocarbon radical heteroaryl that condenses " represents and heteroaryl-condensed cyclic hydrocarbon radical that the two enjoys two atoms jointly, and wherein this heteroaryl is to replace point.The example of " the cyclic hydrocarbon radical heteroaryl that condenses " used herein comprise 5-azepine-6-dihydro indenyl,

4,5,6,7-tetrahydrochysene-benzothiazole-2-base,

5,6-dihydro-4-H-cyclopenta thiazol-2-yl (5,6-dihydro-4-H-cyclopentatiazole-2-yl),

Deng.

Term used herein " the inferior cyclic hydrocarbon radical of the heteroaryl that condenses " the heteroaryl ring alkyl that expression condenses, wherein this cyclic hydrocarbon radical is divalence.Example comprises

Deng.

Term used herein " condensed heterocycle base heteroaryl " represents and heteroaryl-condensed heterocyclic radical that the two enjoys two atoms jointly, and wherein this heteroaryl is to replace point.The example of " condensed heterocycle base heteroaryl " used herein comprise 1,2,3,4-tetrahydrochysene-β-Ka Lin-8-base,

Deng.

Term used herein " condensed heterocycle base inferior heteroaryl " expression condensed heterocycle base heteroaryl, wherein this heteroaryl is divalence.Example comprises

Deng.

The heteroaryl that term used herein " the heteroaryl heterocyclic radical that condenses " expression and heterocyclic radical condense, the two enjoys two atoms jointly, and wherein this heterocyclic radical is to replace point.The example of " the heteroaryl heterocyclic radical that condenses " used herein comprises 5-azepine-2,3-Dihydrobenzofuranes-2-base,

Deng.

Term used herein " the inferior heterocyclic radical of the heteroaryl that condenses " the heteroaryl heterocyclic radical that expression condenses, wherein this heterocyclic radical is divalence.Example comprises

Deng.

Term used herein " alkylthio " expression radicals R ^aS-, wherein R ^aIt is aforesaid alkyl.

Term used herein " alkyl sulphinyl " expression radicals R ^aS (O)-, R wherein ^aIt is aforesaid alkyl.

Term used herein " alkyl sulphonyl " expression radicals R ^aSO ₂-, R wherein ^aIt is aforesaid alkyl.

Term used herein " acyl group " expression radicals R ^aC (O)-, R wherein ^aBe aforesaid alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical, cycloalkenyl group or heterocyclic radical.

Term used herein " aroyl " expression radicals R ^aC (O)-, R wherein ^aIt is aforesaid aryl.

Term used herein " 4-hetaroylpyrazol " expression radicals R ^aC (O)-, R wherein ^aIt is aforesaid heteroaryl.

Term used herein " aryloxycarbonyl " expression radicals R ^a-O-C (O)-, R wherein ^aIt is aforesaid aryl.

Term used herein " acyloxy " expression radicals R ^aC (O) O-, wherein R ^aBe aforesaid alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical, cycloalkenyl group or heterocyclic radical.

Term used herein " aryloxy " expression radicals R ^a-O-, wherein R ^aIt is aforesaid aryl.

Term used herein " aryl acyloxy " expression radicals R ^aC (O) O-, wherein R ^aIt is aforesaid aryl.

Term used herein " assorted aryl acyloxy " expression radicals R ^aC (O) O-, wherein R ^aIt is aforesaid heteroaryl.

When no matter when term " alkyl ", " cyclic hydrocarbon radical ", " aryl ", " heteroaryl " etc. or their prefix root appeared in the title of substituting group (for example alkoxy aryl aryloxy), they all should be interpreted as comprising as above about those given restrictions of " alkyl " and " aryl ".

Substituting group=O should be represented in term used herein " oxo ".

Substituting group-SH should be represented in term used herein " sulfydryl ".

Substituting group-COOH should be represented in term used herein " carboxyl ".

Substituting group-CN should be represented in term used herein " cyano group ".

Substituting group-SO should be represented in term used herein " amino-sulfonyl " ₂NH ₂

Substituting group-S-should be represented in term used herein " sulfenyl ".

Term used herein " sulfinyl " should represent substituting group-S (O)-.

Substituting group-S (O) should be represented in term used herein " alkylsulfonyl " ₂-.

Term used herein " directly key " is if the part of structure variable explanation then represents to be regarded as the substituent direct connection in variable side (front and back) of " directly key ".

Term used herein " rudimentary " expression has any group of one to six carbon, can use prefix C _X-6-expression.Low alkyl group thereby can be expressed as C _1-6-alkyl, and low-grade alkylidene can be expressed as C _2-6-alkylidene group.

Such as C _X-y-cyclic hydrocarbon radical-C _A-bAtomic groups such as-thiazolinyl should show that the tie point of this atomic group is the part of last-mentioned atomic group.

Term used herein " alternatively " means that described event can take place also can not take place subsequently, comprises event and not event.

Term used herein " replacement " expression is replaced by specified substituting group, and a plurality of substitution values also allow, and other has except the stipulator.

Term used herein " contains " can represent that alkyl, thiazolinyl, alkynyl or cyclic hydrocarbon radical are at an arbitrary position by one or more any O, S, SO, SO as defined above ₂, N or the online replacement of N-alkyl, for example comprise-CH ₂-O-CH ₂-,-CH ₂-SO ₂-CH ₂-,-CH ₂-NH-CH ₃Deng.

Some is more than term can occur once in structural formula as defined above, in case occur repeatedly, then each term all should be defined independently of one another.

Term used herein " solvate " is the variable mixture of stoichiometry that is generated by solute (in the present invention, being formula (I) compound) and solvent.Can not disturb the biologic activity of solute for this kind solvent of the object of the invention.Solvent for example can be water, ethanol or acetic acid.

Term used herein " biological hydrolyzable ester " be drug substance (in the present invention, be formula (I) compound) ester, it a) can not disturb the biological activity of parent material, but give this material with character in the favourable body, for example acting duration, effect begin etc., perhaps b) lifeless matter activity, but be converted into bioactive ingredients by the curee easily in vivo.Its advantage for example be biological hydrolyzable ester by oral from intestinal absorption, in blood plasma, be converted into (I).Known in the art have a lot of these class examples, for example comprises lower alkyl esters (C for example _1-4), low-grade acyloxy alkyl ester, lower alkoxy acyloxy alkyl ester, alkoxyl group acyloxyate, alkyl amido alkyl ester and cholinesterase.

Term used herein " biological hydrolyzable acid amides " be drug substance (in the present invention, be general formula (I) compound) acid amides, it a) can not disturb the biological activity of parent material, but give this material with character in the favourable body, for example acting duration, effect begin etc., perhaps b) lifeless matter activity, but be converted into bioactive ingredients by the curee easily in vivo.Its advantage for example be biological hydrolyzable acid amides by oral from intestinal absorption, in blood plasma, be converted into (I).Known in the art have a lot of these class examples, for example comprises low alkyl group acid amides, alpha-amino acid amides, alkoxyl group acyl group acid amides and alkylamino alkyl-carbonyl acid amides.

Term used herein " prodrug " comprises biological hydrolyzable acid amides and biological hydrolyzable ester, also contain a) such compound, wherein the biological hydrolyzable functionality in a kind of like this prodrug is encompassed in formula (I) compound, and b) such compound, they can obtain the drug substance of formula (I) by bio-oxidation or reduction in given functional group.The example of these functional groups includes but not limited to 1,4-dihydropyridine, N-alkyl-carbonyl-1,4-dihydropyridine, 1, the tertiary butyl etc.

Term " on the pharmacology effectively amount " should represent that medicine or pharmaceutical agent will cause the biology looked for by researchist or clinicist in tissue, the animal or human's class or the amount of medicinal response.This amount can be effectively to measure on the therapeutics.Term " is effectively measured on the therapeutics " and should be represented that medicine or pharmaceutical agent will cause the amount of the treatment response of looking in animal or human's class.

Term used herein " treatment " is represented for the purpose of antagonism disease, obstacle or illness patient's management and nursing.The broad-spectrum curing with regard to the patient suffers from given obstacle planned to comprise in this term, for example delay disease, obstacle or illness progress, alleviate or relax symptom and complication, preventing disease and/or healing or eliminate a disease, obstacle or illness.The patient who treats is Mammals preferably, and is particularly human.

The Regular Insulin that the Regular Insulin of the natural generation of term used herein " insulin human " expression or reorganization produce.The recombinant human insulin can produce in the host cell that is fit to arbitrarily, and for example host cell can be bacterium, fungi (comprising yeast), insect, animal or plant cell.

Phraseology used herein " insulin derivates " (with relevant phraseology) expression insulin human or its analogue, wherein at least one organic substituent is bonded on one or more amino acid.

The such insulin human of " human insulin analogue " used herein (with relevant phraseology) expression, wherein one or more amino acid have lacked and/or have been replaced by other amino acid (comprise can not amino acids coding), perhaps such insulin human, it comprises other amino acid, just more than 51 amino acid, so that the gained analogue possesses insulin activity.

Detailed description of the invention

Glucokinase (GK) is played an important role in the blood-glucose homeostasis.The phosphorylation of GK catalysis glucose is the rate-limiting reaction of glycolysis in liver cell and the pancreas beta cell.In liver, GK determines glucose uptake and the synthetic speed of glycogen, and it also is regarded as adjusting necessary (Girard, J.et al., the Annu RevNutr of various glucose-responsive genes 17, 325-352 (1997)).In beta cell, GK determines the utilization of glucose, thereby is that the insulin secretion of glucose-stimulation is necessary.GK is also being expressed among the hypothalamus neurons group (it may participate in feeding behavior at this) and in intestines (it may help the secretion of incretin at this).

GK has two kinds of different principal characters: its expression, need to only limit to the tissue (being mainly liver and pancreas beta cell) of glucose-perceptibility, and it is to the S0.5 of glucose, and this is much higher than other members of (8-12mM) hexokinase family.Because these dynamic characteristics, the variation of serum level of glucose is parallel to the variation of glucose metabolism in the liver, and the latter regulates the balance between hepatic glucose output and the glucose consumption then.

The activator of glucokinase thereby can be used for the treatment of and wherein increase the more useful disease of glucokinase specific activity.Thereby, there is demand for the medicine that activates glucokinase and increase glucokinase enzymatic activity.This class medicine will can be used for treating type i diabetes and type ii diabetes.

The activator of glucokinase also can produce figure in the neurohumour response in perception low dextrose level with to hypoglycemia, thereby can be used for the treatment of the patient who suffers from type 1 diabetes, and they have the hypoglycemic trend of higher trouble.

Type i diabetes is a kind of disease of complexity, is feature with blood glucose concentration rising and diuresis.Be secondary to the lasting rising of blood-glucose, the patient develops into crushing complication, for example retinopathy, ephrosis, neuropathy and cardiovascular disorder.The major objective of improving the diabetes phenotype is to reduce on an empty stomach and post-prandial hyperglycemia, thereby avoids or the generation of delaying complications of diabetes.DCCT shows, by every day repeatedly injection of insulin carry out close glycemic control, can delay the generation of complication.But, this class reinforcement therapy is higher relevant with the danger that develops into the hypoglycemia event with weight increase.Therefore the replacement therapy of realizing glucose control and not having these side effects is untapped.The overexpression of GK in liver provides in the type 1 diabetes animal than the better glycemic control effect of single insulinize (Morral, N., et al.Human GeneTherapy with being combined in of subcutaneous injection of insulin 13, 1561-1570 (2002)).And the overexpression of liver GK can be in the compensation of part degree by the formed metabolic disturbance of insulin receptor-deficient mice (Jackerott, M.et al.Diabetologia 45, 1292-1297 (2002)).

The present invention also relates to the purposes of GK activator in diabetes and fat combination therapy.GK, GK regulate albumen and the KATP passage is expressed in hypothalamic neurone, and this brain district plays an important role in the control of regulation of energy and ingestion of food.Shown that these neuron expressions promote appetite and the neuropeptide that lowers appetite, be assumed that the glucose-perceptibility neurone in the hypothalamus, they are subjected to the inhibition of environment glucose concn variation or excite (Mobbs, C.V.et al, American Journal of Physiology, Endocrinology ﹠amp; Metabolism 281, E649-54 (2001)).The ability that these neurone perception glucose levels change is (Spanswick, D.et al, the Nature Neuroscience that lacks in multiple heredity with testing in the fat model of bringing out property 3, 757-8 (2000), Levin, B.E.et al, Brain Research 808, 317-9 (1998)).Intraventricular (icv) infusion of glucalogue (they are competitive inhibitors of glucokinase) has stimulated ingestion of food (Kurata, K.et al, the Metabolism:Clinical ﹠amp of thin type rat; Experimental 38, 46-51 (1989)).By contrast, the icv infusion of glucose suppresses to ingest (Kurata, K.et al, Physiology ﹠amp; Behavior 37, 615-20 (1986)).The small molecules activator of GK thereby can reduce ingestion of food and weightening finish by the maincenter effect to GK.Therefore, except diabetes, the GK activator can also treated eating disorder, comprise that having treatment in the obesity uses.The hypothalamus effect of same compound and liver and/or pancreas effect will make aspect the glucose homeostasis normalizing be additivity or synergitic, be used for the treatment of diabetes B.Thereby GK/GK regulates the potential target that protein system can be called as is of value to diabetes and obesity.

Glucose-amplitude of inducing Regular Insulin to discharge depends on the effect of gastrointestinal hormone ` GLP-1 (glycogen sample peptide 1) and GIP greatly.Different with the sulfonylurea that stimulates Regular Insulin to discharge under low and high glucose level, the effect of the beta cell of GLP-1 is dependent (Gromada, J.et al., Pfl ü gers Arch of glucose 435, 583-594 (1998)).Therefore the GLP-1 receptor stimulant is the novel treatment means that is in the diabetes B in the exploitation with the medicine that slows down active GLP-1 degraded.Alternative strategy will be to improve endogenous GLP-1 level.Potential relevant be that the release of GLP-1 and GIP may be subjected to glucokinase-expressivity endocrine cell (Jetton, T.L.et al., J.Biol.Chem. 269, 3641-3654 (1994)) and glucose-responsiveness neurone (Liu, M.et al., J.Neurosci. 19, 10305-10317 (1999)) and the possibility of regulating.Someone has reported that intestines K-cell discharges control (Kieffer, T.J.et al., the Am J Physiol that GIP directly is subjected to glucose 267, E489-E496 (1994)), GLUTag emiocytosis GLP-1 is subjected to the initiation of glucose, and its mechanism is similar to insulin secretion (Reimann, F.et al, the Diabetes in the beta cell 51, 2757-2763 (2002)).The small molecules activator of glucokinase thereby can be for increasing GLP-1 and/or GIP secretion, thus be used for the treatment of, regulate and control, suppress, reduce, reduce, stop or prevent beta cell sex change, for example necrosis of beta cell or apoptosis.

The invention provides heteroaryl and aryl urea or acid amides or the sulphonamide activator of the ortho position-replacement of glucokinase.

In first kind of embodiment, the invention provides general formula (I) compound

Wherein

A ¹Be selected from the group of being formed by arylidene, inferior heteroaryl, fused rings alkyl arylidene, annelated heterocycles base arylidene, fused rings alkyl inferior heteroaryl or annelated heterocycles base inferior heteroaryl; Wherein alternatively by one or more substituent R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-, heteroaryl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl;

Perhaps

R ²And R ³When being connected with same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, it contains one or two extra heteroatoms that is selected from nitrogen, oxygen and sulphur alternatively, and contains one or two two keys alternatively;

Z and W ¹Be independently of one another direct key ,-O-,-N (R ⁷)-,-S-,-SO ₂-,-C (O) N (R ⁷)-,-N (R ⁷) C (O)-,-N (R ⁷) CON (R ⁸)-,-N (R ⁷) SO ₂-,-SO ₂N (R ⁷)-,-C (O)-O-,-N (R ⁷) SO ₂N (R ⁸)-or-O-C (O)-, wherein

R ⁷And R ⁸Be hydrogen or alkyl independently of one another under every kind of individual cases;

R ⁴, R ⁵And R ⁶Be independently from each other the group by hydrogen, aryl, alkyl, heteroaryl-alkylidene group-and aryl-alkylidene group-form;

Perhaps

R ⁴And R ⁵Can constitute together and have formula-(CH ₂) _j-Q-(CH ₂) _k-ring, be bonded to R ⁴And R ⁵The nitrogen-atoms place that connects, wherein

J and k are 1,2,3 or 4 independently of one another;

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be independently from each other the group by hydrogen, aryl, alkyl and aryl-alkylidene group-form;

L ¹Be-D-alkylidene group-E-,-D-alkenylene-E-,-D-alkynylene-E-,-the inferior cyclic hydrocarbon radical-E-of D-,-the inferior heterocyclic radical-E-of D-,-O-,-S-,-S (O)-,-S (O) ₂-,-C (O)-,-N (R ¹¹)-or-C (=N-OR ¹²)-, wherein

D and E be independently of one another direct key ,-O-or-S-;

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, heteroaryl-alkylidene group-, alkyl-O-C (O)-, aryl-alkylidene group-O-C (O)-, heteroaryl-alkylidene group-O-C (O)-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, heteroaryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, heteroaryl-alkylidene group-SO ₂-, aryl-SO ₂-, heteroaryl-SO ₂-, alkyl-NH-SO ₂-, aryl-alkylidene group-NH-SO ₂-, heteroaryl-alkylidene group-NH-SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, heteroaryl-alkylidene group-C (O)-, alkyl-Y-, aryl-Y-, heteroaryl-Y-, aryl-alkylidene group-Y-, heteroaryl-alkylidene group-Y-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, heteroaryl, C _1-6-alkyl, C _1-6-alkoxyl group, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkoxyl group-, heteroaryl-C _1-6-alkoxyl group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-inferior heteroaryl-or C _1-6-alkoxyl group-arylidene-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, be bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another; And

X be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-CON (H)-,-NHC (O)-,-NHCON (H)-,-NHSO ₂-,-SO ₂N (H)-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ¹⁶And R ¹⁷Be selected from hydrogen, aryl, heteroaryl, C _1-6-alkyl, C _1-6-alkoxyl group, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-arylidene-, C _1-6-alkoxyl group-inferior heteroaryl-, heteroaryl aryl-C _1-6-alkoxyl group-or aryl-C _1-6-alkoxyl group-;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl, heteroaryl-alkylidene group-or aryl-alkylidene group-form;

R ¹²Be selected from hydrogen, aryl, heteroaryl, alkyl, aryl-alkylidene group-, heteroaryl-alkylidene group-, alkyl-arylidene-, alkyl-inferior heteroaryl-, alkoxyl group-inferior heteroaryl-or alkoxyl group-arylidene-;

G ¹Be alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical or heterocyclic radical,

Replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹, C _3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6--alkyl-inferior heteroaryl-, heteroaryl or aryl;

Perhaps

R ¹⁸And R ¹⁹In the time of on being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, it contains one or two extra heteroatoms that is selected from nitrogen, oxygen and sulphur alternatively, and contains one or two two keys alternatively;

Perhaps

G ¹Be aryl, heteroaryl, fused rings alkyl heteroaryl, annelated heterocycles Ji Fangji or fused rings alkylaryl,

Alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace;

L ²Be direct key, alkylidene group, alkenylene, alkynylene ,-N (R ²⁰)-,-alkylidene group-N (R ²⁰)-,-alkenylene-N (R ²⁰)-,-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be hydrogen, perhaps

R ²⁰Be alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical-W ³-, heterocyclic radical-W ³-, aryl-W ³-, heteroaryl-W ³-, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

W ³Be alkylidene group or direct key;

L wherein ¹And L ²Be connected in A ¹In adjacent atom;

L ³Be-C (O)-or-S (O) ₂-;

R ¹Be hydrogen, perhaps

R ¹Be alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical-W ⁴-, heterocyclic radical-W ⁴-, aryl-W ⁴-or heteroaryl-W ⁴-,

Alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

W ⁴Be alkylidene group or direct key;

G ²Be heteroaryl, annelated heterocycles base heteroaryl or fused rings alkyl heteroaryl,

Alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possess with is connected described heteroaryl and-N (R ¹)-the adjacent nitrogen-atoms of atom;

Or following formula group

Wherein

G ³And G ⁵Be alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical-R independently of one another ²²-, heterocyclic radical-R ²²-, aryl-R ²²-, heteroaryl-R ²²-,

Alternatively by one or more substituent R ⁴⁶, R ⁴⁷And R ⁴⁸Replace, wherein

R ²²Be alkylidene group or direct key;

R ²¹Be hydrogen, alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical-W ⁵-or heterocyclic radical-W ⁵,

Alternatively by one or more substituent R ³⁶, R ³⁷And R ³⁸Replace, perhaps

R ²¹Be aryl-W ⁵-or heteroaryl-W ⁵-, it is alternatively by one or more substituent R ⁴⁹, R ⁵⁰And R ⁵¹Replace, wherein

W ⁵Be alkylidene group or direct key;

Wherein

R ³⁰, R ³¹, R ³², R ³³, R ³⁴, R ³⁵, R ³⁶, R ³⁷And R ³⁸Be independently from each other-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵²,-NR ⁵²R ⁵³,-SR ⁵²,-NR ⁵²S (O) ₂R ⁵³,-S (O) ₂NR ⁵²R ⁵³,-S (O) NR ⁵²R ⁵³,-S (O) R ⁵²,-S (O) ₂R ⁵²,-C (O) NR ⁵²R ⁵³,-OC (O) NR ⁵²R ⁵³,-NR ⁵²C (O) R ⁵³,-CH ₂C (O) NR ⁵²R ⁵³,-OCH ₂C (O) NR ⁵²R ⁵³,-CH ₂OR ⁵²,-CH ₂NR ⁵²R ⁵³,-OC (O) R ⁵²,-C (O) R ⁵²With-C (O) OR ⁵²Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵²,-NR ⁵²R ⁵³And C _1-6-alkyl; Perhaps

C _3-10-cyclic hydrocarbon radical, C _4-8-cycloalkenyl group, heterocyclic radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylthio-, C _3-10-cyclic hydrocarbon sulfenyl, C _3-10-cyclic hydrocarbon radical-C _2-6-alkenylene-, C _3-10-cyclic hydrocarbon radical-C _2-6-alkynylene-, C _4-8-cycloalkenyl group-C _1-6-alkylidene group-, C _4-8-cycloalkenyl group-C _2-6-alkenylene-, C _4-8-cycloalkenyl group-C _2-6-alkynylene-, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical-C _2-6-alkenylene-, heterocyclic radical-C _2-6-alkynylene-, aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, aryl-C _2-6-alkenylene-, aryl-C _2-6-alkynylene-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, heteroaryl-C _2-6-alkenylene-and heteroaryl-C _2-6-alkynylene-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵²,-NR ⁵²R ⁵³And C _1-6-alkyl, wherein

R ⁵²With ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-heteroaryl-C _1-6-alkylidene group-heteroaryl or aryl;

Perhaps

R ⁵²And R ⁵³In the time of on being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, it contains one or two extra heteroatoms that is selected from nitrogen, oxygen and sulphur alternatively, and contains one or two two keys alternatively;

R ⁴⁰, R ⁴¹, R ⁴², R ⁴³, R ⁴⁴, R ⁴⁵, R ⁴⁶, R ⁴⁷, R ⁴⁸, R ⁴⁹, R ⁵⁰And R ⁵¹Be independently of one another halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵,-OC (O) R ⁵⁴,-C (O) R ⁵⁴With-C (O) OR ⁵⁴Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl;

C _3-10-cyclic hydrocarbon radical, C _4-8-cycloalkenyl group, heterocyclic radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylthio-, C _3-10-cyclic hydrocarbon sulfenyl, C _3-10-cyclic hydrocarbon radical-C _2-6-alkenylene-, C _3-10-cyclic hydrocarbon radical-C _2-6-alkynylene-, C _4-8-cycloalkenyl group-C _1-6-alkylidene group-, C _4-8-cycloalkenyl group-C _2-6-alkenylene-, C _4-8-cycloalkenyl group-C _2-6-alkynylene-, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical-C _2-6-alkenylene-, heterocyclic radical-C _2-6-alkynylene-; Perhaps

Aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, aryl-C _2-6-alkenylene-, aryl-C _2-6-alkynylene-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, heteroaryl-C _2-6-alkenylene-and heteroaryl-C _2-6-alkynylene-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁶³) ₇-(CHR ⁶⁴) _v-Z, wherein

U is 1 or 2;

V is 0,1 or 2;

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-aryl, hydroxyl, hydroxyalkyl, amino or aminoalkyl group;

Z be hydrogen ,-O-R ⁶⁵,-C (O) O-R ⁶⁵,-CONR ⁶⁵R ⁶⁶, alkylamino or dialkyl amido, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl;

Perhaps

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen;

Perhaps

R ⁵⁴And R ⁵⁵In the time of on being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively, also alternatively by one or more C _1-6-alkyl replaces;

Perhaps its pharmacy acceptable salt, solvate or prodrug.

Other embodiments of the present invention can be apparent from following embodiment tabulation.

Embodiment 2: according to the compound of embodiment 1, wherein

A ¹Be arylidene or inferior heteroaryl, it is alternatively by one or more substituent R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-, heteroaryl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as enforcement mode 1.

Embodiment 3: according to the compound of embodiment 2, wherein

A ¹Be C _6-10-arylidene or C _4-10-inferior heteroaryl, it is alternatively by one or more substituent R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-, heteroaryl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as enforcement mode 1.

Embodiment 4: according to the compound of any embodiment 1 to 3, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as enforcement mode 1.

Embodiment 5: according to the compound of any embodiment 1 to 4, wherein

R ⁴, R ⁵And R ⁶Be independently from each other the group by hydrogen, aryl, alkyl, heteroaryl-alkylidene group-and aryl-alkylidene group-form.

Embodiment 6: according to the compound of embodiment 5, wherein

R ⁴, R ⁵And R ⁶Be hydrogen or alkyl independently of one another.

Embodiment 7: according to the compound of embodiment 6, wherein

R ⁴, R ⁵And R ⁶Be hydrogen.

Embodiment 8: according to the compound of any embodiment 1 to 4, wherein

R ⁴And R ⁵Constitute together and have formula-(CH ₂) _j-Q-(CH ₂) _k-ring, be bonded to R ⁴And R ⁵The nitrogen-atoms place that connects, wherein

J and k are 1,2,3 or 4 independently of one another;

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be independently from each other the group by hydrogen, aryl, alkyl and arylalkyl-form.

Embodiment 9: according to the compound of embodiment 8, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be hydrogen or alkyl independently of one another.

Embodiment 10: according to the compound of embodiment 9, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Embodiment 11: according to the compound of embodiment 10, wherein Q is direct key.

Embodiment 12: according to the compound of any embodiment 1 to 11, wherein

W ¹Be direct key ,-O-,-NH-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment 13: according to the compound of embodiment 12, wherein W ¹Be direct key ,-O-,-S-or-SO ₂-.

Embodiment 14: according to the compound of embodiment 13, wherein W ¹It is direct key.

Embodiment 15: according to the compound of embodiment 4, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, wherein

R ², R ³With Z be defined as enforcement mode 1.

Embodiment 16: according to the compound of embodiment 15, wherein

R ²³⁰, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as enforcement mode 1.

Embodiment 17: according to the compound of embodiment 16, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as enforcement mode 1.

Embodiment 18: according to the compound of embodiment 17, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²Or-NR ²R ³, wherein

R ², R ³With Z be defined as enforcement mode 1.

Embodiment 19: according to the compound of any embodiment 1 to 18, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment 20: according to the compound of embodiment 19, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 21: according to the compound of embodiment 20, wherein

R ²Be hydrogen or C _1-6-alkyl.

Embodiment 22: according to the compound of embodiment 21, wherein

R ²Be hydrogen.

Embodiment 23: according to the compound of any embodiment 1 to 22, wherein

R ³Be hydrogen or C _1-6-alkyl.

Embodiment 24: according to the compound of embodiment 23, wherein

R ³Be hydrogen.

Embodiment 25: according to the compound of any embodiment 1 to 15, wherein

R ²And R ³When being connected with same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms-rise, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 26: according to the compound of any embodiment 1 to 25, wherein

Z be direct key ,-O-,-NH-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment 27: according to the compound of embodiment 26, wherein

Z be direct key ,-O-,-S-or-SO ₂-.

Embodiment 28: according to the compound of embodiment 27, wherein

Z is direct key.

Embodiment 29: according to the compound of embodiment 2, wherein

A ¹Be

Wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Be hydrogen or defined as enforcement mode 1 independently of one another.

Embodiment 30: according to the compound of embodiment 29, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as enforcement mode 1.

Embodiment 31: according to the compound of embodiment 29 or 30, wherein

R ⁴, R ⁵And R ⁶Be independently from each other the group by hydrogen, aryl, alkyl, heteroaryl-alkylidene group-and aryl-alkylidene group-form.

Embodiment 32: according to the compound of embodiment 31, wherein

R ⁴, R ⁵And R ⁶Be hydrogen or alkyl independently of one another.

Embodiment 33: according to the compound of embodiment 32, wherein

R ⁴, R ⁵And R ⁶Be hydrogen.

Embodiment 34: according to the compound of embodiment 29 or 30, wherein

R ⁴And R ⁵Constitute together and have formula-(CH ₂) _j-Q-(CH ₂) _k-ring, be bonded to R ⁴And R ⁵The nitrogen-atoms place that connects, wherein

J and k are 1,2,3 or 4 independently of one another;

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be independently from each other the group by hydrogen, aryl, alkyl and arylalkyl-form.

Embodiment 35: according to the compound of embodiment 34, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be hydrogen or alkyl independently of one another.

Embodiment 36: according to the compound of embodiment 35, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Embodiment 37: according to the compound of embodiment 36, wherein

Q is direct key.

Embodiment 38: according to the compound of any embodiment 29 to 37, wherein

W ¹Be direct key ,-O-,-NH-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment 39: according to the compound of embodiment 38, wherein

W ¹Be direct key ,-O-,-S-or-SO ₂-.

Embodiment 40: according to the compound of embodiment 39, wherein

W ¹It is direct key.

Embodiment 41: according to the compound of embodiment 29, wherein

R ²³, R ²⁴, R ²⁵And R ⁴⁶Have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, wherein

R ², R ³With Z be defined as enforcement mode 29.

Embodiment 42: according to the compound of embodiment 41, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as enforcement mode 29.

Embodiment 43: according to the compound of embodiment 42, wherein

R ²³, R ²⁴, R ²²And R ²⁶Have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as enforcement mode 29.

Embodiment 44: according to the compound of any embodiment 29 to 43, wherein

Z be direct key ,-O-,-NH-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment 45: according to the compound of embodiment 44, wherein

Z be direct key ,-O-,-S-or-SO ₂-.

Embodiment 46: according to the compound of embodiment 45, wherein

Z is direct key.

Embodiment 47: according to the compound of embodiment 43, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²,-NR ²R ³Or C _1-6-alkyl, wherein

R ²And R ³Be defined as enforcement mode 29.

Embodiment 48: according to the compound of any embodiment 29 to 47, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment 49: according to the compound of embodiment 48, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 50: according to the compound of embodiment 49, wherein

R ²Be hydrogen or C _1-6-alkyl.

Embodiment 51: according to the compound of embodiment 50, wherein

R ²Be hydrogen.

Embodiment 52: according to the compound of any embodiment 29 to 51, wherein

R ³Be hydrogen or C _1-6-alkyl.

Embodiment 53: according to the compound of embodiment 52, wherein

R ³Be hydrogen.

Embodiment 54: according to the compound of any embodiment 29 to 41, wherein

R ²And R ³When being connected with same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 55: according to the compound of any embodiment 29 to 46, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Have at least one to be hydrogen.

Embodiment 56: according to the compound of embodiment 55, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least two to be hydrogen.

Embodiment 57. is according to the compound of claim 56, wherein

R ²³And R ²⁶Be hydrogen.

Embodiment 58: according to the compound of embodiment 56 or claim 57, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least three to be hydrogen.

Embodiment 59: according to the compound of any embodiment 29 to 58, wherein R ²⁴Or R ²⁵It is halogen.

Embodiment 60: according to the compound of embodiment 59, wherein R ²⁴Or R ²⁵It is fluorine.

Embodiment 61: according to the compound of any embodiment 29 to 58, wherein R ²⁴Or R ²⁵Be C _1-6-alkyl.

Embodiment 62: according to the compound of embodiment 59, wherein R ²⁴Or R ²⁵It is methyl.

Embodiment 63: according to the compound of any embodiment 29 to 58, wherein

R ²⁴Be hydrogen.

Embodiment 64: according to the compound of any embodiment 29 to 63, wherein

R ²⁵Be hydrogen.

Embodiment 65: according to the compound of embodiment 29, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Be hydrogen.

Embodiment 66: according to the compound of any embodiment 1 to 65, wherein

L ¹Be-D-alkylidene group-E-,-O-,-S-,-S (O)-,-S (O) ₂-,-C (O)-,-N (R ¹¹)-or-C (=N-OR ¹²), wherein

D, E, R ¹¹And R ¹²Be defined as enforcement mode 1.

Embodiment 67: according to the compound of embodiment 66, wherein

L ¹Be-D-alkylidene group-E-,-O-,-C (O)-,-N (R ¹¹)-or-C (=N-OR ¹²)-, wherein

D, E, R ¹¹And R ¹²Be defined as enforcement mode 1.

Embodiment 68: according to the compound of embodiment 66, wherein

L ¹Be-O-.

Embodiment 69: according to the compound of embodiment 66, wherein

L ¹Be-S-.

Embodiment 70: according to the compound of embodiment 66, wherein

L ¹Be-C (O)-.

Embodiment 71: according to the compound of any embodiment 1 to 67, wherein

D be direct key or-O-;

E be direct key or-O-;

R ¹¹And R ¹²Be defined as enforcement mode 1.

Embodiment 72: according to the compound of embodiment 71, wherein

D is direct key.

Embodiment 73: according to the compound of embodiment 71, wherein

D is-O-.

Embodiment 74: according to the compound of any embodiment 71 to 73, wherein

E is direct key.

Embodiment 75: according to the compound of any embodiment 71 to 73, wherein

E is-O-.

Embodiment 76: according to the compound of any embodiment 1 to 75, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, be bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-CON (H)-,-NHC (O)-,-NHCON (H)-,-NHSO ₂-,-SO ₂N (H)-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ¹⁶And R ¹⁷Be selected from hydrogen, aryl, heteroaryl, C _1-6-alkyl, C _1-6-alkoxyl group, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-arylidene-, C _1-6-alkoxyl group-inferior heteroaryl-, heteroaryl aryl-C _1-6-alkoxyl group-or aryl-C _1-6-alkoxyl group-;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 77: according to the compound of embodiment 76, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, this ring is bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-CON (H)-,-NHC (O)-,-NHCON (H)-,-NHSO ₂-,-SO ₂N (H)-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ¹⁶And R ¹⁷Be hydrogen;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 78: according to the compound of embodiment 77, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, this ring is bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X is direct key; And

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 79: according to the compound of embodiment 78, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 80: according to the compound of embodiment 79, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be hydrogen;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 81: according to the compound of embodiment 80, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y is direct key;

W ²Be direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be hydrogen;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 82: according to the compound of embodiment 80, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-alkylidene group-Y-and R ¹⁵-W ²-alkylidene group-Y-, wherein

Y be direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

W ²It is direct key;

R ¹³And R ¹⁴Be hydrogen;

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 83: according to the compound of any embodiment 80 to 82, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-, NH ₂-alkylidene group-and R ¹⁵-alkylidene group-, wherein

R ¹⁵Be selected from the group by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, alkyl or aryl-alkylidene group-form.

Embodiment 84: according to the compound of embodiment 83, wherein

R ¹¹Be selected from hydrogen, alkyl, aryl, carbamyl, aryl-alkylidene group-, alkyl-NH-C (O)-, aryl-alkylidene group-NH-C (O)-, alkyl-SO ₂-, aryl-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, alkyl-C (O)-, aryl-alkylidene group-C (O)-and NH ₂-alkylidene group-.

Embodiment 85: according to the compound of embodiment 84, wherein

R ¹¹It is hydrogen or alkyl.

Embodiment 86: according to the compound of embodiment 85, wherein

R ¹¹Be hydrogen.

Embodiment 87: according to the compound of any embodiment 1 to 86, wherein

R ¹²It is hydrogen or alkyl.

Embodiment 88: according to the compound of embodiment 87, wherein

R ¹²Be hydrogen.

Embodiment 89: according to the compound of any embodiment 1 to 88, wherein

G ¹Be alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical or heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹, C _3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as enforcement mode 1.

Embodiment 90: according to the compound of embodiment 89, wherein

G ¹Be alkyl, thiazolinyl, alkynyl, cyclic hydrocarbon radical or heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as enforcement mode 1.

Embodiment 91: according to the compound of embodiment 89, wherein

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical or C _3-10-heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹, C ^3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as enforcement mode 1.

Embodiment 92: according to the compound of embodiment 90 or embodiment 91, wherein

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical or C _3-10-heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as enforcement mode 1.

Embodiment 93: according to the compound of any embodiment 89 to 92, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment 94: according to the compound of embodiment 93, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-aryl-C _1-6-alkylidene group-, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment 95: according to the compound of embodiment 94, wherein

R ¹⁸And R ¹⁹Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 96: according to the compound of embodiment 95, wherein

R ¹⁸Be hydrogen.

Embodiment 97: according to the compound of embodiment 95 or 96, wherein

R ¹⁹Be hydrogen.

Embodiment 98: according to the compound of embodiment 90 or embodiment 92, wherein

R ¹⁸And R ¹⁹When being connected in same nitrogen-atoms, constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 99: according to the compound of any embodiment 1 to 88, wherein

G ¹Be alkyl or cyclic hydrocarbon radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed,

Perhaps G ¹Be aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein R ¹⁸, R ¹⁹, R ⁴⁰, R ⁴¹And R ⁴²Be defined as enforcement mode 1.

Embodiment 100: according to the compound of embodiment 99, wherein

G ¹Be C _1-6-alkyl or C _3-10-cyclic hydrocarbon radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed,

Perhaps G ¹Be C _3-10-aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein R ¹⁸, R ¹⁹, R ⁴⁰, R ⁴¹And R ⁴²Be defined as enforcement mode 1.

Embodiment 101: according to the compound of embodiment 99 or embodiment 100, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment 102: according to the compound of embodiment 101, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-aryl-C _1-6-alkylidene group-, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment 103: according to the compound of embodiment 102, wherein

R ¹⁸And R ¹⁹Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 104: according to the compound of embodiment 103, wherein

R ¹⁸Be hydrogen.

Embodiment 105: according to the compound of embodiment 103 or 104, wherein

R ¹⁹Be hydrogen.

Embodiment 106: according to the compound of embodiment 99 or embodiment 100, wherein

R ¹⁸And R ¹⁹When being connected in same nitrogen-atoms, constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 107: according to the compound of any embodiment 99 to 106, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵With-C (O) OR ⁵⁴Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 108: according to the compound of embodiment 107, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-aryl-C _1-6-alkylidene group-, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment 109: according to the compound of embodiment 108, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 110: according to the compound of embodiment 109, wherein

R ⁵⁴Be hydrogen.

Embodiment 111: according to the compound of embodiment 109 or embodiment 110, wherein

R ⁵⁵Be hydrogen.

Embodiment 112: according to the compound of any embodiment 1 to 88, wherein

G ¹Be aryl or heteroaryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as enforcement mode 1.

Embodiment 113: according to the compound of embodiment 112, wherein

G ¹Be C _3-10-aryl or C _3-10-heteroaryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as enforcement mode 1.

Embodiment 114: according to the compound of embodiment 112, wherein

G ¹Be aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as enforcement mode 1.

Embodiment 115: according to the compound of embodiment 114, wherein

G ¹Be C _3-10-aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as enforcement mode 1.

Embodiment 116: according to the compound of any embodiment 112 to 115, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵With-C (O) OR ⁵⁴Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 117: according to the compound of embodiment 116, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-aryl-C _1-6-alkylidene group-, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment 118: according to the compound of embodiment 117, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 119: according to the compound of embodiment 118, wherein

R ⁵⁴Be hydrogen.

Embodiment 120: according to the compound of embodiment 118 or embodiment 119, wherein

R ⁵⁵Be hydrogen.

Embodiment 121: according to the compound of embodiment 114, wherein

G ¹Be

Wherein

R ⁵⁶, R ⁵⁷, R ⁵⁸, R ⁵⁹And R ⁶⁰Be independently of one another hydrogen or halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²,-SR ⁶¹,-NR ⁶¹S (O) ₂R ⁶²,-S (O) ₂NR ⁶¹R ⁶²,-S (O) NR ⁶¹R ⁶²,-S (O) R ⁶¹,-S (O) ₂R ⁶¹,-C (O) NR ⁶¹R ⁶²,-OC (O) NR ⁶¹R ⁶²,-NR ⁶¹C (O) R ⁶²,-CH ₂C (O) NR ⁶¹R ⁶²,-CH ₂C (O) OR ⁶¹,-OCH ₂C (O) NR ⁶¹R ⁶²,-CH ₂OR ⁶¹,-CH ₂NR ⁶¹R ⁶²,-OC (O) R ⁶¹,-C (O) R ⁶¹With-C (O) OR ⁶¹Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²And C _1-6-alkyl;

C _3-10-cyclic hydrocarbon radical, C _4-8-cycloalkenyl group, heterocyclic radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylthio-, C _3-10-cyclic hydrocarbon sulfenyl, C _3-10-cyclic hydrocarbon radical-C _2-6-alkenylene-, C _3-10-cyclic hydrocarbon radical-C _2-6-alkynylene-, C _4-8-cycloalkenyl group-C _1-6-alkylidene group-, C _4-8-cycloalkenyl group-C _2-6-alkenylene-, C _4-8-cycloalkenyl group-C _2-6-alkynylene-, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical-C _2-6-alkenylene-, heterocyclic radical-C _2-6-alkynylene-; Perhaps

Aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, aryl-C _2-6-alkenylene-, aryl-C _2-6-alkynylene-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, heteroaryl-C _2-6-alkenylene-and heteroaryl-C _2-6-alkynylene-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁶¹,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁶¹,-NR ⁶¹R ⁶²Or C _1-6-alkyl, wherein

R ⁶¹And R ⁶²Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁶¹And R ⁶²When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 122: according to the compound of embodiment 121, wherein

R ⁵⁶, R ⁵⁷, R ⁵⁸, R ⁵⁹And R ⁶⁰Be independently of one another

Halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²,-SR ⁶¹,-NR ⁶¹S (O) ₂R ⁶²,-S (O) ₂NR ⁶¹R ⁶²,-S (O) NR ⁶¹R ⁶²,-S (O) R ⁶¹,-S (O) ₂R ⁶¹,-C (O) NR ⁶¹R ⁶²,-OC (O) NR ⁶¹R ⁶²,-NR ⁶¹C (O) R ⁶²,-CH ₂C (O) NR ⁶¹R ⁶²,-CH ₂C (O) OR ⁶¹,-OCH ₂C (O) NR ⁶¹R ⁶²,-CH ₂OR ⁶¹,-CH ₂NR ⁶¹R ⁶²With-C (O) OR ⁶¹Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²And C _1-6-alkyl, wherein

R ⁶¹And R ⁶²Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁶¹And R ⁶²When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 123: according to the compound of embodiment 121 or embodiment 122, wherein R ²⁴Or R ²⁵Be-OR ⁶¹

Embodiment 124: according to the compound of embodiment 122, wherein

R ⁶¹And R ⁶²Be hydrogen or C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-aryl-C _1-6-alkylidene group-, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment 125: according to the compound of embodiment 124, wherein

R ⁶¹And R ⁶²Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 126: according to the compound of embodiment 125, wherein

R ⁶¹Be hydrogen.

Embodiment 127: according to the compound of embodiment 125 or embodiment 126, wherein

R ⁶²Be hydrogen.

Embodiment 128: according to the compound of any embodiment 121 to 127, wherein

R ⁵⁶, R ⁵⁷, R ⁵⁸, R ⁵⁹And R ⁶⁰In have at least one to be hydrogen.

Embodiment 129: according to the compound of embodiment 128, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least two to be hydrogen.

Embodiment 130: according to the compound of embodiment 129, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least three to be hydrogen.

Embodiment 131: according to the compound of any embodiment 1 to 130, wherein

L ²Be direct key, C _1-6-alkylidene group, C _2-6-alkenylene, C _2-6-alkynylene ,-N-R ²⁰-,-C _1-6-alkylidene group-N (R ²⁰)-,-C _2-6-alkenylene-N (R ²⁰)-or-C _2-6-alkynylene-N (R ²⁰)-,

Wherein

R ²⁰Be defined as enforcement mode 1.

Embodiment 132: according to the compound of any embodiment 1 to 127, wherein

L ²Be-N-R ²⁰-,-alkylidene group-N (R ²⁰)-,-alkenylene-N (R ²⁰)-or-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be defined as enforcement mode 1.

Embodiment 133: according to the compound of embodiment 131 or embodiment 132, wherein

L ²Be-N-R ²⁰-,-C _1-6-alkylidene group-N (R ²⁰)-,-C _2-6-alkenylene-N (R ²⁰)-or-C _2-6-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be defined as enforcement mode 1.

Embodiment 134: according to the compound of embodiment 133, wherein

L ²Be-N-R ²⁰-, wherein

R ²⁰Be defined as enforcement mode 1.

Embodiment 135: according to the compound of embodiment 131, wherein

L ²It is direct key.

Embodiment 136: according to the compound of any embodiment 1 to 134, wherein

R ²⁰Be hydrogen, perhaps

R ²⁰Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical-W ³, C _3-10-heterocyclic radical-W ³, C _3-10-aryl-W ³-or C _4-10-heteroaryl-W ³-, wherein alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

W ³, R ³⁰, R ³¹And R ³²Be defined as enforcement mode 1.

Embodiment 137: according to the compound of embodiment 136, wherein

W ³It is alkylidene group.

Embodiment 138: according to the compound of embodiment 137, wherein

W ³Be C _2-6-alkylidene group.

Embodiment 139: according to the compound of embodiment 136, wherein

W ³It is direct key.

Embodiment 140: according to the compound of any embodiment 1 to 134, wherein

R ²⁰Be hydrogen, alkyl, alkenyl or alkynyl, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

R ³⁰, R ³¹And R ³²Be defined as enforcement mode 1.

Embodiment 141: according to the compound of any embodiment 136 to 140, wherein

R ²⁰Be hydrogen, perhaps

R ²⁰Be C _1-6-alkyl, C _1-6-thiazolinyl or C _1-6-alkynyl, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

R ³⁰, R ³¹And R ³²Be defined as enforcement mode 1.

Embodiment 142: according to the compound of any embodiment 1 to 141, wherein

R ³⁰, R ³¹And R ³²Be independently from each other-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵²,-NR ⁵²R ⁵³,-SR ⁵²,-NR ⁵²S (O) ₂R ⁵³,-S (O) ₂NR ⁵²R ⁵³,-S (O) NR ⁵²R ⁵³,-S (O) R ⁵²,-S (O) ₂R ⁵²,-C (O) NR ⁵²R ⁵³,-OC (O) NR ⁵²R ⁵²,-NR ⁵²C (O) R ⁵³,-CH ₂C (O) NR ⁵²R ⁵³,-OCH ₂C (O) NR ⁵²R ⁵³,-CH ₂OR ⁵²,-CH ₂NR ⁵²R ⁵³,-OC (O) R ⁵²,-C (O) R ⁵²With-C (O) OR ⁵², wherein

R ⁵²And R ⁵³Be defined as enforcement mode 1.

Embodiment 143: according to the compound of embodiment 142, wherein

R ⁵²And R ⁵³When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 144: according to the compound of any embodiment 1 to 142, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-heteroaryl-C _1-6-alkylidene group-heteroaryl or aryl.

Embodiment 145: according to the compound of embodiment 144, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 146: according to the compound of embodiment 145, wherein

R ⁵²And R ⁵³Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 147: according to the compound of embodiment 146, wherein

R ⁵²Be hydrogen.

Embodiment 148: according to the compound of embodiment 146 or embodiment 147, wherein

R ⁵³Be hydrogen.

Embodiment 149: according to the compound of embodiment 141, wherein

R ²⁰Be hydrogen.

Embodiment 150: according to the compound of any embodiment 1 to 149, wherein

L ³Be-C (O)-.

Embodiment 151: according to the compound of any embodiment 1 to 150, wherein

R ¹Be hydrogen, perhaps

R ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical-W ⁴-, C _3-10-heterocyclic radical-W ⁴-, C _3-10-aryl-W ⁴-or C _4-10-heteroaryl-W ⁴-, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

W ⁴, R ³³, R ³⁴And R ³⁵Be defined as enforcement mode 1.

Embodiment 152: according to the compound of embodiment 151, wherein

W ⁴It is alkylidene group.

Embodiment 153: according to the compound of embodiment 152, wherein

W ⁴Be C _2-6-alkylidene group.

Embodiment 154: according to the compound of embodiment 151, wherein

W ⁴It is direct key.

Embodiment 155: according to the compound of any embodiment 1 to 150, wherein

R ¹Be hydrogen, alkyl, alkenyl or alkynyl, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

R ³³, R ³⁴And R ³⁵Be defined as enforcement mode 1.

Embodiment 156: according to the compound of any embodiment 151 to 155, wherein

R ¹Be hydrogen, C _1-6-alkyl, C _2-6-thiazolinyl or C _2-6-alkynyl, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

R ³³, R ³⁴And R ³⁵Be defined as enforcement mode 1.

Embodiment 157: according to the compound of embodiment 156, wherein

R ¹Be hydrogen or C _1-6-alkyl, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

R ³³, R ³⁴And R ³⁵Be defined as enforcement mode 1.

Embodiment 158: according to the compound of any embodiment 1 to 157, wherein

R ³³, R ³⁴And R ³⁵Be independently from each other-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵²,-NR ⁵²R ⁵³,-SR ⁵²,-NR ⁵²S (O) ₂R ⁵³,-S (O) ₂NR ⁵²R ⁵³,-S (O) NR ⁵²R ⁵³,-S (O) R ⁵²,-S (O) ₂R ⁵²,-C (O) NR ⁵²R ⁵³,-OC (O) NR ⁵²R ⁵³,-NR ⁵²C (O) R ⁵³,-CH ₂C (O) NR ⁵²R ⁵³,-OCH ₂C (O) NR ⁵²R ⁵³,-CH ₂OR ⁵²,-CH ₂NR ⁵²R ⁵³,-OC (O) R ⁵²,-C (O) R ⁵²With-C (O) OR ⁵², wherein

R ⁵²And R ⁵³Be defined as enforcement mode 1.

Embodiment 159: according to the compound of embodiment 157, wherein

R ⁵²And R ⁵³When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 160: according to the compound of embodiment 157, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-heteroaryl-C _1-6-alkylidene group-heteroaryl or aryl.

Embodiment 161: according to the compound of embodiment 160, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 162: according to the compound of embodiment 161, wherein

R ⁵²And R ⁵³Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 163: according to the compound of embodiment 162, wherein

R ⁵²Be hydrogen.

Embodiment 164: according to the compound of embodiment 162 or embodiment 163, wherein

R ⁵³Be hydrogen.

Embodiment 165: according to the compound of embodiment 157, wherein

R ¹Be hydrogen.

Embodiment 166: according to the compound of any embodiment 1 to 165, wherein

G ²Be heteroaryl, annelated heterocycles base heteroaryl or fused rings alkyl heteroaryl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possesses and is connected G ²With-N (R ¹)-the adjacent nitrogen-atoms of atom, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as enforcement mode 1.

Embodiment 167: according to the compound of embodiment 166, wherein

G ²Be heteroaryl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possesses and is connected G ²With-N (R ¹)-the adjacent nitrogen-atoms of atom, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as enforcement mode 1.

Embodiment 168: according to the compound of embodiment 167, wherein

G ²Be furyl, thienyl, thiophenyl, pyrryl, imidazolyl, pyrazolyl, triazolyl, tetrazyl, thiazolyl, _ the azoles base, different _ the azoles base, _ di azoly, thiadiazolyl group, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl, indyl or indazolyl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as enforcement mode 1.

Embodiment 169: according to the compound of any embodiment 1 to 168, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other

Halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵,-OC (O) R ⁵⁴,-C (O) R ⁵⁴With-C (O) OR ⁵⁴, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 170: according to the compound of embodiment 169, wherein

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively, and alternatively by one or more C _1-6-alkyl replaces.

Embodiment 171: according to the compound of embodiment 170, wherein

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 172: according to the compound of embodiment 169, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 173: according to the compound of embodiment 172, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _3-10-aryl-C _1-6-alkylidene group-or C _3-10-aryl.

Embodiment 174: according to the compound of embodiment 173, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 175: according to the compound of embodiment 174, wherein

R ⁵⁴Be hydrogen.

Embodiment 176: according to the compound of embodiment 174 or embodiment 175, wherein

R ⁵⁵Be hydrogen.

Embodiment 177: according to the compound of embodiment 169, wherein

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁶³) _u-(CHR ⁶⁴) _v-Z, wherein

U is 1 or 2;

V is 0,1 or 2;

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-C _3-10-aryl, hydroxyl, hydroxyl-C _1-6-alkyl, amino or amino-C _1-6-alkyl;

Z be hydrogen ,-C-O-R ⁶⁵,-C (O) O-R ⁶⁵,-CONR ⁶⁵R ⁶⁶, C _1-6-alkylamino or two (C _1-6-alkyl)-amino, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl;

Perhaps

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen.

Embodiment 178: according to the compound of embodiment 177, wherein

U is 1;

V is 0 or 1.

Embodiment 179: according to the compound of embodiment 177 or embodiment 178, wherein

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, hydroxyl, hydroxyl-C _1-6-alkyl, amino or amino-C _1-6-alkyl.

Embodiment 180: according to the compound of any embodiment 177 to 179, wherein

Z is-C-O-R ⁶⁵Or-C (O) O-R ⁶⁵, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 181: according to the compound of any embodiment 177 to 179, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen.

Embodiment 182: according to the compound of embodiment 181, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and an annular atoms is oxygen, and all the other annular atomses are carbon.

Embodiment 183: according to the compound of embodiment 181, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon.

Embodiment 184: according to the compound of any embodiment 181 to 183, wherein

Z is five or six-ring, and one of them annular atoms is nitrogen.

Embodiment 185: according to the compound of any embodiment 181 to 184, wherein

Nitrogen-atoms is the Z group and-(CHR ⁶³) _u-(CHR ⁶⁴) _vThe tie point of-group.

Embodiment 186: according to the compound of any embodiment 177 to 185, wherein

R ⁵⁵Be hydrogen.

Embodiment 187: according to the compound of any embodiment 166 to 169, wherein

G ²Be substituted basic R ⁴³Replace, wherein

R ⁴³Be halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵,-OC (O) R ⁵⁴,-C (O) R ⁵⁴Or-C (O) OR ⁵⁴, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 188: according to the compound of embodiment 187, wherein

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively, and alternatively by one or more C _1-6-alkyl replaces.

Embodiment 189: according to the compound of embodiment 188, wherein

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 190: according to the compound of embodiment 187, wherein

R ⁵⁴With ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 191: according to the compound of embodiment 190, wherein

R ⁵⁴With ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _3-10-aryl-C _1-6-alkylidene group-or C _3-10-aryl.

Embodiment 192: according to the compound of embodiment 191, wherein

R ⁵⁴With ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 193: according to the compound of embodiment 192, wherein

R ⁵⁴Be hydrogen.

Embodiment 194: according to the compound of embodiment 192 or embodiment 193, wherein

R ⁵⁵Be hydrogen.

Embodiment 195: according to the compound of embodiment 187, wherein

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁶³) _u-(CHR ⁶⁴) _v-Z, wherein

U is 1 or 2;

V is 0,1 or 2;

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-C _3-10-aryl, hydroxyl, hydroxyl-C _1-6-alkyl, amino or amino-C _1-6-alkyl;

Z be hydrogen ,-C-O-R ⁶⁵,-C (O) O-R ⁶⁵,-CONR ⁶⁵R ⁶⁶, C ^1-6-alkylamino or two (C ^1-6-alkyl)-amino, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl;

Perhaps

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen.

Embodiment 196: according to the compound of embodiment 195, wherein

U is 1;

V is 0 or 1.

Embodiment 197: according to the compound of embodiment 195 or embodiment 196, wherein

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, hydroxyl, hydroxyl-C _1-6-alkyl, amino or amino-C ^1-6-alkyl.

Embodiment 198: according to the compound of any embodiment 195 to 197, wherein

Z is-C-O-R ⁶⁵Or-C (O) O-R ⁶⁵, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 199: according to the compound of any embodiment 195 to 197, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen.

Embodiment 200: according to the compound of embodiment 199, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and an annular atoms is oxygen, and all the other annular atomses are carbon.

Embodiment 201: according to the compound of embodiment 199, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon.

Embodiment 202: according to the compound of any embodiment 199 to 201, wherein

Z is five or hexa-atomic unit, and one of them annular atoms is nitrogen.

Embodiment 203: according to the compound of any embodiment 199 to 202, wherein

Nitrogen-atoms is the Z group and-(CHR ⁶³) _u-(CHR ⁶⁴) _vThe tie point of-group.

Embodiment 204: according to the compound of any embodiment 195 to 203, wherein

R ⁵⁵Be hydrogen.

Embodiment 205: according to the compound of embodiment 187, wherein

R ⁴³Be-CH ₂C (O) OR ⁵⁴, wherein

R ⁵⁴Be defined as enforcement mode 1.

Embodiment 206: according to the compound of embodiment 205, wherein

R ⁵⁴Be hydrogen, C _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 207: according to the compound of embodiment 206, wherein

R ⁵⁴Be hydrogen, C _1-6-alkyl, C _3-10-aryl-C _1-6-alkylidene group-or C _3-10-aryl.

Embodiment 208: according to the compound of embodiment 207, wherein

R ⁵⁴Be hydrogen or C _1-6-alkyl.

Embodiment 209: according to the compound of embodiment 208, wherein

R ⁵⁴Be hydrogen.

Embodiment 210: according to the compound of any embodiment 187 to 209, wherein

R ⁴³Be connected in the atom place adjacent with nitrogen-atoms, described nitrogen-atoms be connected G ²With-N (R ¹)-atom adjacent.

Embodiment 211: according to the compound of any embodiment 166 to 210, wherein

G ²Be

Or

Wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be hydrogen or defined as enforcement mode 1 independently of one another.Embodiment 212: according to the compound of embodiment 211, wherein

G ²Be

Or

Wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be hydrogen or defined as enforcement mode 1 independently of one another.

Embodiment 213: according to the compound of embodiment 211 or embodiment 212, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other hydrogen, halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵,-OC (O) R ⁵⁴,-C (O) R ⁵⁴With-C (O) OR ⁵⁴, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 214: according to the compound of embodiment 213, wherein

R ⁴³Be halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵,-OC (O) R ⁵⁴,-C (O) R ⁵⁴Or-C (O) OR ⁵⁴, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 215: according to the compound of embodiment 213 or 214, wherein

R ⁴³Be-C (O) OR ⁵⁴,-CH ₂C (O) OR ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵Or-CH ₂C (O) NR ⁵⁴R ⁵⁵, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 216: according to the compound of embodiment 214 or 215, wherein

R ⁴⁴Be alkyl or hydrogen.

Embodiment 217: according to the compound of embodiment 216, wherein

R ⁴⁴Be C _1-6-alkyl or hydrogen.

Embodiment 218: according to the compound of embodiment 217, wherein

R ⁴⁴Be hydrogen.

Embodiment 219: according to the compound of embodiment 213, wherein

R ⁴⁴Be halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₂,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵,-OC (O) R ⁵⁴,-C (O) R ⁵⁴Or-C (O) OR ⁵⁴, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 220: according to the compound of embodiment 213 or embodiment 219, wherein

R ⁴⁴Be-C (O) OR ⁵⁴,-CH ₂C (O) OR ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵Or-CH ₂C (O) NR ⁵⁴R ⁵⁵, wherein

R ⁵⁴And R ⁵⁵Be defined as enforcement mode 1.

Embodiment 221: according to the compound of embodiment 219 or 220, wherein

R ⁴³Be alkyl or hydrogen.

Embodiment 222: according to the compound of embodiment 221, wherein

R ⁴³Be C _1-6-alkyl or hydrogen.

Embodiment 223: according to the compound of embodiment 222, wherein

R ⁴³Be hydrogen.

Embodiment 224: according to the compound of any embodiment 211 to 213, wherein

R ⁴⁵Be hydrogen.

Embodiment 225: according to the compound of any embodiment 211 to 224, wherein

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively, and alternatively by one or more C _1-6-alkyl replaces.

Embodiment 226: according to the compound of embodiment 225, wherein

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment 227: according to the compound of any embodiment 211 to 224, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 228: according to the compound of any embodiment 211 to 224, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment 229: according to the compound of embodiment 228, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 230: according to the compound of embodiment 229, wherein

R ⁵⁴Be hydrogen.

Embodiment 231: according to the compound of any embodiment 211 to 230, wherein

R ⁵⁵Be hydrogen.

Embodiment 232: according to the compound of any embodiment 211 to 224, wherein

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁶³) _u-(CHR ⁶⁴) _v-Z, wherein

U is 1 or 2;

V is 0,1 or 2;

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-C _3-10-aryl, hydroxyl, hydroxyl-C _1-6-alkyl, amino or amino-C _1-6-alkyl;

Z be hydrogen ,-C-O-R ⁶⁵,-C (O) O-R ⁶⁵,-CONR ⁶⁵R ⁶⁶, C _1-6-alkylamino or two (C _1-6-alkyl)-amino, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl;

Perhaps

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen.

Embodiment 233: according to the compound of embodiment 232, wherein

U is 1;

V is 0 or 1.

Embodiment 234: according to the compound of embodiment 232 or embodiment 233, wherein

R ⁶³And R ⁶⁴Be hydrogen, C independently of one another _1-6-alkyl, hydroxyl, hydroxyl-C _1-6-alkyl, amino or amino-C _1-6-alkyl.

Embodiment 235: according to the compound of any embodiment 232 to 234, wherein

Z is-C-O-R ⁶⁵Or-C (O) O-R ⁶⁵, wherein

R ⁶⁵And R ⁶⁶Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment 236: according to the compound of any embodiment 232 to 234, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen.

Embodiment 237: according to the compound of embodiment 236, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and an annular atoms is oxygen, and all the other annular atomses are carbon.

Embodiment 238: according to the compound of embodiment 236, wherein

Z is five or six-ring, and wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon.

Embodiment 239: according to the compound of any embodiment 236 to 238, wherein

Z is five or six-ring, and one of them annular atoms is nitrogen.

Embodiment 240: according to the compound of any embodiment 236 to 239, wherein

Nitrogen-atoms is the Z group and-(CHR ⁶³) _u-(CHR ⁶⁴) _vThe tie point of-group.

Embodiment 241: according to the compound of any embodiment 195 to 240, wherein

R ⁵⁵Be hydrogen.

Embodiment 242: according to the compound of embodiment 213, wherein

R ⁴⁴Be hydrogen.

Embodiment 243: according to the compound of embodiment 213 or embodiment 242, wherein

R ⁴³Be hydrogen.

Embodiment 244: according to the compound of embodiment 242 or embodiment 243, wherein

R ⁴⁵Be hydrogen.

Embodiment 245: according to the compound of embodiment 1, it is

N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl]-N '-(thiazol-2-yl) sulphonamide,

1-(2-Phenoxyphenyl)-5-(thiazol-2-yl) biuret,

2-[([[(2-phenoxybenzamine base) alkylsulfonyl] amino] carbonyl) amino] thiazole,

N-(2-thiophenyl phenyl)-N '-(thiazol-2-yl) urea,

N-(2-benzenesulfonyl phenyl)-N '-(thiazol-2-yl) urea,

N-(2-benzyl phenyl)-N '-(thiazol-2-yl) urea,

N-(2-benzoyl phenyl)-N '-(thiazol-2-yl) urea,

N-[2-(phenyl amino) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-fluoro-6-(4-methoxyl group phenoxy group) benzyl]-N '-(thiazol-2-yl) urea,

N-(2-benzyloxy phenyl)-N '-(thiazol-2-yl) urea,

N-[2-(2,3,4-trimethoxy benzyloxy) phenyl]-N '-(thiazol-2-yl) urea,

N-(2-ethoxyl phenenyl)-N '-(thiazol-2-yl) urea,

N-(2-Phenoxyphenyl)-N '-(pyridine-2-yl) urea,

N-(2-Phenoxyphenyl)-N '-[(4-methoxycarbonyl methyl) thiazol-2-yl] urea,

N-methyl-N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea,

N-sec.-propyl-N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea,

N-[2-(4-methoxyl group phenoxy group) phenyl)-N '-(thiazol-2-yl) urea,

N-[2-(4-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-chlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-cyano-benzene oxygen) phenyl]-N '-thiazolyl urea,

N-[2-(4-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-sec.-propyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3,4-, two fluorophenoxies) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3,4-dichlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-chloro-3-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3,4-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3,4-methylenedioxybenzenes oxygen base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4 dichloro benzene oxygen base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4 difluorobenzene oxygen base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-fluoro-2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-methoxyl group-2-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-isopropoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methylthio group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methylsulfonyl phenoxy group) phenyl]-N '-thiazolyl urea,

N-[2-(2-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,6-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,6-, two fluorophenoxies) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methoxyl group-6-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[(3-methoxyl group-2-methoxycarbonyl phenoxy group) phenyl]-N ' (thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3,4-Trichlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4,6-trifluoromethoxy phenoxy base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4-dichloronaphtalene-1-oxygen base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methoxyl group phenoxy group)-5-(methylsulfonyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[5-cyano group-2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[5-fluoro-2-(2-methylthio group phenoxy group) phenyl]-N '-thiazolyl urea,

N-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl]-N ' (thiazol-2-yl) urea,

N-[2-(3,4-, two fluorophenoxies)-5-fluorophenyl]-N '-(thiazol-2-yl) urea,

N-[5-fluoro-2-(4-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4 dichloro benzene oxygen base)-5-fluorophenyl]-N '-(thiazol-2-yl) urea,

N-[5-fluoro-2-(4-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[5-fluoro-2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[5-fluoro-2-(2-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea,

N-[5-fluoro-2-(naphthalene-2-oxygen base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group)-6-fluorophenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-fluoro-2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group)-4-fluorophenyl]-N '-(thiazol-2-yl) urea,

N-[4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-fluoro-6-methoxyl group phenoxy group)-4-p-methoxy-phenyl]-N '-(thiazol-2-yl) urea,

N-[3-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group)-5-p-methoxy-phenyl]-N '-thiazol-2-yl urea,

N-[2-(2,3-dimethoxy phenoxy group)-4-aminomethyl phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group)-3-aminomethyl phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-chlorophenoxy)-5-chloro-phenyl-]-N '-(thiazol-2-yl) urea,

N-[5-chloro-2-(4-chloro-3-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(4-chlorophenoxy)-5-(trifluoromethyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[4,5-two fluoro-2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[4,5-two chloro-2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea,

N-[5-chloro-2-(2,3-dimethoxy phenoxy group)-4-dimethylamino phenyl]-N '-(thiazol-2-yl) urea,

N-[5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(4-morpholino base) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4 difluorobenzene oxygen base) pyridin-3-yl]-N '-(thiazol-2-yl) urea,

N-[2-(2-fluorophenoxy) pyridin-3-yl]-N '-[thiazol-2-yl] urea,

N-[2-(2-methoxyl group phenoxy group) pyridin-3-yl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dimethoxy phenoxy group) pyridin-3-yl]-N-(thiazol-2-yl) urea,

N-[4-chloro-2-(2-chlorobenzene formacyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[4-chloro-2-(2-fluoro benzoyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,4 difluorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea,

1-[2-(2-fluorobenzene sulfenyl) phenyl]-3-(thiazol-2-yl) urea,

N-[2-(2-chloro-4-fluorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2,3-dichlorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3,5-dimethyl benzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methoxycarbonyl thiophenyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-anisole sulfenyl) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-pyridine sulfenyl) phenyl]-N '-(thiazol-2-yl) urea,

N-(2-propoxy-phenyl)-N '-(thiazol-2-yl) urea,

N-(2-butoxy phenyl)-N '-(thiazol-2-yl) urea,

N-(2-(cyclopentyloxy phenyl)-N '-(thiazol-2-yl) urea,

N-(2-isopropyl phenyl)-N '-(thiazol-2-yl) urea,

N-[2-(2-methyl propoxy-) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(cyclopentyl methoxyl group) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(3-pentyloxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-pentyloxy) phenyl]-N '-(thiazol-2-yl) urea,

N-[2-(2-methoxy ethoxy) phenyl]-N '-(thiazol-2-yl) urea,

(2-[3-(2-benzyl phenyl) urea groups] thiazole-4-yl) acetic acid,

(2-[3-(2-benzoyl-4-chloro-phenyl-) urea groups] thiazole-4-yl) acetic acid,

(2-[3-(2-(2-methylphenoxy) phenyl) urea groups] thiazole-4-yl) acetic acid,

(2-[3-(2-(4-methoxyl group phenoxy group)-5-(trifluoromethyl) phenyl) urea groups] thiazole-4-yl) acetic acid,

2-[3-(2-Phenoxyphenyl) urea groups] and thiazole-4-yl } acetic acid,

2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carboxylic acid,

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's ethyl ester,

(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) the acetic acid ethyl ester,

(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) acetic acid,

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid,

(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) acetic acid,

2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-4-methylthiazol-5-carboxylic acid ethyl ester,

2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-4-methylthiazol-5-carboxylic acid,

N-ethyl-2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) ethanamide,

2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl)-N-(2-methoxyl group-ethyl) ethanamide,

2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl)-N-(2-morpholine-4-base ethyl) ethanamide,

[2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) kharophen] the acetic acid methyl ester,

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's (2-methoxy ethyl) acid amides,

[2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) kharophen] acetic acid,

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's buserelin,

[(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carbonyl) amino] the acetic acid methyl ester,

(5-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-[1,3,4] thiadiazoles-2-yl) the acetic acid ethyl ester,

[(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carbonyl) amino] acetic acid,

(5-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-[1,3,4] thiadiazoles-2-yl) acetic acid,

5-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups }-[1,3,4] thiadiazoles-2-carboxylic acid ethyl ester,

(5-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups }-[1,3,4] thiadiazoles-2-yl) the acetic acid ethyl ester,

3-[2-(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) kharophen] the propionic acid methyl ester,

2-(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl)-N-(2-morpholine-4-base ethyl) ethanamide,

[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino] the acetic acid methyl ester,

3-[2-(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) kharophen] propionic acid,

[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino] acetic acid,

(R) 3-[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino]-2-hydroxyl-propionic acid,

2-[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino]-3-hydroxyl-propionic acid,

1-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-3-thiazol-2-yl-urea,

1-(2-isobutyryl-4-aminomethyl phenyl)-3-thiazol-2-yl-urea,

1-[5-fluoro-2-(3-methylbutyryl base) phenyl]-3-thiazol-2-yl-urea,

1-[5-methyl-2-(3-methylbutyryl base) phenyl]-3-thiazol-2-yl-urea,

[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid ethyl ester,

[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid,

2-[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl]-the N-methylacetamide,

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester,

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } acetic acid,

{ 3-pentamethylene carbonyl-4-{3-(4-ethoxycarbonylmethyl group thiazol-2-yl)-urea groups } phenyl } the acetic acid ethyl ester,

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea,

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxylic acid's ethyl ester,

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxylic acid,

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxamide,

2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-ethanamide,

2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide,

4-(2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-ethanoyl)-1-methyl-piperazine _ chlorine,

1-[4-methyl-2-(2-methyl propoxy-) phenyl]-3-thiazol-2-yl-urea,

2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid, perhaps

2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide.

Embodiment 246: according to the compound of any embodiment 1 to 245, when testing under the glucose concn at 2mM, in glucokinase activation determination method disclosed herein (I), this compound is the activator of glucokinase.

Embodiment 247: according to the compound of any embodiment 1 to 246, when when testing under 10 to 15mM the glucose concn, in glucokinase activation determination method disclosed herein (I), this compound is the activator of glucokinase.

Embodiment 248: according to the compound of any embodiment 1 to 247, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the concentration of 30 μ M.

Embodiment 249: according to the compound of any embodiment 1 to 248, under 10 to 15mM the glucose concn, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the concentration of 30 μ M.

Embodiment 250: according to the compound of any embodiment 1 to 249, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the concentration of 5 μ M.

Embodiment 251: according to the compound of any embodiment 1 to 250, under 10 to 15mM the glucose concn, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the concentration of 5 μ M.

Embodiment 252: a kind of glucokinase activators compound, it is defined as a kind of like this compound, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound is producing under the glucose concn of glucokinase specific activity at 2mM, when not having compound in glucokinase activation determination method (I) measured highly 1.5 times under 30 μ M or the following concentration, wherein the increase of the glucokinase activity that is provided by this compound reduces and increases along with glucose concn.

Embodiment 253: according to the compound of any embodiment 1 to 251, this compound provides the increase of glucokinase activity, and wherein the increase of the glucokinase activity that is provided by this compound reduces and increases along with glucose concn.

Embodiment 254: according to the compound of embodiment 252 or embodiment 253, under the glucose concn of 5mM, in glucokinase activation determination method disclosed herein (I), this compound provides the increase of glucokinase activity, and wherein this increase is significantly higher than in the active increase of the glucokinase that is provided by this compound under the glucose concn of 15mM, in glucokinase activation determination method disclosed herein (I).

Embodiment 255: according to the compound of any embodiment 252 to 254, under the glucose concn of 5mM, in glucokinase activation determination method disclosed herein (I), this compound provides the increase of glucokinase activity under the compound concentration of 10 μ M, wherein this increase is significantly higher than in the active increase of the glucokinase that is provided under the compound concentration of 10 μ M by this compound under the glucose concn of 15mM, in glucokinase activation determination method disclosed herein (I).

Embodiment 256: according to the compound of any embodiment 252 to 255, under the glucose concn of 5mM, in glucokinase activation determination method disclosed herein (I), this compound provides the increase of glucokinase activity under the compound concentration of 10 μ M, this increases than under the glucose concn of 15mM, at least 1.1 times of the increase height of the glucokinase activity that in glucokinase activation determination method disclosed herein (I), is provided under the compound concentration of 10 μ M by this compound, for example at least 1.2 times, for example at least 1.3 times, for example at least 1.4 times, for example at least 1.5 times, for example at least 1.6 times, for example at least 1.7 times, for example at least 1.8 times, for example at least 1.9 times, for example at least 2.0 times.

Embodiment 257: a kind of glucokinase activators compound, it is defined as a kind of like this compound, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound is measured high 1.5 times under the glucose concn of glucokinase specific activity at 2mM that produces under 30 μ M or the lower compound concentration, when not having compound in glucokinase activation determination method (I), this glucokinase activators compound increases the glucose utilization in the liver, and does not induce insulin secretion in response to glucose any increase to be arranged.

Embodiment 258: a kind of glucokinase activators compound, it is defined as a kind of like this compound, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound is measured high 1.5 times under the glucose concn of glucokinase specific activity at 2mM that produces under 30 μ M or the lower compound concentration, when not having compound in glucokinase activation determination method (I), this glucokinase activators compound in the liver cell that separates than in the Ins-1 cell, showing significantly higher activity.

Embodiment 259: according to the compound of any embodiment 1 to 256, this compound increases the glucose utilization in the liver, and does not induce insulin secretion in response to glucose any increase to be arranged.

Embodiment 260: according to the compound of any embodiment 1 to 256, this compound ratio in the liver cell that separates shows significantly higher activity in the Ins-1 cell.

Embodiment 261: according to the compound of any embodiment 257 to 260, this compound when measurement as described in glucokinase activation measurement (II) in the liver cell that separates than when as glucokinase activation measurement (III) described in, measuring, in the Ins-1 cell, showing remarkable higher activity.

Embodiment 262: according to the compound of embodiment 261, this compound shows active when measurement as described in glucokinase activation measurement (II) in the liver cell that separates, this compound of this specific activity at least 1.1 times of active height in the Ins-1 cell when described in glucokinase activation measurement (III), measuring, for example at least 1.2 times, for example at least 1.3 times, for example at least 1.4 times, for example at least 1.5 times, for example at least 1.6 times, for example at least 1.7 times, for example at least 1.8 times, for example at least 1.9 times, for example at least 2.0 times, for example at least 3.0 times, for example at least 4.0 times, for example at least 5.0 times, for example at least 10 times.

Embodiment 263: according to the compound of embodiment 261, this compound shows in the Ins-1 cell when measurement as described in glucokinase activation measurement (III) does not have activity.

Embodiment 264: the compound any according to embodiment 1 to 263, it is the medicine that can be used for treating the indication that is selected from down group: hyperglycemia, IGT, insulin resistance syndrome, X syndrome, diabetes B, type 1 diabetes, hyperlipemia, hypertension and obesity.

Embodiment 265: according to the purposes of any one compound of embodiment 1 to 264 as medicine.

Embodiment 266: the compound any according to embodiment 1 to 264 is used for the treatment of the secretion that hyperglycemia, treatment IGT, treatment X syndrome, treatment diabetes B, treatment type 1 diabetes, treatment hyperlipemia, treatment hyperlipemia, treatment hypertension, treatment are fat, reduce ingestion of food, be used for appetite stimulator, be used for regulating feeding behavior or be used for strengthening incretin (enteroincretins), for example GLP-1.

On the other hand, the present invention provides general formula (I) compound in embodiment A1

A ¹Be selected from the group of being formed by arylidene, inferior heteroaryl, fused rings alkyl arylidene, annelated heterocycles base arylidene, fused rings alkyl inferior heteroaryl or annelated heterocycles base inferior heteroaryl;

It is alternatively by one or more substituent R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-C (O) R ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-C _1-6-alkylidene group-Z-, R ⁶-W ¹-C _1-6-arylidene-Z-, R ⁶-W ¹-inferior heteroaryl-Z-, R ⁶-W ¹-Ya heterocyclic radical-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z, R ⁶-W ¹-C _1-6-alkylidene group-Z-, heterocyclic radical-Z-C _1-6-alkylidene group-, heterocyclic radical-C _1-6-alkylidene group-Z-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-Z-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-arylidene-Z-, heterocyclic radical-arylidene-Z-, C _3-10-cyclic hydrocarbon radical-inferior heteroaryl-Z-, heterocyclic radical-inferior heteroaryl-Z-, aryl-C _3-10-Ya cyclic hydrocarbon radical-Z-, aryl-Ya heterocyclic radical-Z-, heteroaryl-C _3-10-Ya cyclic hydrocarbon radical-Z-, heteroaryl-Ya heterocyclic radical-Z-, heterocyclic radical-C _3-10-Ya cyclic hydrocarbon radical-Z-, aryl-inferior heteroaryl-Z-, heteroaryl-arylidene-Z-, aryl-arylidene-Z-, heteroaryl-inferior heteroaryl-Z-,

Wherein arbitrarily monovalence or divalence C _1-6-alkyl, C _3-10-cyclic hydrocarbon radical, heterocyclic radical, aryl or heteroaryl moieties can be alternatively by one or more R that independently are selected from ²Substituting group replace, wherein

R ²And R ³Be independently of one another hydrogen, halogen, hydroxyl ,-CN ,-CF ₃,-OCF ₃,-NO ₂,-C (O) OH ,-NH ₂, C _1-6-alkyl, C _1-6-alkoxyl group, aryloxy, R ⁶-Z-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl;

Perhaps

R ²And R ³When being connected with same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively;

Z and W ¹Be independently of one another direct key ,-O-,-N (R ⁷)-,-N (R ⁷) C (R ⁷R ⁸)-,-S-,-SO ₂-,-C (O) N (R ⁷)-,-N (R ⁷) C (O)-,-N (R ⁷) C (O) C (R ⁷R ⁸)-,-N (R ⁷) CON (R ⁸)-,-N (R ⁷) SO ₂-,-SO ₂N (R ⁷)-,-C (O)-,-C (O)-O-,-N (R ⁷) SO ₂N (R ⁸)-or-O-C (O)-, wherein

R ⁷And R ⁸Be hydrogen or C independently of one another under every kind of individual cases _1-6-alkyl;

R ⁴, R ⁵And R ⁶Be independently from each other by hydrogen, cyano group, halogen, aryl, heteroaryl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical, optional by one or more C _1-6The heterocyclic radical that-alkyl replaces or alternatively by halogen ,-S (O) ₂CH ₃Or the C of COOH replacement _1-6The group that-alkyl is formed;

Perhaps

R ⁴And R ⁵Can constitute together and have formula-(CH ₂) _j-Q-(CH ₂) _k-ring, it is bonded to R ⁴And R ⁵The nitrogen-atoms place that connects, wherein

J and k are 1,2,3 or 4 independently of one another;

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be independently from each other by hydrogen, aryl, C _1-6The group of-alkyl and aryl-alkylidene group-composition;

L ¹Be key ,-D-C _1-6-alkylidene group-E-,-D-C _2-6-alkenylene-E-,-D-C _2-6-alkynylene-E-,-the inferior cyclic hydrocarbon radical-E-of D-,-the inferior heterocyclic radical-E-of D-,-O-,-S-,-S (O)-,-S (O) ₂-,-C (O)-,-N (R ¹¹)-or-C (=N-OR ¹²)-, wherein

D and E be independently of one another direct key ,-O-or-S-;

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-O-C (O)-, aryl-C _1-6-alkylidene group-O-C (O)-, heteroaryl-C _1-6-alkylidene group-O-C (O)-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, heteroaryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, heteroaryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, heteroaryl-SO ₂-, C _1-6-alkyl-NH-SO ₂-, aryl-C _1-6-alkylidene group-NH-SO ₂-, heteroaryl-C _1-6-alkylidene group-NH-SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, heteroaryl-C _1-6-alkylidene group-C (O)-, C _1-6-alkyl-Y-, aryl-Y-, heteroaryl-Y-, aryl-C _1-6-alkylidene group-Y-, heteroaryl-C _1-6-alkylidene group-Y-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, heteroaryl, C _1-6-alkyl, C _1-6-alkoxyl group, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkoxyl group-, heteroaryl-C _1-6-alkoxyl group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-inferior heteroaryl-or C _1-6-alkoxyl group-arylidene-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, it is bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-CON (H)-,-NHC (O)-,-NHCON (H)-,-NHSO ₂-,-SO ₂N (H)-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ¹⁶And R ¹⁷Be selected from hydrogen, aryl, heteroaryl, C _1-6-alkyl, C _1-6-alkoxyl group, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-arylidene-, C _1-6-alkoxyl group-inferior heteroaryl-, heteroaryl aryl-C _1-6-alkoxyl group-or aryl-C _1-6-alkoxyl group-;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-or aryl-C _1-6The group of-alkylidene group-composition;

R ¹²Be selected from hydrogen, aryl, heteroaryl, C _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-inferior heteroaryl-or C _1-6-alkoxyl group-arylidene-;

G ¹Be C _1-6-alkyl, C _3-10-cyclic hydrocarbon radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _2-6-thiazolinyl or C _2-6-alkynyl, they all can be replaced by one or more substituting groups alternatively, described substituting group be independently selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹, C _3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl;

Perhaps

R ¹⁸And R ¹⁹When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively;

Perhaps

G ¹Be aryl, heteroaryl, heterocyclic radical, fused rings alkyl heteroaryl, annelated heterocycles Ji Fangji, fused-aryl heterocyclic radical or fused rings alkylaryl, they all can be alternatively by one or more R that are selected from ⁴⁰, R ⁴¹And R ⁴²Substituting group replace;

L ²Be direct key, C _1-6-alkylidene group, C _2-6-alkenylene, C _2-6-alkynylene ,-N (R ²⁰)-,-C _1-6-alkylidene group-N (R ²⁰)-,-C _2-6-alkenylene-N (R ²⁰)-,-C _2-6-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be hydrogen, perhaps

R ²⁰Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, cyclic hydrocarbon radical-W ³, heterocyclic radical-W ³-, aryl-W ³-, heteroaryl-W ³-, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

W ³Be C _1-6-alkylidene group or direct key;

L wherein ¹And L ²Be connected A ¹In adjacent atom place;

L ³Be-C (O)-,-C (O)-C (O)-,-C (O) CH ₂C (O)-or-S (O) ₂-;

R ¹Be hydrogen, perhaps

R ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, cyclic hydrocarbon radical-W ⁴, heterocyclic radical-W ⁴, aryl-W ⁴-or heteroaryl-W ⁴-,

Alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

W ⁴Be C _1-6-alkylidene group or direct key;

G ²Be heteroaryl, annelated heterocycles base heteroaryl or fused rings alkyl heteroaryl,

Alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possesses and is connected described heteroaryl and-N (R ¹)-the adjacent nitrogen-atoms of atom;

Perhaps following formula group

Or

Wherein

G ³And G ⁵Be C independently of one another _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, cyclic hydrocarbon radical-R ²²-, heterocyclic radical-R ²²-, aryl-R ²²-, heteroaryl-R ²²-,

Alternatively by one or more substituent R ⁴⁶, R ⁴⁷And R ⁴⁸Replace, wherein

R ²²Be alkylidene group or direct key;

R ²¹Be hydrogen, C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, cyclic hydrocarbon radical-W ⁵-or heterocyclic radical-W ⁵-,

Alternatively by one or more substituent R ³⁶, R ³⁷And R ³⁸Replace, perhaps

R ²¹Be aryl-W ⁵-or heteroaryl-W ⁵, it is alternatively by one or more substituent R ⁴⁹, R ⁵⁰And R ⁵¹Replace, wherein

W ⁵Be C _1-6-alkylidene group or direct key;

Wherein

R ³⁰, R ³¹, R ³², R ³³, R ³⁴, R ³⁵, R ³⁶, R ³⁷And R ³⁸Be independently from each other-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵²,-NR ⁵²R ⁵³,-SR ⁵²,-NR ⁵²S (O) ₂R ⁵³,-S (O) ₂NR ⁵²R ⁵³,-S (O) NR ⁵²R ⁵³,-S (O) R ⁵²,-S (O) ₂R ⁵²,-C (O) NR ⁵²R ⁵³,-OC (O) NR ⁵²R ⁵³,-NR ⁵²C (O) R ⁵³,-CH ₂C (O) NR ⁵²R ⁵³,-OCH ₂C (O) NR ⁵²R ⁵³,-CH ₂OR ⁵²,-CH ₂NR ⁵²R ⁵³,-OC (O) R ⁵²,-C (O) R ⁵²With-C (O) OR ⁵²Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵²,-NR ⁵²R ⁵³And C _1-6-alkyl; Perhaps

C _3-10-cyclic hydrocarbon radical, C _4-8-cycloalkenyl group, heterocyclic radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylthio-, C _3-10-cyclic hydrocarbon sulfenyl, C _3-10-cyclic hydrocarbon radical-C _2-6-alkenylene-, C _3-10-cyclic hydrocarbon radical-C _2-6-alkynylene-, C _4-8-cycloalkenyl group-C _1-6-alkylidene group-, C _4-8-cycloalkenyl group-C _2-6-alkenylene-, C _4-8-cycloalkenyl group-C _2-6-alkynylene-, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical-C _2-6-alkenylene-, heterocyclic radical-C _2-6-alkynylene-, aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, aryl-C _2-6-alkenylene-, aryl-C _2-6-alkynylene-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, heteroaryl-C _2-6-alkenylene-and heteroaryl-C _2-6-alkynylene-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵²,-NR ⁵²R ⁵³And C _1-6-alkyl, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-heteroaryl-C _1-6-alkylidene group-heteroaryl or aryl;

Perhaps

R ⁵²And R ⁵³When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively;

R ⁴⁰, R ⁴¹, R ⁴², R ⁴³, R ⁴⁴, R ⁴⁵, R ⁴⁶, R ⁴⁷, R ⁴⁸, R ⁴⁹, R ⁵⁰And R ⁵¹Be independently of one another-CN ,-NO ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵, halogen ,-S-C _1-6-alkylidene group-OR ⁵⁴,-S (O) ₂-C _1-6-alkylidene group-OR ⁵⁴,-C _1-6-alkylidene group-S-R ⁵⁴,-C _1-6-alkylidene group-S (O) R ⁵⁴,-C _1-6-alkylidene group-S (O) ₂R ⁵⁴,-C _1-6-alkylidene group-N (R ⁵⁴) S (O) ₂R ⁵⁵,-N (R ⁵⁴) S (O) ₂R ⁵⁵,-C _1-6-alkylidene group-CN ,-C _1-6-alkylidene group-C (O) NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) R ⁵⁵,-N (R ⁵⁴) C (O) R ⁵⁵,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) NR ⁵⁵R ⁵⁶,-C _1-6-alkylidene group-NHC (=NR ⁵⁴) NR ⁵⁵R ⁵⁶,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) OR ⁵⁵,-N (R ⁵⁴) C (O) OR ⁵⁵,-C _1-6-alkylidene group-C (O) OR ⁵⁴,-C _1-6-alkylidene group-N (R ⁵⁴) S (O) ₂R ⁵⁵,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-O (CH ₂) _1-3OR ⁵⁴,-C _1-6-alkylidene group-O-R ⁵⁴,-C _1-6-alkylidene group-C (O) R ⁵⁴,-C _1-6-alkylidene group-NR ⁵⁴R ⁵⁵,-C (=NR ⁵⁴)-O-R ⁵⁵,-C (=N (OR ⁵⁴)) C (O) OR ⁵⁵,-C (=N (OR ⁵⁴)) C (O) R ⁵⁵,-C _1-6-alkylidene group-C (=N (OR ⁵⁴)) C (O) ⁵⁵,-C _1-6-alkylidene group=N-O-R ⁵⁴,-C _1-6-alkylidene group-N (R ⁵⁴) S (O) ₂NR ⁵⁵R ⁵⁶,-N (R ⁵⁴) S (O) ₂NR ⁵⁵R ⁵⁴,-N (R ⁵⁴) S (O) ₂NR ⁵⁵R ⁵⁶,-OC (O) R ⁵⁴,-C _1-6-alkylidene group-C (O) N (R ⁵⁴) S (O) ₂R ⁵⁵,-C (O) N (R ⁵⁴) S (O) ₂R ⁵⁵,-C _1-6-alkylidene group-C (R ⁵⁴)=N-OR ⁵⁵,-NHC (=NR ⁵⁴) NR ⁵⁵R ⁵⁶,-G _1-6-alkylidene group-NHC (=NR ⁵⁴) NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group-N=C (N (R ⁵⁴R ⁵⁵)) ₂,-N=C (N (R ⁵⁴R ⁵⁵)) ₂,-C (O) R ⁵⁴With-C (O) OR ⁵⁴Perhaps

C _1-6-alkyl, C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups separately alternatively, and described substituting group is independently selected from halogen, R ⁵⁴,-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-C (O) OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl; Perhaps

C _3-10-cyclic hydrocarbon radical, C _4-8-cycloalkenyl group, heterocyclic radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylthio-, C _3-10-cyclic hydrocarbon sulfenyl, C _3-10-cyclic hydrocarbon radical-C _2-6-alkenylene-, C _3-10-cyclic hydrocarbon radical-C _2-6-alkynylene-, C _4-8-cycloalkenyl group-C _1-6-alkylidene group-, C _4-8-cycloalkenyl group-C _2-6-alkenylene-, C _4-8-cycloalkenyl group-C _2-6-alkynylene-, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical-C _2-6-alkenylene-, heterocyclic radical-C _2-6-alkynylene-, heterocyclic radical part wherein alternatively can be by one or more R that independently are selected from ⁷⁰Substituting group replace; Perhaps

Aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, aryl-C _2-6-alkenylene-, aryl-C _2-6-alkynylene-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, heteroaryl-S-C _1-6-alkylidene group-, heteroaryl-C _2-6-alkenylene-and heteroaryl-C _2-6-alkynylene-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, C independently of one another _1-6-alkyl ,-Si (C _1-6-alkyl) ₃, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heterocyclic radical, heterocyclic radical-C _1-6-alkylidene group-, heteroaryl or aryl, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace;

Perhaps

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁷²) _u-(CHR ⁷³) _x-W ⁶, wherein

U is 0,1 or 2;

V is 0,1 or 2;

R ⁷²And R ⁷³Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-aryl, hydroxyl, hydroxyalkyl ,-C (O) O-R ⁷⁵, amino or aminoalkyl group;

W ⁶Be hydrogen ,-O-R ⁷⁵,-C (O) O-R ⁷⁵,-C (O)-R ⁷⁵,-CONR ⁷⁵R ⁷⁶,-NR ⁷⁵R ⁷⁶,-NHCH ₂C (O) R ⁷⁵,-NHC (O) R ⁷⁵,-NHC (O) OR ⁷⁵,-S (O) ₂R ⁷⁵,-NHS (O) ₂R ⁷⁵, alkylamino or dialkyl amido, perhaps

W ⁶Be five or six-ring, wherein at least one annular atoms is nitrogen, and all the other annular atomses are carbon or oxygen, perhaps alternatively by C _1-6-alkyl ,-C (O) O-R ⁷⁵,-(CH ₂) _1-3C (O) O-R ⁷⁵,=O replaces;

Perhaps

W ⁶Be phthalimido or heterocyclic radical;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively, and alternatively by one or more C _1-6Alkyl replaces;

R ⁷⁰Be=O ,-C (O) CH ₃,-S (O) ₂CH ₃,-CF ₃,-C (O) O-R ⁷⁵,-(CH ₂) _1-3C (O) O-R ⁷⁵Or C _1-6-alkyl;

R ⁷¹Be=O, C _1-6-alkyl, cyclic hydrocarbon radical ,-C (O) O-R ⁷⁵,-(CH ₂) _1-3C (O) O-R ⁷⁵,-(CH ₂) _1-3NR ⁷⁵R ⁷⁶,-OH or amino;

R ⁷⁵And R ⁷⁶Be independently of one another hydrogen, halogen ,-OH ,-CF ₃Or optional quilt-NH ₂The C that replaces _1-6-alkyl;

Perhaps its pharmacy acceptable salt, solvate or prodrug.

Embodiment A2. is according to the compound of embodiment A1, wherein

A ¹Be arylidene or inferior heteroaryl, it is alternatively by one or more substituent R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-, heteroaryl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A3. is according to the compound of embodiment A2, wherein

A ¹Be C _6-10-arylidene or C _4-10-inferior heteroaryl, it is alternatively by one or more substituent R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-, heteroaryl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A4. is according to the compound of embodiment A3, wherein

A ¹Be phenylene, it is alternatively by one or more substituent R ²³, R ²⁴, R ^25,R ²⁶And R ²⁷Replace, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _2-6-thiazolinyl-Z-, C _2-6-alkynyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-, heteroaryl-Z-, aryl-C _1-6-alkylidene group-Z-, heteroaryl-C _1-6-alkylidene group-Z-, heterocyclic radical-C _1-6-alkylidene group-Z-, cyclic hydrocarbon radical-C _1-6-alkylidene group-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A5. is according to formula (Ia) compound of embodiment A4

L wherein ¹, G ¹, L ², L ³, R ¹, G ²And R ²⁵Be defined as implementing mode A1.

Embodiment A6. is according to formula (Ib) compound of embodiment A4

L wherein ¹, G ¹, L ², L ³, R ¹, G ²And R ²⁴Be defined as implementing mode A1.

The compound that embodiment A7. is any one according to embodiment A1 to A6, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A8. is according to the compound of embodiment A7, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-CN ,-CF ₃,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A9. is according to the compound of embodiment A8, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

Halogen ,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, R ⁶-W ¹-Z-and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A10. according to the compound of embodiment A9 wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷Be independently from each other the group of being formed by following groups:

F, Cl, Br and methyl.

The compound that embodiment A11. is any one according to embodiment A1 to A10, wherein

R ⁴, R ⁵And R ⁶Be independently from each other by hydrogen, aryl, C _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-and aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A12. is according to the compound of embodiment A11, wherein

R ⁴, R ⁵And R ⁶Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A13. is according to the compound of embodiment A12, wherein

R ⁴, R ⁵And R ⁶Be hydrogen.

The compound that embodiment A14. is any one according to embodiment A1 to A9, wherein

R ⁴And R ⁵Constitute together and have formula-(CH ₂) _j-Q-(CH ₂) _k-ring, it is bonded to R ⁴And R ⁵The nitrogen-atoms place that connects, wherein

J and k are 1,2,3 or 4 independently of one another;

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be independently from each other by hydrogen, aryl, C _1-6-alkyl and aryl-C _1-6The group of-alkyl-composition.

Embodiment A15. is according to the compound of embodiment A14, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A16. is according to the compound of embodiment A15, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Embodiment A17. is according to the compound of embodiment A16, and wherein Q is direct key.

The compound that embodiment A18. is any one according to embodiment A1 to A17, wherein

W ¹Be direct key ,-O-,-C (O)-,-NH-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment A19. is according to the compound of embodiment A18, wherein

W ¹Be direct key ,-O-,-C (O)-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) SO ₂-,-C (O)-O-or-O-C (O)-.

Embodiment A20. is according to the compound of embodiment A19, wherein W ¹Be direct key or-C (O)-O-.

Embodiment A21. is according to the compound of embodiment A20, wherein W ¹It is direct key.

Embodiment A22. is according to the compound of embodiment A7, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, wherein

R ², R ³With Z be defined as implementing mode A1.

Embodiment A23. is according to the compound of embodiment A22, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as implementing mode A1.

Embodiment A24. is according to the compound of embodiment A23, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as implementing mode A1.

Embodiment A25. is according to the compound of embodiment A24, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one to be F, Cl, Br or methyl.

Embodiment A26. is according to the compound of embodiment A24, wherein

R ²³, R ²⁴, R ²⁵, R ²⁶And R ²⁷In have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²Or-NR ²R ³, wherein

R ², R ³With Z be defined as implementing mode A1.

The compound that embodiment A27. is any one according to embodiment A1 to A26, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment A28. is according to the compound of embodiment A27, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment A29. is according to the compound of embodiment A28, wherein

R ²Be hydrogen or C _1-6-alkyl.

Embodiment A30. is according to the compound of embodiment A29, wherein

R ²Be hydrogen.

The compound that embodiment A31. is any one according to embodiment A1 to A30, wherein

R ³Be hydrogen or C _1-6-alkyl.

Embodiment A32. is according to the compound of embodiment A31, wherein

R ³Be hydrogen.

The compound that embodiment A33. is any one according to embodiment A1 to A22, wherein

R ²And R ³When with-when nitrogen-atoms is connected, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two pair keys alternatively.

The compound that embodiment A34. is any one according to embodiment A1 to A33, wherein

Z be direct key ,-O-,-NH-,-NHCH ₂-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (CH ₃) CONH-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment A35. is according to the compound of embodiment A34, wherein

Z be direct key ,-O-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) SO ₂-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment A36. is according to the compound of embodiment A35, wherein

Z be direct key ,-NHC (O)-or-NHS (O) ₂-.

Embodiment A37. is according to the compound of embodiment A2, wherein

A ¹Be

Wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Be hydrogen or defined as implementing mode A1 independently of one another.

Embodiment A38. is according to the compound of embodiment A37, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Be independently from each other the group of being formed by following groups:

Halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, N (R ⁴R ⁵)-C _1-6-alkylidene group-Z-, R ⁶-W ¹-Z-, R ⁶-W ¹-N (R ⁴)-Z-, R ⁶-N (R ⁴)-Z-and R ⁶-W ¹-C _1-6-alkylidene group-Z-, wherein

R ², R ³, R ⁴, R ⁵, R ⁶, Z and W ¹Be defined as implementing mode A1.

Embodiment A39. is according to the compound of embodiment A37 or A38, wherein

R ⁴, R ⁵And R ⁶Be independently from each other by hydrogen, aryl, C _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-and aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A40. is according to the compound of embodiment A39, wherein

R ⁴, R ⁵And R ⁶Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A41. is according to the compound of embodiment A40, wherein

R ⁴, R ⁵And R ⁶Be hydrogen.

Embodiment A42. is according to the compound of embodiment A37 or A38, wherein

R ⁴And R ⁵Constitute together and have formula-(CH ₂) _j-Q-(CH ₂) _k-ring, it is bonded to R ⁴And R ⁵The nitrogen-atoms place that connects, wherein

J and k are 1,2,3 or 4 independently of one another;

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be independently from each other by hydrogen, aryl, C _1-6The group of-alkyl and arylalkyl-composition.

Embodiment A43. is according to the compound of embodiment A42, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ⁹And R ¹⁰Be hydrogen or alkyl independently of one another.

Embodiment A44. is according to the compound of embodiment A43, wherein

Q be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-C (O) NH-,-NHC (O)-,-NHC (O) NH-,-NHSO ₂-,-SO ₂NH-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Embodiment A45. is according to the compound of embodiment A44, wherein

Q is direct key.

The compound that embodiment A46. is any one according to embodiment A37 to A45, wherein

W ¹Be direct key ,-O-,-C (O)-,-NH-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment A47. is according to the compound of embodiment A46, wherein

W ¹Be direct key ,-O-,-C (O)-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) SO ₂-,-C (O)-O-or-O-C (O)-.

Embodiment A48. is according to the compound of embodiment A47, wherein

W ¹Be direct key or-C (O)-O-.

Embodiment A49. is according to the compound of embodiment A48, wherein

W ¹It is direct key.

Embodiment A50. is according to the compound of embodiment A37, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, cyclic hydrocarbon radical-Z-, heterocyclic radical-Z-, aryl-Z-or heteroaryl-Z-, wherein

R ², R ³With Z be defined as implementing mode A37.

Embodiment A51. is according to the compound of embodiment A50, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least one be halogen ,-C (O) OR ²,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as implementing mode A37.

Embodiment A52. is according to the compound of embodiment A51, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, C _3-10-cyclic hydrocarbon radical-Z-, C _3-10-heterocyclic radical-Z-, C _3-10-aryl-Z-or C _3-10-heteroaryl-Z-, wherein

R ², R ³With Z be defined as implementing mode A37.

The compound that embodiment A53. is any one according to embodiment A37 to A52, wherein

Z be direct key ,-O-,-NH-,-NHCH ₂-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) CON (H)-,-N (CH ₃) CON (H)-,-N (H) SO ₂-,-SO ₂N (H)-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment A54. is according to the compound of embodiment A53, wherein

Z be direct key ,-O-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) SO ₂-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-.

Embodiment A55. is according to the compound of embodiment A54, wherein

Z be direct key ,-NHC (O)-or-NHS (O) ₂

Embodiment A56. is according to the compound of embodiment A52, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least one be halogen ,-C (O) OR ²,-CN ,-NO ₂,-OR ²,-NR ²R ³Or C _1-6-alkyl, wherein

R ²And R ³Be defined as implementing mode A37.

The compound that embodiment A57. is any one according to embodiment A37 to A56, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment A58. is according to the compound of embodiment A57, wherein

R ²And R ³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment A59. is according to the compound of embodiment A58, wherein

R ²Be hydrogen or C _1-6-alkyl.

Embodiment A60. is according to the compound of embodiment A59, wherein

R ²Be hydrogen.

The compound that embodiment A61. is any one according to embodiment A37 to A60, wherein

R ³Be hydrogen or C _1-6-alkyl.

Embodiment A62. is according to the compound of embodiment A61, wherein

R ³Be hydrogen.

The compound that embodiment A63. is any one according to embodiment A37 to A50, wherein

R ²And R ³When being connected with same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

The compound that embodiment A64. is any one according to embodiment A37 to A55, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least one to be hydrogen.

Embodiment A65. is according to the compound of embodiment A64, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least two to be hydrogen.

Embodiment A66. is according to the compound of embodiment A65, wherein

R ²³And R ²⁶Be hydrogen.

Embodiment A67. is according to the compound of embodiment A65 or embodiment A66,

Wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least three to be hydrogen.

The compound that embodiment A68. is any one according to embodiment A37 to A67, wherein R ²⁴Or R ²⁵It is halogen.

Embodiment A69. is according to the compound of embodiment A68, wherein R ²⁴Or R ²⁵It is fluorine.

The compound that embodiment A70. is any one according to embodiment A37 to A67, wherein R ²⁴Or R ²⁵Be C _1-6-alkyl.

Embodiment A71. is according to the compound of embodiment A68, wherein R ²⁴Or R ²⁵It is methyl.

The compound that embodiment A72. is any one according to embodiment A37 to A67, wherein

R ²⁴Be hydrogen.

The compound that embodiment A73. is any one according to embodiment A37 to A72, wherein

R ²⁵Be hydrogen.

Embodiment A74. is according to the compound of embodiment A37, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶Be hydrogen.

The compound that embodiment A75. is any one according to embodiment A1 to A74, wherein

L ¹Be key ,-D-alkylidene group-E-,-O-,-S-,-S (O)-,-S (O) ₂-,-C (O)-,-N (R ¹¹)-or-C (=N-OR ¹²), wherein

D, E, R ¹¹And R ¹²Be defined as implementing mode A1.

Embodiment A76. is according to the compound of embodiment A75, wherein

L ¹Be key ,-D-alkylidene group-E-,-O-,-C (O)-,-N (R ¹¹)-or-C (=N-OR ¹²)-, wherein

D, E, R ¹¹And R ¹²Be defined as implementing mode A1.

Embodiment A77. is according to the compound of embodiment A75, wherein

L ¹Be-O-.

Embodiment A78. is according to the compound of embodiment A75, wherein

L ¹Be-S-.

Embodiment A79. is according to the compound of embodiment A75, wherein

L ¹It is key.

Embodiment 80. is according to the compound of embodiment A75, wherein

L ¹Be-C (O)-.

The compound that embodiment A81. is any one according to embodiment A1 to A76, wherein

D be direct key or-O-;

E be direct key or-O-;

R ¹¹And R ¹²Be defined as implementing mode A1.

Embodiment A82. is according to the compound of embodiment A81, wherein

D is direct key.

Embodiment A83. is according to the compound of embodiment A81, wherein

D is-O-.

The compound that embodiment A84. is any one according to embodiment A81 to A83, wherein

E is direct key.

The compound that embodiment A85. is any one according to embodiment A81 to A83, wherein

E is-O-.

The compound that embodiment A86. is any one according to embodiment A1 to A85, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, it is bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-CON (H)-,-NHC (O)-,-NHCON (H)-,-NHSO ₂-,-SO ₂N (H)-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ¹⁶And R ¹⁷Be selected from hydrogen, aryl, heteroaryl, C _1-6-alkyl, C _1-6-alkoxyl group, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, C _1-6-alkoxyl group-arylidene-, C _1-6-alkoxyl group-inferior heteroaryl-, heteroaryl aryl-C _1-6-alkoxyl group-or aryl-C _1-6-alkoxyl group-;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A87. is according to the compound of embodiment A86, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, it is bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X be direct key ,-CH ₂-,-O-,-S-,-S (O ₂)-,-C (O)-,-CON (H)-,-NHC (O)-,-NHCON (H)-,-NHSO ₂-,-SO ₂N (H)-,-C (O)-O-,-O-C (O)-,-NHSO ₂NH-,

Wherein

R ¹⁶And R ¹⁷Be hydrogen;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A88. is according to the compound of embodiment A87, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

Perhaps

R ¹³And R ¹⁴Can constitute together and have formula-(CH ₂) _o-X-(CH ₂) _p-ring, it is bonded to R ¹³And R ¹⁴The nitrogen-atoms place that connects, wherein

O and p are 1,2,3 or 4 independently of one another;

X is direct key;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A89. is according to the compound of embodiment A88, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be independently from each other hydrogen, aryl, C _1-6-alkyl or aryl-C _1-6-alkylidene group-;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A90. is according to the compound of embodiment A89, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y and W ²Be independently of one another direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be hydrogen;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A91. is according to the compound of embodiment A90, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-S ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y is direct key;

W ²Be direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

R ¹³And R ¹⁴Be hydrogen;

R ¹³Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

Embodiment A92. is according to the compound of embodiment A90, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, N (R ¹³) (R ¹⁴)-C _1-6-alkylidene group-Y-and R ¹⁵-W ²-C _1-6-alkylidene group-Y-, wherein

Y be direct key ,-CH ₂-,-SO ₂-,-N (H) CO-,-N (H) SO ₂-or-O-C (O)-;

W ²It is direct key;

R ¹³And R ¹⁴Be hydrogen;

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C _1-6-alkyl or aryl-C _1-6The group of-alkylidene group-composition.

The compound that embodiment A93. is any one according to embodiment A90 to A92, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-S 2-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-, NH ₂-C _1-6-alkylidene group-and R ^15-C _1-6-alkylidene group-, wherein

R ¹⁵Be selected from by aryl, heteroaryl, cyclic hydrocarbon radical, heterocyclic radical, C ^1-6-alkyl or aryl-C ^1-6The group of-alkylidene group-composition.

Embodiment A94. is according to the compound of embodiment A93, wherein

R ¹¹Be selected from hydrogen, C _1-6-alkyl, aryl, carbamyl, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-NH-C (O)-, aryl-C _1-6-alkylidene group-NH-C (O)-, C _1-6-alkyl-SO ₂-, aryl-C _1-6-alkylidene group-SO ₂-, aryl-SO ₂-, SO ₂-, C _1-6-alkyl-C (O)-, aryl-C _1-6-alkylidene group-C (O)-and NH ₂-C _1-6-alkylidene group-.

Embodiment A95. is according to the compound of embodiment A94, wherein

R ¹¹Be hydrogen or C _1-6-alkyl.

Embodiment A96. is according to the compound of embodiment A95, wherein

R ¹¹Be hydrogen.

The compound that embodiment A97. is any one according to embodiment A1 to A96, wherein

R ¹²Be hydrogen or C _1-6-alkyl.

Embodiment A98. is according to the compound of embodiment A97, wherein

R ¹²Be hydrogen.

The compound that embodiment A99. is any one according to embodiment A1 to A98, wherein

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, cyclic hydrocarbon radical or heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹, C _3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as implementing mode A1.

Embodiment A100. is according to the compound of embodiment A99, wherein

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, cyclic hydrocarbon radical or heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as implementing mode A1.

Embodiment A101. is according to the compound of embodiment A99, wherein

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical or C _3-10-heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹, C _3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as implementing mode A1.

Embodiment A102. is according to the compound of embodiment A100 or embodiment A101, wherein

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical or C _3-10-heterocyclic radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed, wherein

R ¹⁸And R ¹⁹Be defined as implementing mode A1.

The compound that embodiment A103. is any one according to embodiment A99 to A102, wherein

G ¹Be selected from by methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl, the tertiary butyl, the 3-amyl group, the 2-amyl group, 3-methyl-butyl, the 2-propenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, the suberane base, oxetanyl, tetrahydrofuran base, THP trtrahydropyranyl, azetidinyl, pyrrolidyl, piperidyl, six hydrogen azepine _ bases, the thiacyclopentane base, tetrahydro thiapyran base, thia suberane base, 1,4-oxathiane base, 1,3-dioxolane base, 1,2-dithiolane base, 1,3-dithiolane base, six hydrogen-pyridazinyl, imidazolidyl, 1,3-two _ alkyl, morpholinyl, 1,3-dithiane base, 1,4-two _ alkyl, the group that 1,4-dithiane base or parathiazan base are formed.

Embodiment A104. is according to the compound of embodiment A103, wherein

G ¹Be selected from the group of being formed by methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl, the tertiary butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberane base, tetrahydrofuran base, THP trtrahydropyranyl, pyrrolidyl, piperidyl, six hydrogen azepine _ base, thiacyclopentane base, tetrahydro thiapyran base or thia suberane base.

Embodiment A105. is according to the compound of embodiment A104, wherein

G ¹Be selected from by methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, cyclopentyl, cyclohexyl, tetrahydrofuran base, THP trtrahydropyranyl, piperidyl or group that six hydrogen azepine _ base is formed.

Embodiment A106. is according to the compound of embodiment A105, wherein

G ¹Be selected from the group of being formed by isobutyl-, cyclopentyl and piperidyl.

Embodiment A107. is according to the compound of embodiment A105, wherein

G ¹It is isobutyl-.

Embodiment A108. is according to the compound of embodiment A105, wherein

G ¹It is cyclopentyl.

Embodiment A109. is according to the compound of embodiment A105, wherein

G ¹It is piperidyl.

The compound that embodiment A110. is any one according to embodiment A99 to A102, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment A111. is according to the compound of embodiment A110, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-aryl-C _1-6-alkylidene group-, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment A112. is according to the compound of embodiment A111, wherein

R ¹⁸And R ¹⁹Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A113. is according to the compound of embodiment A112, wherein

R ¹⁸Be hydrogen.

Embodiment A114. is according to the compound of embodiment A112 or A113, wherein

R ¹⁹Be hydrogen.

Embodiment A115. is according to the compound of embodiment A100 or embodiment A102, wherein

R ¹⁸And R ¹⁹When being connected in same nitrogen-atoms, constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

The compound that embodiment A116. is any one according to embodiment A1 to A98, wherein

G ¹Be alkyl or cyclic hydrocarbon radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed,

Perhaps G ¹Be aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein R ¹⁸, R ¹⁹, R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A117. is according to the compound of embodiment A116, wherein

G ¹Be C _1-6-alkyl or C _3-10-cyclic hydrocarbon radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6The group that-alkyl is formed,

Perhaps G ¹Be C _3-10-aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein R ¹⁸, R ¹⁹, R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A118. is according to the compound of embodiment A117, wherein

G ¹Be C _1-6-alkyl or C _3-10-cyclic hydrocarbon radical, it is replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR ¹⁸,-NR ¹⁸R ¹⁹And C _1-6-The group that alkyl is formed,

Perhaps G ¹Be phenyl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein R ¹⁸, R ¹⁹, R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A119. is according to the compound of embodiment A116, A117 or A118, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, heteroaryl-C _1-6-alkylidene group-, aryl-C _1-6-alkylidene group-, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, heteroaryl or aryl.

Embodiment A120. is according to the compound of embodiment A119, wherein

R ¹⁸And R ¹⁹Be hydrogen, C independently of one another _1-6-alkyl, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-aryl-C _1-6-alkylidene group-, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment A121. is according to the compound of embodiment A120, wherein

R ¹⁸And R ¹⁹Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A122. is according to the compound of embodiment A121, wherein

R ¹⁸Be hydrogen.

Embodiment A123. is according to the compound of embodiment A121 or A122, wherein

R ¹⁹Be hydrogen.

Embodiment A124. is according to the compound of embodiment A116 or embodiment A117, wherein

R ¹⁸And R ¹⁹When being connected in same nitrogen-atoms, constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

The compound that embodiment A125. is any one according to embodiment A116 to A124, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵With-C (O) OR ⁵⁴Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A126. is according to the compound of embodiment A125, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen ,-CN, C _1-6-alkyl ,-CF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-CH ₂C (O) OR ⁵⁴,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵With-C (O) OR ⁵⁴

Wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A127. is according to the compound of embodiment A126, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen or-OR ⁵⁴,

Wherein

R ⁵⁴Be hydrogen, C _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl.

Embodiment A128. is according to the compound of embodiment A126, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-aryl-C _1-6-alkylidene group-, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment A129. is according to the compound of embodiment A128, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A130. is according to the compound of embodiment A129, wherein

R ⁵⁴Be hydrogen.

Embodiment A131. is according to the compound of embodiment A129 or embodiment A130, wherein

R ⁵⁵Be hydrogen.

Embodiment A132. is according to the compound of embodiment A127, wherein

R ⁵⁴It is methyl.

The compound that embodiment A133. is any one according to embodiment A1 to A98, wherein

G ¹Be aryl or heteroaryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A134. is according to the compound of embodiment A133, wherein

G ¹Be C _3-10-aryl or C _3-10-heteroaryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A135. is according to the compound of embodiment A133, wherein

G ¹Be aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A136. is according to the compound of embodiment A135, wherein

G ¹Be C _3-10-aryl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

Embodiment A137. is according to the compound of embodiment A136, wherein

G ¹Be phenyl, it is alternatively by one or more substituent R ⁴⁰, R ⁴¹And R ⁴²Replace, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be defined as implementing mode A1.

The compound that embodiment A138. is any one according to embodiment A133 to A137, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen ,-CN ,-NO ₂, C _1-6-Alkyl ,-CHF ₂,-CF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵,-CH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵With-C (O) OR ⁵⁴Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A139. is according to the compound of embodiment A138, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen ,-CN, C _1-6-alkyl ,-CF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-NR ⁵⁴S (O) ₂R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-CH ₂C (O) OR ⁵⁴,-CH ₂OR ⁵⁴,-CH ₂NR ⁵⁴R ⁵⁵With-C (O) OR ⁵⁴

Wherein

R ⁵⁴And R ⁵⁵Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A140. is according to the compound of the compound of embodiment A139, wherein

R ⁴⁰, R ⁴¹And R ⁴²Be independently of one another

Halogen or-OR ⁵⁴,

Wherein

R ⁵⁴Be hydrogen, C _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl.

The compound that embodiment A141. is any one according to embodiment A138 to A139, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-aryl-C _1-6-alkylidene group-, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment A142. is according to the compound of embodiment A141, wherein

R ⁵⁴And R ⁵⁵Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A143. is according to the compound of embodiment A142, wherein

R ⁵⁴Be hydrogen.

Embodiment A144. is according to the compound of embodiment A142 or embodiment A143, wherein

R ⁵⁵Be hydrogen.

Embodiment A145. is according to the compound of embodiment A140, wherein

R ⁵⁴It is methyl.

Embodiment A146. is according to the compound of embodiment A135, wherein

G ¹Be

Wherein

R ⁵⁶, R ⁵⁷, R ⁵⁸, R ⁵⁹With ⁶⁰Be independently of one another hydrogen or halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²,-SR ⁶¹,-NR ⁶¹S (O) ₂R ⁶²,-S (O) ₂NR ⁶¹R ⁶²,-S (O) NR ⁶¹R ⁶²,-S (O) R ⁶¹,-S (O) ₂R ⁶¹,-C (O) NR ⁶¹R ⁶²,-OC (O) NR ⁶¹R ⁶²,-NR ⁶¹C (O) R ⁶²,-CH ₂C (O) NR ⁶¹R ⁶²,-CH ₂C (O) OR ⁶¹,-OCH ₂C (O) NR ⁶¹R ⁶²,-CH ₂OR ⁶¹,-CH ₂NR ⁶¹R ⁶²,-OC (O) R ⁶¹,-C (O) R ⁶¹With-C (O) OR ⁶¹Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃-OCF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²And C _1-6-alkyl;

C _3-10-cyclic hydrocarbon radical, C _4-8-cycloalkenyl group, heterocyclic radical, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, C _3-10-cyclic hydrocarbon radical-C _1-6-alkylthio-, C _3-10-cyclic hydrocarbon sulfenyl, C _3-10-cyclic hydrocarbon radical-C _2-6-alkenylene-, C _3-10-cyclic hydrocarbon radical-C _2-6-alkynylene-, C _4-8-cycloalkenyl group-C _1-6-alkylidene group-, C _4-8-cycloalkenyl group-C _2-6-alkenylene-, C _4-8-cycloalkenyl group-C _2-6-alkynylene-, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical-C _2-6-alkenylene-, heterocyclic radical-C _2-6-alkynylene-; Perhaps

Aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, aryl-C _2-6-alkenylene-, aryl-C _2-6-alkynylene-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, heteroaryl-C _2-6-alkenylene-and heteroaryl-C _2-6-alkynylene-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁶¹,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁶¹,-NR ⁶¹R ⁶²Or C _1-6-alkyl, wherein

R ⁶¹And R ⁶²Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁶¹And R ⁶²When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A147. is according to the compound of embodiment A146, wherein

R ⁵⁶, R ⁵⁷, R ⁵⁸, R ^{59 Hes}R ⁶⁰Be independently of one another

Halogen ,-CN ,-NO ₂, C _1-6-alkyl ,-CHF _2,-CF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²,-SR ⁶¹,-NR ⁶¹S (O) ₂R ⁶²,-S (O) ₂NR ⁶¹R ⁶²,-S (O) NR ⁶¹R ⁶²,-S (O) R ⁶¹,-S (O) ₂R ⁶¹,-C (O) NR ⁶¹R ⁶²,-OC (O) NR ⁶¹R ⁶²,-NR ⁶¹C (O) R ⁶²,-CH ₂C (O) NR ⁶¹R ⁶²,-CH ₂C (O) OR ⁶¹,-OCH ₂C (O) NR ⁶¹R ⁶²,-CH ₂OR ⁷,-CH ₂NR ⁶¹R ⁶²With-C (O) OR ⁶¹Perhaps

C _2-6-thiazolinyl and C _2-6-alkynyl, they can be replaced by one or more substituting groups alternatively, and described substituting group is selected from-CN ,-CF ₃,-OCF ₃,-OR ⁶¹,-NR ⁶¹R ⁶²And C _1-6-alkyl, wherein

R ⁶¹And R ⁶²Be hydrogen, C independently of one another _1-6-alkyl, C _1-6-alkyl-arylidene-, C _1-6-alkyl-inferior heteroaryl-, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heteroaryl or aryl;

Perhaps

R ⁶¹And R ⁶²When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A148. is according to the compound of embodiment A146 or embodiment A147, wherein

R ⁵⁶Or R ⁵⁷Be-OR ⁶¹

Embodiment A149. is according to the compound of embodiment A148, wherein

R ⁶¹It is methyl.

Embodiment A150. is according to the compound of embodiment A147, wherein

R ⁶¹And R ⁶²Be hydrogen or C independently of one another _1-6-alkyl, C _1-6-alkyl-C _3-10-arylidene-, C _1-6-alkyl-C _3-10-inferior heteroaryl-, C _3-10-aryl-C _1-6-alkylidene group-, C _3-10-heteroaryl-C _1-6-alkylidene group-, C _3-10-heteroaryl or C _3-10-aryl.

Embodiment A151. is according to the compound of embodiment A150, wherein

R ⁶¹And R ⁶²Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A152. is according to the compound of embodiment A151, wherein

R ⁶¹Be hydrogen.

Embodiment A153. is according to the compound of embodiment A151 or embodiment A152, wherein

R ⁶²Be hydrogen.

The compound that embodiment A154. is any one according to embodiment A146 to A153, wherein

R ⁵⁶, R ⁵⁷, R ⁵⁸, R ⁵⁹And R ⁶⁰In have at least one to be hydrogen.

Embodiment A155. is according to the compound of embodiment A154, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least two to be hydrogen.

Embodiment A156. is according to the compound of embodiment A155, wherein

R ²³, R ²⁴, R ²⁵And R ²⁶In have at least three to be hydrogen.

The compound that embodiment A157. is any one according to embodiment A1 to A156, wherein

L ²Be direct key, C _1-6-alkylidene group, C _2-6-alkenylene, C _2-6-alkynylene ,-N-R ²⁰-,-C _1-6-alkylidene group-N (R ²⁰)-,-C _2-6-alkenylene-N (R ²⁰)-or-C _2-6-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be defined as implementing mode A1.

The compound that embodiment A158. is any one according to embodiment A1 to A153, wherein

L ²Be-N-R ²⁰-,-alkylidene group-N (R ²⁰)-,-alkenylene-N (R ²⁰)-or-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be defined as implementing mode A1.

Embodiment A159. is according to the compound of embodiment A157 or embodiment A158, wherein

L ²Be-N-R ²⁰-,-C _1-6-alkylidene group-N (R ²⁰)-,-C _2-6-alkenylene-N (R ²⁰)-or-C _2-6-alkynylene-N (R ²⁰)-, wherein

R ²⁰Be defined as implementing mode A1.

Embodiment A160. is according to the compound of embodiment A159, wherein

L ²Be-N-R ²⁰-, wherein

R ²⁰Be defined as implementing mode A1.

Embodiment A161. is according to the compound of embodiment A157, wherein

L ²It is direct key.

The compound that embodiment A162. is any one according to embodiment A1 to A160, wherein

R ²⁰Be hydrogen, perhaps

R ²⁰Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical-W ³, C _3-10-heterocyclic radical-W ³, C _3-10-aryl-W ³-or C _4-10-heteroaryl-W ³-, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

W ³, R ³⁰, R ³¹And R ³²Be defined as implementing mode A1.

Embodiment A163. is according to the compound of embodiment A162, wherein

W ³It is alkylidene group.

Embodiment A164. is according to the compound of embodiment A163, wherein

W ³Be C _2-6-alkylidene group.

Embodiment A165. is according to the compound of embodiment A162, wherein

W ³It is direct key.

The compound that embodiment A166. is any one according to embodiment A1 to A160, wherein

R ²⁰Be hydrogen, C _1-6-alkyl, C _2-6-thiazolinyl or C _2-6-alkynyl, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

R ³⁰, R ³¹And R ³²Be defined as implementing mode A1.

The compound that embodiment A167. is any one according to embodiment A162 to A166, wherein

R ²⁰Be hydrogen, perhaps

R ²⁰Be C _1-6-alkyl, C _1-6-thiazolinyl or C _1-6-alkynyl, it is alternatively by one or more substituent R ³⁰, R ³¹And R ³²Replace, wherein

R ³⁰, R ³¹And R ³²Be defined as implementing mode A1.

The compound that embodiment A168. is any one according to embodiment A1 to A167, wherein

R ³⁰, R ³¹And R ³²Be independently from each other-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵²,-NR ⁵²R ⁵³,-SR ⁵²,-NR ⁵²S (O) ₂R ⁵³,-S (O) ₂NR ⁵²R ⁵³,-S (O) NR ⁵²R ⁵³,-S (O) R ⁵²,-S (O) ₂R ⁵²,-C (O) NR ⁵²R ⁵³,-OC (O) NR ⁵²R ⁵³,-NR ⁵²C (O) R ⁵³,-CH ₂C (O) NR ⁵²R ⁵³,-OCH ₂C (O) NR ⁵²R ⁵³,-CH ₂OR ⁵²,-CH ₂NR ⁵²R ⁵³,-OC (O) R ⁵²,-C (O) R ⁵²With-C (O) OR ⁵², wherein

R ⁵²And R ⁵³Be defined as implementing mode A1.

Embodiment A169. is according to the compound of embodiment A168, wherein

R ⁵²And R ⁵³When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

The compound that embodiment A170. is any one according to embodiment A1 to A168, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-heteroaryl-C _1-6-alkylidene group-heteroaryl or aryl.

Embodiment A171. is according to the compound of embodiment A170, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment A172. is according to the compound of embodiment A171, wherein

R ⁵²And R ⁵³Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A173. is according to the compound of embodiment A172, wherein

R ⁵²Be hydrogen.

Embodiment A174. is according to the compound of embodiment A172 or embodiment A173, wherein

R ⁵³Be hydrogen.

Embodiment A175. is according to the compound of embodiment A167, wherein

R ²⁰Be hydrogen.

The compound that embodiment A176. is any one according to embodiment A1 to A175, wherein

L ³Be-C (O)-,-C (O)-C (O)-or-C (O) CH ₂C (O)-.

Embodiment A177. is according to the compound of embodiment A176, wherein

L ³Be-C (O)-.

Embodiment A178. is according to the compound of embodiment A176, wherein

L ³Be-C (O)-C (O)-.

Embodiment A179. is according to the compound of embodiment A176, wherein

L ³Be-C (O) CH ₂C (O)-.

The compound that embodiment A180. is any one according to embodiment A1 to A179, wherein

R ¹Be hydrogen, perhaps

R ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical-W ⁴, C _3-10-heterocyclic radical-W ⁴, C _3-10-aryl-W ⁴-or C _4-10-heteroaryl-W ⁴, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

W ⁴, R ³³, R ³⁴And R ³⁵Be defined as implementing mode A1.

Embodiment A181. is according to the compound of embodiment A180, wherein

W ⁴It is alkylidene group.

Embodiment A182. is according to the compound of embodiment A181, wherein

W ⁴Be C _2-6-alkylidene group.

Embodiment A183. is according to the compound of embodiment A180, wherein

W ⁴It is direct key.

The compound that embodiment A184. is any one according to embodiment A1 to A176, wherein

R ¹Be hydrogen, C _1-6-alkyl, C _2-6-thiazolinyl or C _2-6-alkynyl, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

R ³³, R ³⁴And R ³⁵Be defined as implementing mode A1.

The compound that embodiment A185. is any one according to embodiment A180 to A184, wherein

R ¹Be hydrogen, C _1-6-alkyl, C _2-6-thiazolinyl or C _2-6-alkynyl, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

R ³³, R ³⁴And R ³⁵Be defined as implementing mode A1.

Embodiment A186. is according to the compound of embodiment A185, wherein

R ¹Be hydrogen or C _1-6-alkyl, it is alternatively by one or more substituent R ³³, R ³⁴And R ³⁵Replace, wherein

R ³³, R ³⁴And R ³⁵Be defined as implementing mode A1.

The compound that embodiment A187. is any one according to embodiment A1 to A186, wherein

R ³³, R ³⁴And R ³⁵Be independently from each other-CHF ₂,-CF ₃,-OCF ₃,-OCHF ₂,-OCH ₂CF ₃,-OCF ₂CHF ₂,-S (O) ₂CF ₃,-SCF ₃,-OR ⁵²,-NR ⁵²R ⁵³,-SR ⁵²,-NR ⁵²S (O) ₂R ⁵³,-S (O) ₂NR ⁵²R ⁵³,-S (O) NR ⁵²R ⁵³,-S (O) R ⁵²,-S (O) ₂R ⁵²,-C (O) NR ⁵²R ⁵³,-OC (O) NR ⁵²R ⁵³,-NR ⁵²C (O) R ⁵³,-CH ₂C (O) NR ⁵²R ⁵³,-OCH ₂C (O) NR ⁵²R ⁵³,-CH ₂OR ⁵²,-CH ₂NR ⁵²R ⁵³,-OC (O) R ⁵²,-C (O) R ⁵²With-C (O) OR ⁵², wherein

R ⁵²And R ⁵³Be defined as implementing mode A1.

Embodiment A188. is according to the compound of embodiment A186, wherein

R ⁵²And R ⁵³When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively.

Embodiment A189. is according to the compound of embodiment A186, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-heteroaryl-C _1-6-alkylidene group-heteroaryl or aryl.

Embodiment A190. is according to the compound of embodiment A189, wherein

R ⁵²And R ⁵³Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-or aryl.

Embodiment A191. is according to the compound of embodiment A190, wherein

R ⁵²And R ⁵³Be hydrogen or C independently of one another _1-6-alkyl.

Embodiment A192. is according to the compound of embodiment A191, wherein

R ⁵²Be hydrogen.

Embodiment A193. is according to the compound of embodiment A191 or embodiment A192, wherein

R ⁵³Be hydrogen.

Embodiment A194. is according to the compound of embodiment A186, wherein

R ¹Be hydrogen.

The compound that embodiment A195. is any one according to embodiment A1 to A194, wherein

G ²Be heteroaryl, annelated heterocycles base heteroaryl or fused rings alkyl heteroaryl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possesses and is connected G ²With-N (R ¹)-the adjacent nitrogen-atoms of atom, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as implementing mode A1.

Embodiment A196. is according to the compound of embodiment A195, wherein

G ²Be fused rings alkyl heteroaryl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possesses and is connected G ²With-N (R ¹)-the adjacent nitrogen-atoms of atom, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as implementing mode A1.

Embodiment A197. is according to the compound of embodiment A196, wherein

G ²Be fused rings alkyl thiazolyl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as implementing mode A1.

Embodiment A198. is according to the compound of embodiment A197, wherein

G ²Be fused rings alkyl thiazolyl, it is replaced by-COOH alternatively.

Embodiment A199. is according to the compound of embodiment A195, wherein

G ²Be heteroaryl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein said heteroaryl possesses and is connected G ²With-N (R ¹)-the adjacent nitrogen-atoms of atom, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as implementing mode A1.

Embodiment A200. is according to the compound of embodiment A199, wherein

G ²Be furyl, thienyl, thiophenyl, pyrryl, imidazolyl, pyrazolyl, triazolyl, tetrazyl, thiazolyl, _ the azoles base, different _ the azoles base, _ di azoly, thiadiazolyl group, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl, indyl or indazolyl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as implementing mode A1.

Embodiment A201. is according to the compound of embodiment A200, wherein

G ²Be thiazolyl, it is alternatively by one or more substituent R ⁴³, R ⁴⁴And R ⁴⁵Replace, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be defined as implementing mode A1.

Embodiment A202. is according to the compound of embodiment A201, wherein G ²Be

Wherein

R ⁴³And R ⁴⁴Be defined as implementing mode A1.

Embodiment A203. is according to the compound of embodiment A202, wherein G ²Be

Wherein

R ⁴³Be defined as implementing mode A1.

Embodiment A204. is according to the compound of embodiment A202, wherein G ²Be

Wherein

R ⁴³And R ⁴⁴Be defined as implementing mode A1.

Embodiment A205. is according to the compound of embodiment A200, wherein G ²Be

Wherein

R ⁴³Be defined as implementing mode A1.

Embodiment A206. is according to the compound of embodiment A202, wherein G ²Be

Wherein

R ⁴⁴Be defined as implementing mode A1.

The compound that embodiment A207. is any one according to embodiment A1 to A206, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other

-CN ,-NO ₂,-SCF ₃,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-S (O) ₂NR ⁵⁴R ⁵⁵,-S (O) NR ⁵⁴R ⁵⁵,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵,-OC (O) NR ⁵⁴R ⁵⁵,-NR ⁵⁴C (O) R ⁵⁵, halogen ,-S-C _1-6-alkylidene group-OR ⁵⁴,-S (O) ₂-C _1-6-alkylidene group-OR ⁵⁴,-C _1-6-alkylidene group-S-R ⁵⁴,-C _1-6-alkylidene group-S (O) R ⁵⁴,-C _1-6-alkylidene group-S (O) ₂R ⁵⁴,-C _1-6-alkylidene group-N (R ⁵⁴) S (O) ₂R ⁵⁵,-N (R ⁵⁴) S (O) ₂R ⁵⁵,-C _1-6-alkylidene group-C (O) NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) R ⁵⁵,-N (R ⁵⁴) C (O) R ⁵⁵,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) NR ⁵⁵R ⁵⁶, C _1-6-alkylidene group-NHC (=NR ⁵⁴) NR ⁵⁵R ⁵⁶,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) OR ⁵⁵,-N (R ⁵⁴) C (O) OR ⁵⁵,-C _1-6-alkylidene group-C (O) OR ⁵⁴,-OCH ₂C (O) NR ⁵⁴R ⁵⁵,-O (CH ₂) _1-3OR ⁵⁴,-C _1-6-alkylidene group-O-R ⁵⁴,-C _1-6-alkylidene group-C (O) R ⁵⁴,-C _1-6-alkylidene group-NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group=N-O-R ⁵⁴,-C ^1-6-alkylidene group-N (R ⁵⁴) S (O) ₂NR ⁵⁵R ⁵⁶,-N (R ⁵⁴) S (O) ₂NR ⁵⁵R ⁵⁶,-N (R ⁵⁴) S (O) ₂NR ⁵⁵R ⁵⁶,-OC (O) R ⁵⁴,-C (O) N (R ⁵⁴) S (O) ₂R ⁵⁵,-C _1-6-alkylidene group-C (R ⁵⁴)=N-OR ⁵⁵,-NHC (=NR ⁵⁴) NR ⁵⁵R ⁵⁶,-C _1-6-alkylidene group-N=C (N (R ⁵⁴R ⁵⁵)) ₂,-N=C (N (R ⁵⁴R ⁵⁵)) ₂,-C (O) R ⁵⁴With-C (O) OR ⁵⁴Perhaps

C _1-6-alkyl or C _2-6-thiazolinyl, they can be replaced by one or more substituting groups separately alternatively, and described substituting group is independently selected from halogen, R ⁵⁴,-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-C (O) OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl; Perhaps

C _3-10-cyclic hydrocarbon radical, heterocyclic radical, C _3-11-cyclic hydrocarbon radical-C _1-6-alkylidene group-, C _3-10-cyclic hydrocarbon radical-C _1-6-alkoxyl group-, C _3-10-ring-oxyl, heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical part wherein alternatively can be by one or more R that independently are selected from ⁷⁰Substituting group replace; Perhaps

Aryl, aryloxy, aryl-C _1-6-alkoxyl group-, aryl-C _1-6-alkylidene group-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be defined as implementing mode A1.

Embodiment A208. is according to the compound of embodiment A207, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other

-OR ⁵⁴,-NR ⁵⁴R ⁵⁵,-SR ⁵⁴,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴,-C (O) NR ⁵⁴R ⁵⁵, halogen ,-S-C _1-6-alkylidene group-OR ⁵⁴,-C _1-6-alkylidene group-S-R ⁵⁴,-C _1-6-alkylidene group-S (O) R ⁵⁴,-C _1-6-alkylidene group-S (O) ₂R ⁵⁴,-C _1-6-alkylidene group-N (R ⁵⁴) S (O) ₂R ⁵⁵,-C _1-6-alkylidene group-C (O) NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) R ⁵⁵,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) NR ⁵⁵R ⁵⁶, C _1-6-alkylidene group-NHC (=NR ⁵⁴) NR ⁵⁵R ⁵⁶,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) OR ⁵⁵,-C _1-6-alkylidene group-C (O) OR ⁵⁴,-C _1-6-alkylidene group-O-R ⁵⁴,-C _1-6-alkylidene group-C (O) R ⁵⁴,-C _1-6-alkylidene group-NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group=N-O-R ⁵⁴,-C _1-6-alkylidene group-N=C (N (R ⁵⁴R ⁵⁵)) ₂,-N=C (N (R ⁵⁴R ⁵⁵)) ₂,-C (O) R ⁵⁴With-C (O) OR ⁵⁴Perhaps

C _1-6-alkyl, it is replaced by one or more substituting groups alternatively, and described substituting group is independently selected from halogen, R ⁵⁴,-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-C (O) OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl; Perhaps

Heterocyclic radical or heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical part wherein alternatively can be by one or more R that independently are selected from ⁷⁰Substituting group replace; Perhaps

Aryl, aryl-C _1-6-alkylidene group-, heteroaryl, heteroaryl-C _1-6-alkylidene group-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴, R ⁵⁵, R ⁵⁶And R ⁷⁰Be defined as implementing mode A1.

Embodiment A209. is according to the compound of embodiment A208, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other

-SR ⁵⁴,-S (O) R ⁵⁴,-S (O) ₂R ⁵⁴, halogen ,-C _1-6-alkylidene group-S-R ⁵⁴,-C _1-6-alkylidene group-S (O) R ⁵⁴,-C _1-6-alkylidene group-S (O) ₂R ⁵⁴,-C _1-6-alkylidene group-N (R ⁵⁴) C (O) OR ⁵⁵,-C _1-6-alkylidene group-C (O) OR ⁵⁴,-C _1-6-alkylidene group-O-R ⁵⁴,-C _1-6-alkylidene group-NR ⁵⁴R ⁵⁵,-C _1-6-alkylidene group-C (O) R ⁵⁴,-C (O) R ⁵⁴With-C (O) OR ⁵⁴Perhaps

C _1-6-alkyl, it is replaced by one or more substituting groups alternatively, and described substituting group is independently selected from halogen, R ⁵⁴,-CN ,-CF ₃,-OCF ₃,-OR ⁵⁴,-C (O) OR ⁵⁴,-NR ⁵⁴R ⁵⁵And C _1-6-alkyl; Perhaps

Heterocyclic radical or heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical part wherein alternatively can be by one or more R that independently are selected from ⁷⁰Substituting group replace; Perhaps

Heteroaryl or heteroaryl-C _1-6-Ya-alkyl-, aryl wherein and heteroaryl moieties can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴, R ⁵⁵, R ⁵⁶And R ⁷⁰Be defined as implementing mode A1.

Embodiment A210. is according to the compound of embodiment A209, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other

-SR ⁵⁴,-S (O) ₂R ⁵⁴, halogen ,-C _1-6-alkylidene group-C (O) OR ⁵⁴With-C (O) OR ⁵⁴Perhaps

Heterocyclic radical or heterocyclic radical-C _1-6-alkylidene group-, heterocyclic radical part wherein alternatively can be by one or more R that independently are selected from ⁷⁰Substituting group replace; Perhaps

Heteroaryl or heteroaryl-C _1-6-alkylidene group-, heteroaryl moieties wherein can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴, R ⁵⁵, R ⁵⁶And R ⁷⁰Be defined as implementing mode A1.

Embodiment A211. is according to the compound of embodiment A210, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other

-SR ⁵⁴,-S (O) ₂R ⁵⁴, halogen ,-C _1-6-alkylidene group-C (O) OR ⁵⁴With-C (O) OR ⁵⁴Perhaps

Heterocyclic radical-C _1-6-alkylidene group-, wherein heterocyclic radical is selected from imidazolyl, piperidyl, piperazinyl and morpholinyl,

Heterocyclic radical part wherein alternatively can be by one or more R that independently are selected from ⁷⁰Substituting group replace; Perhaps

Heteroaryl or heteroaryl-C _1-6-alkylidene group-, wherein heteroaryl is selected from thiazolyl, triazolyl or tetrazyl,

Heteroaryl moieties wherein can be replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴, R ⁵⁵, R ⁵⁶And R ⁷⁰Be defined as implementing mode A1.

Embodiment A212. is according to the compound of embodiment A209, wherein

R ⁴³, R ⁴⁴And R ⁴⁵Be independently from each other-C _1-6-alkylidene group-S-R ⁵⁴,-C _1-6-alkylidene group-O-R ⁵⁴,-C _1-6-alkylidene group-S (O) ₂R ⁵⁴Or-C _1-6-alkylidene group-NR ⁵⁴R ⁵⁵, wherein

R ⁵⁴And R ⁵⁵Be defined as implementing mode A1.

Embodiment A213. is according to the compound of embodiment A209, wherein

R ⁴³Be-C _1-6-alkylidene group-S-R ⁵⁴, wherein

R ⁵⁴Be defined as implementing mode A1.

Embodiment A214. wherein

R ⁴³Be-C _1-6-alkylidene group-O-R ⁵⁴, wherein

R ⁵⁴Be defined as implementing mode A1.

Embodiment A215. wherein

R ⁴³Be-C _1-6-alkylidene group-NR ⁵⁴R ⁵⁵, wherein

R ⁵⁴With ⁵⁵Be defined as implementing mode A1.

Embodiment A216. wherein

R ⁴³Be-C _1-6-alkylidene group-S (O) ₂R ⁵⁴, wherein

R ⁵⁴Be defined as implementing mode A1.

The compound that embodiment A217. is any one according to embodiment 207 to 210, wherein

R ⁴³Be heteroaryl or heteroaryl-C _1-6-alkylidene group-, it is replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be defined as implementing mode A1.

Embodiment A218. is according to the compound of embodiment A217, wherein

R ⁴³Be heteroaryl, it is replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be defined as implementing mode A1.

Embodiment A219. is according to the compound of embodiment A217, wherein

R ⁴³Be heteroaryl-C _1-6-alkylidene group-, it is replaced by one or more substituting groups alternatively, described substituting group be selected from halogen ,-C (O) OR ⁵⁴,-CN ,-CF ₃,-OCF ₃,-NO ₂,-OR ⁵⁴,-NR ⁵⁴R ⁵⁵Or C _1-6-alkyl, wherein

R ⁵⁴And R ⁵⁵Be defined as implementing mode A1.

The compound that embodiment A220. is any one according to embodiment A207 to A211, wherein R ⁷⁰Be=O, methyl or C (O) OR ⁷⁵

The compound that embodiment A221. is any one according to embodiment A207 to A211, wherein R ⁷⁰Be-C (O) OH.

The compound that embodiment A222. is any one according to embodiment A207 to A211, wherein R ⁷⁰Be-(CH ₂) _1-3C (O) OH.

The compound that embodiment A223. is any one according to embodiment A207 to A211, wherein R ⁷⁰Be-S (O) ₂CH ₃

Embodiment A224. is according to the compound of embodiment A211, wherein R ⁴³Be-C _1-6-alkylidene group-C (O) OR ⁵⁴

Embodiment A225. is according to the compound of embodiment A224, wherein R ⁴³Be-CH ₂-C (O) OR ⁵⁴

Embodiment A226. is according to the compound of embodiment A211, wherein R ⁴⁴Be-SR ⁵⁴

Embodiment A227. is according to the compound of embodiment A211, wherein R ⁴⁴Be-S (O) ₂R ⁵⁴

Embodiment A228. is according to the compound of embodiment A211, wherein R ⁴⁴It is halogen.

The compound that embodiment A229. is any one according to embodiment A1 to A228, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, C independently of one another _1-6-alkyl, aryl-C _1-6-alkylidene group-, heteroaryl-C _1-6-alkylidene group-, heterocyclic radical, heterocyclic radical-C _1-6-alkylidene group-, heteroaryl or aryl, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace;

Perhaps

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁷²) _u-(CHR ⁷³) _v-W ⁶,

Perhaps

R ⁵⁴And R ⁵⁵When being connected in same nitrogen-atoms, can constitute 3 to 8 yuan of heterocycles with described nitrogen-atoms, wherein contain the extra heteroatoms that one or two is selected from nitrogen, oxygen and sulphur alternatively, and contain one or two two keys alternatively, and alternatively by one or more C _1-6-alkyl replaces,

R wherein ⁷¹, R ⁷², R ⁷³, u, v and W ⁶Be defined as implementing mode A1.

Embodiment A230. is according to the compound of embodiment A229, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, C independently of one another _1-6-alkyl, heterocyclic radical, heterocyclic radical-C _1-6-alkylidene group-, heteroaryl or aryl, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace;

Perhaps

R ⁵⁴And R ⁵⁵Be independently of one another hydrogen or-(CHR ⁷²) _u-(CHR ⁷³) _v-W ⁶,

R wherein ⁷¹, R ⁷², R ⁷³, u, v and W ⁶Be defined as implementing mode A1.

The compound that embodiment A231. is any one according to embodiment A1 to A230, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl, the tertiary butyl, 3-amyl group, 2-amyl group or 3-methyl-butyl independently of one another.

Embodiment A232. is according to the compound of embodiment A231, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl or the tertiary butyl independently of one another.

Embodiment A233. is according to the compound of embodiment A232, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl or the tertiary butyl independently of one another.

Embodiment A234. is according to the compound of embodiment A233, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be hydrogen, methyl or ethyl independently of one another.

Embodiment A235. is according to the compound of embodiment A234, wherein

R ⁵⁴Be hydrogen.

The compound that embodiment A236. is any one according to embodiment A1 to A230, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be oxetanyl independently of one another, tetrahydrofuran base, THP trtrahydropyranyl, oxepane alkyl (oxepanyl), azetidinyl, pyrrolidyl, piperidyl, six hydrogen azepine _ bases, Thietane base (thietanyl), thiacyclopentane base (thiolanyl), tetrahydro thiapyran base, thia suberane base (thiepanyl), 1,4-oxathiane base, 1,3-dioxolane base, 1,2-dithiolane base, 1,3-dithiolane base, six hydrogen-pyridazinyl, imidazolidyl, 1,3-two _ alkyl, morpholinyl, 1,3-dithiane base, 1,4-two _ alkyl, 1,4-dithiane base or parathiazan base, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A237. is according to the compound of embodiment A236, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be THP trtrahydropyranyl, oxepane alkyl, piperidyl, six hydrogen azepine _ base, tetrahydro thiapyran base, thia suberane base, 1 independently of one another, 4-oxathiane base, 1,3-dithiolane base, six hydrogen-pyridazinyl, 1,3-two _ alkyl, morpholinyl, 1,3-dithiane base, 1,4-two _ alkyl, 1,4-dithiane base or thio-morpholinyl, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A238. is according to the compound of embodiment A237, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be THP trtrahydropyranyl, piperidyl, tetrahydro thiapyran base, 1 independently of one another, 4-oxathiane base, six hydrogen-pyridazinyl, morpholinyl, 1,4-two _ alkyl, 1,4-dithiane base or thio-morpholinyl, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A239. is according to the compound of embodiment A238, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be THP trtrahydropyranyl, piperidyl, tetrahydro thiapyran base or morpholinyl independently of one another, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A240. is according to the compound of embodiment A239, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be piperidyl or morpholinyl independently of one another, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A241. is according to the compound of embodiment A240, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be piperidyl or morpholinyl independently of one another.

242。

The compound that embodiment A243. is any one according to embodiment A1 to A230,

Wherein

R ⁵⁴, R ⁵⁵With ⁵⁶Be independently of one another furyl, thienyl, thiophenyl, pyrryl, imidazolyl, pyrazolyl, triazolyl, tetrazyl, thiazolyl, _ the azoles base, different _ the azoles base, _ di azoly, thiadiazolyl group, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, benzofuryl, benzothienyl, indyl, purine radicals or indazolyl, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A244. is according to the compound of embodiment A243, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be independently of one another furyl, thienyl, thiophenyl, pyrryl, imidazolyl, pyrazolyl, triazolyl, tetrazyl, thiazolyl, _ the azoles base, different _ the azoles base, _ di azoly, thiadiazolyl group, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidyl, benzofuryl, indyl or purine radicals, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A245. is according to the compound of embodiment A244, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be imidazolyl, triazolyl, tetrazyl, thiazolyl, pyridyl, pyrimidyl, benzofuryl, indyl or purine radicals independently of one another, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A246. is according to the compound of embodiment A245, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be imidazolyl, triazolyl, tetrazyl, thiazolyl, pyridyl, pyrimidyl or purine radicals independently of one another, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A247. is according to the compound of embodiment A246, wherein

R ⁵⁴, R ⁵⁵And R ⁵⁶Be imidazolyl, triazolyl, tetrazyl, thiazolyl, pyridyl, pyrimidyl independently of one another, they are separately alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A248. is according to the compound of embodiment A247, wherein

R ⁵⁴Be imidazolyl, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A249. is according to the compound of embodiment A247, wherein

R ⁵⁴Be triazolyl, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A250. is according to the compound of embodiment A247, wherein

R ⁵⁴Be tetrazyl, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A251. is according to the compound of embodiment A247, wherein

R ⁵⁴Be thiazolyl, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A252. is according to the compound of embodiment A247, wherein

R ²⁴Be pyridyl, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A253. is according to the compound of embodiment A247, wherein

R ⁵⁴Be pyrimidyl, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

Embodiment A254. is according to the compound of embodiment A246, wherein

R ⁵⁴Be purine radicals, it is alternatively by one or more R that independently are selected from ⁷¹Substituting group replace R wherein ⁷¹Be defined as implementing mode A1.

The compound that embodiment A255. is any one according to embodiment A1 to A254, wherein

R ⁷¹Be methyl or=O.

The compound that embodiment A256. is any one according to embodiment A1 to A254, wherein

R ⁷¹Be-C (O) OH.

The compound that embodiment A257. is any one according to embodiment A1 to A254, wherein

R ⁷¹Be-(CH ₂) _1-3C (O) OH.

The compound that embodiment A258. is any one according to embodiment A1 to A254, wherein

R ⁷⁰Be-(CH ₂) _1-3NR ⁷⁵R ⁷⁶

The compound that embodiment A259. is any one according to embodiment A1 to A230, wherein

U is 0 or 1.

Embodiment A260. is according to the compound of embodiment A259, wherein

U is 0.

Embodiment A261. is according to the compound of embodiment A259, wherein

U is 1.

The compound that embodiment A262. is any one according to embodiment A1 to A230, wherein

V is 0 or 1.

Embodiment A263. is according to the compound of embodiment A262, wherein

V is 0.

Embodiment A264. is according to the compound of embodiment A262, wherein

V is 1.

The compound that embodiment A265. is any one according to embodiment A1 to A230, wherein

U is that 0, v is 1.

The compound that embodiment A266. is any one according to embodiment A1 to A230, wherein

U and v are 0.

Embodiment A267. is according to embodiment A1 to A230 or any one compound of A259 to A266, wherein

R ⁷²And R ⁷³Be independently selected from hydrogen, hydroxyl or-C (O) OR ⁷⁵

Embodiment A268. is according to the compound of embodiment A267, wherein

R ⁷²And R ⁷³Be independently selected from hydrogen or-C (O) OR ⁷⁵, R wherein ⁷⁵Be defined as implementing mode A1.

Embodiment A269. is according to the compound of embodiment A267, wherein

R ⁷²And R ⁷³Be hydrogen.

Embodiment A270. is according to embodiment A1 to A230 or any one compound of A259 to A269, wherein

W ⁶Be-O-R ⁷⁵,-C (O) O-R ⁷⁵,-C (O)-R ⁷⁵,-NR ⁷⁵R ⁷⁶,-NHCH ₂C (O) R ⁷⁵,-NHC (O) R ⁷⁵,-S (O) ₂R ⁷⁵,-NHS (O) ₂R ⁷⁵, perhaps

W ⁶Be heterocyclic radical, R wherein ⁷⁵And R ⁷⁶Be defined as implementing mode A1.

Embodiment A271. is according to the compound of embodiment A270, wherein

W ⁶Be-O-R ⁷⁵,-C (O) O-R ⁷⁵,-C (O)-R ⁷⁵,-NR ⁷⁵R ⁷⁶,-NHCH ₂C (O) R ⁷⁵,-NHC (O) R ⁷⁵,-S (O) ₂R ⁷⁵,-NHS (O) ₂R ⁷⁵, perhaps

W ⁶Be oxetanyl, tetrahydrofuran base, THP trtrahydropyranyl, oxepane alkyl, azetidinyl, pyrrolidyl, piperidyl, six hydrogen azepine _ base, Thietane base, thiacyclopentane base, tetrahydro thiapyran base, thia suberane base, 1,4-oxathiane base, 1,3-dioxolane base, 1,2-dithiolane base, 1,3-dithiolane base, six hydrogen-pyridazinyl, imidazolidyl, 1,3-two _ alkyl, morpholinyl, 1,3-dithiane base, 1,4-two _ alkyl, 1,4-dithiane base or parathiazan base, wherein R ⁷⁵And R ⁷⁶Be defined as implementing mode A1.

Embodiment A272. is according to the compound of embodiment A270, wherein

W ⁶Be-O-R ⁷⁵,-C (O) O-R ⁷⁵,-C (O)-R ⁷⁵,-NR ⁷⁵R ⁷⁶,-NHCH ₂C (O) R ⁷⁵,-NHC (O) R ⁷⁵,-S (O) ₂R ⁷⁵,-NHS (O) ₂R ⁷⁵, perhaps

W ⁶Be THP trtrahydropyranyl, oxepane alkyl, piperidyl, six hydrogen azepine _ base, tetrahydro thiapyran base, thia suberane base, 1,4-oxathiane base, morpholinyl, 1,4-two _ alkyl, 1,4-dithiane base or thio-morpholinyl, wherein R ⁷⁵And R ⁷⁶Be defined as implementing mode A1.

Embodiment A273. is according to the compound of embodiment A272, wherein

W ⁶Be-O-R ⁷⁵,-C (O) O-R ⁷⁵,-C (O)-R ⁷⁵,-NR ⁷⁵R ⁷⁶,-NHCH ₂C (O) R ⁷⁵,-NHC (O) R ⁷⁵,-S (O) ₂R ⁷⁵,-NHS (O) ₂R ⁷⁵, perhaps

W ⁶Be THP trtrahydropyranyl, piperidyl, tetrahydro thiapyran base or morpholinyl, wherein R ⁷⁵And R ⁷⁶Be defined as implementing mode A1.

Embodiment A274. is according to the compound of embodiment A273, wherein

W ⁶Be-O-R ⁷⁵,-C (O) O-R ⁷⁵,-NR ⁷⁵R ⁷⁶,-NHC (O) R ⁷⁵,-S (O) ₂R ⁷⁵, or

W ⁶Be THP trtrahydropyranyl, piperidyl, tetrahydro thiapyran base or morpholinyl, wherein R ⁷⁵And R ⁷⁶Be defined as implementing mode A1.

Embodiment A275. is according to the compound of embodiment A274, wherein

W ⁶Be-O-R ⁷⁵Or-C (O) O-R ⁷⁵, R wherein ⁷⁵Be defined as implementing mode A1.

Embodiment A276. is according to the compound of embodiment A275, wherein

W ⁶Be-C (O) O-R ⁷⁵, R wherein ⁷⁵Be defined as implementing mode A1.

Embodiment A277. is according to embodiment A1 to A230 or any one compound of A259 to A276, wherein

R ⁷⁵And R ⁷⁶Be independently selected from hydrogen ,-OH or optional quilt-NH ₂The C that replaces _1-6-alkyl.

Embodiment A278. is according to the compound of embodiment A277, wherein

R ⁷⁵And R ⁷⁶Be independently selected from hydrogen ,-OH or methyl.

Embodiment A279. is according to the compound of embodiment A278, wherein

R ⁷⁵And R ⁷⁶Be independently selected from hydrogen or-OH.

Embodiment A280. is according to the compound of embodiment A279, wherein

R ⁷⁵Be hydrogen.

Embodiment A281: the compound any according to embodiment A1 to A280, when testing under the glucose concn at 2mM, in glucokinase activation determination method disclosed herein (I), this compound is the activator of glucokinase.

Embodiment A282: the compound any according to embodiment A1 to A281, when when testing under 10 to 15mM the glucose concn, in glucokinase activation determination method disclosed herein (I), this compound is the activator of glucokinase.

Embodiment A283: the compound any according to embodiment A1 to A282, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the compound concentration of 30 μ M.

Embodiment A284: the compound any according to embodiment A1 to A283, under 10 to 15mM the glucose concn, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the compound concentration of 30 μ M.

Embodiment A285: the compound any according to embodiment A1 to A284, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the compound concentration of 5 μ M.

Embodiment A286: the compound any according to embodiment A1 to A285, under 10 to 15mM the glucose concn, in glucokinase activation determination method disclosed herein (I), this compound can provide at least 1.5 times, for example at least 1.7 times, at least 2.0 times glucokinase activation for example under the compound concentration of 5 μ M.

Embodiment A287: a kind of glucokinase activators compound, it is defined as a kind of like this compound, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound is measured high 1.5 times when producing under the glucose concn of glucokinase specific activity at 2mM, in glucokinase activation determination method (I) this compound not under 30 μ M or the lower compound concentration, and wherein the increase of the glucokinase activity that is provided by this compound increases and increases along with glucose concn.

Embodiment A288: the compound any according to embodiment A1 to A286, this compound provides the increase of glucokinase activity, and wherein the increase of the glucokinase activity that is provided by this compound increases along with the increase of glucose concn.

Embodiment A289: according to the compound of embodiment A287 or embodiment A288, under the glucose concn of 15mM, in glucokinase activation determination method disclosed herein (I), this compound provides the increase of glucokinase activity, and wherein the increase in the glucokinase activity that is provided by this compound under the glucose concn of 5mM, in glucokinase activation determination method disclosed herein (I) is provided in this increase.

Embodiment A290: the compound any according to embodiment A287 to A289, under the glucose concn of 15mM, in glucokinase activation determination method disclosed herein (I), this compound provides the increase of glucokinase activity under the compound concentration of 10 μ M, wherein the increase in the glucokinase activity that is provided under the compound concentration of 10 μ M by this compound under the glucose concn of 5mM, in glucokinase activation determination method disclosed herein (I) is provided in this increase.

Embodiment A291: the compound any according to embodiment A287 to A290, under the glucose concn of 15mM, in glucokinase activation determination method disclosed herein (I), this compound provides the increase of glucokinase activity under the compound concentration of 10 μ M, this increases than under the glucose concn of 5mM, at least 1.1 times of the increase height of the glucokinase activity that in glucokinase activation determination method disclosed herein (I), is provided under the compound concentration of 10 μ M by this compound, for example at least 1.2 times, for example at least 1.3 times, for example at least 1.4 times, for example at least 1.5 times, for example at least 1.6 times, for example at least 1.7 times, for example at least 1.8 times, for example at least 1.9 times, for example at least 2.0 times.

Embodiment A292: a kind of glucokinase activators compound, it is defined as a kind of like this compound, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound is under the glucose concn of glucokinase specific activity at 2mM that produces under 30 μ M or the lower compound concentration, measured not high 1.5 times during this compound in glucokinase activation determination method (I), this glucokinase activators compound increases the glucose utilization in the liver, and does not induce insulin secretion in response to glucose any increase to be arranged.

Embodiment A293: a kind of glucokinase activators compound, it is defined as a kind of like this compound, under the glucose concn of 2mM, in glucokinase activation determination method disclosed herein (I), this compound is not measured high 1.5 times during this compound under the glucose concn of glucokinase specific activity at 2mM that produces under 30 μ M or the lower compound concentration, in glucokinase activation determination method (I), this glucokinase activators compound in the liver cell that separates than in the Ins-1 cell, showing significantly higher activity.

Embodiment A294: the compound any according to embodiment A1 to A291, this compound increases the glucose utilization in the liver, and does not induce insulin secretion in response to glucose any increase to be arranged.

Embodiment A295: the compound any according to embodiment A1 to A291, this compound ratio in the liver cell that separates shows significantly higher activity in the Ins-1 cell.

Embodiment A296: the compound any according to embodiment A292 to A295, ratio shows significantly higher activity in the liver cell that this compound is separating when measuring described in glucokinase activation measurement (II) in the Ins-1 cell when measuring described in glucokinase activation measurement (III).

Embodiment A297: according to the compound of embodiment A296, this compound shows active in the liver cell of the separation of measurement as described in glucokinase activation measurement (II), at least 1.1 times of the active height of this compound of this specific activity in the Ins-1 cell of measurement as described in glucokinase activation measurement (III), for example at least 1.2 times, for example at least 1.3 times, for example at least 1.4 times, for example at least 1.5 times, for example at least 1.6 times, for example at least 1.7 times, for example at least 1.8 times, for example at least 1.9 times, for example at least 2.0 times, for example at least 3.0 times, for example at least 4.0 times, for example at least 5.0 times, for example at least 10 times.

Embodiment A298: according to the compound of embodiment A296, this compound shows in the Ins-1 cell of measurement as described in glucokinase activation measurement (III) does not have activity.

Embodiment A299: prevent hypoglycemic method, comprise the administration according to any one compound of embodiment A1 to A298.

Embodiment A300: the purposes of preventing hypoglycemic medicine to any one compound of embodiment A298 according to embodiment A1.

Embodiment A301: the compound any according to embodiment A1 to A298, it is the medicine that can be used for treating the indication that is selected from down group: hyperglycemia, IGT, insulin resistance syndrome, X syndrome, diabetes B, type 1 diabetes, hyperlipemia, hypertension and obesity.

Embodiment A302: as the medicinal compound any according to embodiment A1 to A301.

Embodiment A303: the compound any according to embodiment A1 to A301 is used for the treatment of the secretion that hyperglycemia, treatment IGT, treatment X syndrome, treatment diabetes B, treatment type 1 diabetes, treatment hyperlipemia, treatment hyperlipemia, treatment hypertension, treatment are fat, reduce ingestion of food, be used for appetite stimulator, be used for regulating feeding behavior or be used for strengthening incretin, for example GLP-1.

Embodiment A304. pharmaceutical composition, comprise at least a according to any one compound of embodiment A1 to 303 as activeconstituents, and one or more pharmaceutically acceptable carrier or vehicle.

Embodiment A305. is according to the presented in unit dosage form of the pharmaceutical composition of embodiment A304, wherein comprises about 0.05mg to about 1000mg, preferred extremely about 500mg, especially preferred about 0.5mg about 200mg compound any according to embodiment A1 to 303 extremely of about 0.1mg.

Embodiment 306. increases the purposes of glucokinase activity according to any one compound of embodiment A1 to 303.

Embodiment 306. is according to the purposes of any one the compound medicine of embodiment A1 to 303, and this medicine is used for the treatment of metabolic disturbance, reduce blood-glucose, the treatment hyperglycemia, treatment IGT, the treatment X syndrome, the treatment fasting glucose lowers (IFG), the treatment diabetes B, the treatment type 1 diabetes, delay glucose tolerance impaired (IGT) progress is diabetes B, delay non-insulin demand type diabetes B progress and be insulin requirements type diabetes B, the treatment hyperlipemia, the treatment hyperlipemia, treatment hypertension, reduce ingestion of food, be used for appetite stimulator, treatment is fat, regulate feeding behavior or strengthen the incretin secretion.

Embodiment A308. is according to the purposes of any one the compound medicine of embodiment A1 to 303, and this medicine is used for the assisting therapy of type 1 diabetes, with the generation of prevent diabetes complication.

Embodiment A309. is according to the purposes of any one the compound medicine of embodiment A1 to 303, and this medicine is for increasing quantity and/or the size of β cell in the mammalian subject; Be used for the treatment of the β cytopathy, particularly the apoptosis of β cell; Perhaps be used for the treatment of functional dyspepsia, particularly irritable bowel syndrome.

The purposes of compound in a kind of system that embodiment A310. is any one according to embodiment A307 to A309, this system comprise with other antidiabetic treatments.

The purposes of compound in a kind of system that embodiment A311. is any one according to embodiment A307 to A310, this system comprise with other hyperlipidemia agent treatments.

The purposes of compound in a kind of system that embodiment A312. is any one according to embodiment A307 to A311, this system comprise with other antiobesity agent treatments.

The purposes of compound in a kind of system that embodiment A313. is any one according to embodiment A307 to A312, this system comprise with other hypotensive agent treatments.

Embodiment A314. is used for the treatment of metabolic disturbance according to any one compound of embodiment A1 to A303 or according to the purposes of the pharmaceutical composition of embodiment A304 or embodiment A305, reduce blood-glucose, the treatment hyperglycemia, treatment IGT, the treatment X syndrome, the treatment fasting glucose lowers (IFG), the treatment diabetes B, the treatment type 1 diabetes, delay glucose tolerance impaired (IGT) progress is diabetes B, delay non-insulin demand type diabetes B progress and be insulin requirements type diabetes B, the treatment hyperlipemia, the treatment hyperlipemia, treatment hypertension, reduce ingestion of food, be used for appetite stimulator, treatment or prevention of obesity, regulate feeding behavior or strengthen the incretin secretion.

Embodiment A315. is used for the assisting therapy of type 1 diabetes, with the generation of prevent diabetes complication according to any one compound of embodiment A1 to A303 or according to the purposes of the pharmaceutical composition of embodiment A304 or embodiment A305.

Embodiment A316. is according to any one compound of embodiment A1 to A303 or according to the purposes of the pharmaceutical composition of embodiment A304 or embodiment A305, for increasing quantity and/or the size of β cell in the mammalian subject; Be used for the treatment of the β cytopathy, particularly the apoptosis of β cell; Perhaps be used for the treatment of functional dyspepsia, particularly irritable bowel syndrome.

Other embodiments are apparent from appended claims.

Be included in the scope of the present invention be by indivedual enantiomorphs of the compound of following formula (I) representative with and racemic mixture wholly or in part arbitrarily.The present invention also covers by indivedual enantiomorphs of the compound of following formula (I) representative and the mixture of its diastereomer, reverses in wherein one or more three-dimensional centers.

The invention provides the glucose-sensitive glucokinase activating agents, such glucokinase activating agents just, general formula (I) for example, it is than higher active the increasing of glucokinase is provided under the low glucose concentrations.This should be regarded as meaning that then this glucose-sensitive glucokinase activating agents provides the increase of glucokinase activity when glucose concn is low, and the increase of the glucokinase activity that is provided by this compound when glucose concn is higher is provided in this increase.This compound for example can provide 4.0 times glucokinase active increase under the glucose concn of 5mM, 2.0 times active the increasing of glucokinase is provided under the glucose concn of 15mM, thereby the increase of glucokinase activity is provided under the glucose concn of 5mM, this increase than the glucokinase that under the glucose concn of 15mM, is provided by this compound active increase high 2.0 times.For describing purpose of the present invention, can utilize glucokinase activation measurement (I) to measure glucose-sensitive, wherein under different glucose concn, measure the activity of glucokinase activating agents.

The glucose-sensitive of glucokinase activating agents for example can be measured like this, under the glucose concn of 5mM and under the glucose concn at 15mM, uses the glucokinase activating agents of same concentrations, for example the concentration of 10 μ M.Can compare this two observed values then, if at the active multiple under the glucose concn (than low glucose concentrations) of 5mM---be 4.0 times in last example---being significantly higher than the active multiple under the glucose concn (higher glucose concentrations) at 15mM---in last example be 2.0 times, this glucokinase activating agents is considered to a kind of glucose-sensitive glucokinase activating agents so.In last example, active the increasing of the glucokinase under the glucose concn of 5mM increases high 2.0 times than the activity of the glucokinase under the glucose concn at 15mM.For example can be than at least 1.1 times of the active height of the glucokinase activating agents under 15mM glucose active the increasing of the glucokinase that is provided by this glucokinase activating agents under the 5mM glucose, for example at least 1.2 times, for example at least 1.3 times, for example at least 1.4 times, for example at least 1.5 times, for example at least 1.6 times, for example at least 1.7 times, for example at least 1.8 times, for example at least 1.9 times, for example at least 2.0 times.

The invention provides liver-specificity glucokinase activating agents, such glucokinase activating agents just, general formula (I) for example, their increase the glucose utilization (just increasing glycogen deposition) in liver, and do not induce insulin secretion in response to glucose any increase to be arranged.For describing purpose of the present invention, the potential liver selectivity of glucokinase activating agents can be measured like this, namely contrast in the liver cell that separates in response to this glucokinase activating agents gained result and in the Ins-1 cell in response to this glucokinase activating agents gained result.Glucokinase activating agents then is regarded as liver-specificity glucokinase activating agents if show that in the liver cell of the separation of measurement as described in glucokinase activation measurement (II) activity is significantly higher than the activity in the Ins-1 cell of measurement as described in glucokinase activation measurement (III).The activity of glucokinase activating agents in glucokinase activation measurement (II) (liver cell) for example can be than at least 1.1 times of the active height of this glucokinase activating agents in glucokinase activation measurement (III) (Ins-1 cell), for example at least 1.2 times, for example at least 1.3 times, for example at least 1.4 times, for example at least 1.5 times, for example at least 1.6 times, for example at least 1.7 times, for example at least 1.8 times, for example at least 1.9 times, for example at least 2.0 times, for example at least 3.0 times, for example at least 4.0 times, for example at least 5.0 times, for example at least 10 times.Select as an alternative, glucokinase activating agents can show there is not activity in the Ins-1 cell of measurement as described in glucokinase activation measurement (III), and shows significant active in the liver cell of measurement as described in glucokinase activation measurement (II).

This class liver-specificity glucokinase activating agents can be used for facing the patient of experience hypoglycemia danger especially.Because the liver glucokinase is highstrung to serum glucose concentration, the blood-glucose of GK reduces effect with only generation when serum glucose concentration is higher relatively in the liver.When serum glucose concentration was relatively low, the effect of GK reduced in the liver, thereby can further not reduce the glucose concn in the blood.Even liver GK is subjected to the influence of GK activator, also keep this mechanism.The effect of the pancreas β of GK cell is not similar glucose-susceptibility.Therefore, may under low serum glucose concentration, also have glucose-reduction effect even both influenced liver and also influence the GK activator of β cell, cause hypoglycemic danger.Only influence or mainly influence the GK activator of liver GK thereby will when treatment is provided, have lower hypoglycemia danger.Thereby, the invention provides the hypoglycemic method of prevention, comprise the administration of liver-specificity glucokinase activating agents, and liver-specificity glucokinase activating agents is for the preparation of the purposes of the hypoglycemic medicine of prevention.

The example of liver-specificity glucokinase activating agents has

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's ethyl ester

(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) acetic acid ethyl ester (embodiment 110),

(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) acetic acid (embodiment 111),

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid (embodiment 112),

2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl)-N-(2-morpholine-4-base ethyl) ethanamide (embodiment 118),

[2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) kharophen] acetic acid (embodiment 121),

{ 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } acetic acid (embodiment 144) and

2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid (embodiment 154).

In one embodiment, according to the medicine of compound of the present invention as the treatment hyperglycemia.

In one embodiment, according to the medicine of compound of the present invention as treatment IGT.

In one embodiment, according to the medicine of compound of the present invention as the treatment X syndrome.

In one embodiment, according to the medicine of compound of the present invention as the treatment diabetes B.

In one embodiment, according to the medicine of compound of the present invention as the treatment type 1 diabetes.

In one embodiment, according to the medicine of compound of the present invention as the treatment hyperlipemia.

In one embodiment, according to the medicine of compound of the present invention as the treatment hyperlipemia.

In one embodiment, be used as the hypertensive medicine for the treatment of according to compound of the present invention.

In one embodiment, according to the medicine of compound of the present invention as the treatment obesity.

In one embodiment, according to the medicine of compound of the present invention as the reduction ingestion of food.

In one embodiment, according to the medicine of compound of the present invention as appetite stimulator.

In one embodiment, according to the medicine of compound of the present invention as the adjusting feeding behavior.

In one embodiment, according to the medicine of compound of the present invention as enhancing incretin, for example GLP-1 secretion.

The compounds of this invention is glucokinase activating agents, itself can be used for the activation of glucokinase.

Therefore, the invention provides the method that activates glucokinase in the patient of needs, this method comprises gives according to compound of the present invention the curee that these needs are arranged, and dosage is preferably on the pharmacology and effectively measures, and more preferably effectively measures on the therapeutics.The present invention also is provided at the method that reduces blood-glucose among the patient who needs, and this method comprises gives according to compound of the present invention the curee that these needs are arranged, and dosage is preferably on the pharmacology and effectively measures, and more preferably effectively measures on the therapeutics.The present invention also provides the method for the human diseases that prevents and/or treats glucokinase defective-mediation, this method comprise to the people that these needs are arranged give significant quantity on the therapeutics according to compound of the present invention.Wording used herein " has the curee who needs " and comprises mammalian subject, and preferred human, it suffers from one or more above-mentioned disease or morbid states, perhaps faces such danger.Therefore, in methods for the treatment of background of the present invention, this method also comprises method preventative or treatment mammalian subject before diagnosing out this class disease or morbid state.

In one embodiment, the invention provides the treatment hyperglycemia method, this method comprise to the curee that these needs are arranged give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the invention provides the treatment IGT method, this method comprise to the curee that these needs are arranged give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the invention provides the treatment X syndrome method, this method comprise to the curee that these needs are arranged give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the invention provides the treatment diabetes B method, this method comprise to the curee that these needs are arranged give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the invention provides the treatment type 1 diabetes method, this method comprise to the curee that these needs are arranged give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the invention provides the method for the treatment of hyperlipemia or hyperlipemia, this method comprise curee to needs give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the invention provides the fat method for the treatment of, this method comprise curee to needs give significant quantity according to compound of the present invention or pharmaceutical composition.

In one embodiment, the significant quantity of compound at about 0.05mg to the scope of about 2000mg, preferred about 0.1mg about 1000mg extremely, the especially preferably extremely about 500mg of about 0.5mg every day.

In one embodiment, the method according to this invention is an a kind of part of system, this system comprises with the treatment of other antidiabetics, and described antidiabetic is Regular Insulin or insulin analog, sulfonylurea, biguanides, meglitinide, insulin sensitizers, thiazolidinedione insulin sensitizers, alpha-glucosidase inhibitor, glycogen phosphorylase inhibitors or act on the reagent of the ATP-dependency potassium channel of pancreas beta cell for example.

In one embodiment, the method according to this invention is an a kind of part of system, this system comprises with other hyperlipidemia agent treatments, and described hyperlipidemia agent is Colestyramine, colestipol, chlorine Bei Te, gemfibrozil, lovastatin, Pravastatin, Simvastatin, probucol or dextrothyroxine for example.

In one embodiment, the method according to this invention is an a kind of part of system, and this system comprises with other antiobesity agents or appetite stimulator treatment.

In one embodiment, the method according to this invention is an a kind of part of system, and this system comprises with other hypotensive agent treatments.

Other embodiments of these class methods will be apparent from following explanation.

Compound according to the present invention can be used for treating wherein, and the glucokinase activation is useful obstacle, disease and illness.

Therefore, The compounds of this invention can be used for treating hyperglycemia, IGT (glucose tolerance is impaired), insulin resistance syndrome, X syndrome, type 1 diabetes, diabetes B, hyperlipemia, dyslipoproteinemia (the unusual lipoprotein in the blood), comprise diabetic hyperlipemia, hyperlipemia, teinemia (lipoprotein in the blood is too much), comprise I type, II-a type (hypercholesteremia), II-b type, III type, IV type (hypertriglyceridaemia) and V-type (hypertriglyceridaemia) teinemia and obesity.In addition, they can be used for the treatment of proteinuria; Cardiovascular disorder, for example megalocardia, hypertension and arteriosclerosis comprise atherosclerosis; Gastrointestinal disorders; Acute pancreatitis; With appetite stimulator or energy expenditure obstacle.

Therefore, on the other hand, the present invention relates to as medicinal according to compound of the present invention.

The present invention also relates to pharmaceutical composition, comprise at least a compound according to the present invention as activeconstituents, and one or more pharmaceutically acceptable carrier or vehicle.

Pharmaceutical composition is presented in unit dosage form preferably, comprise about 0.05mg to about 1000mg, preferably about 0.1mg extremely about 500mg, especially preferably about 0.5mg extremely about 200mg according to compound of the present invention.

In one embodiment, pharmaceutical composition according to the present invention comprises other antidiabetics, and described antidiabetic is Regular Insulin, insulins derivative or insulin analog, sulfonylurea, biguanides, meglitinide, insulin sensitizers, thiazolidinedione insulin sensitizers, alpha-glucosidase inhibitor, glycogen phosphorylase inhibitors or act on the reagent of the ATP-dependency potassium channel of pancreas beta cell for example.

In one embodiment, pharmaceutical composition according to the present invention comprises other hyperlipidemia agent, and described hyperlipidemia agent is Colestyramine, colestipol, chlorine Bei Te, gemfibrozil, lovastatin, Pravastatin, Simvastatin, probucol or dextrothyroxine for example.

In one embodiment, pharmaceutical composition according to the present invention comprises other antiobesity agents or appetite stimulator.

In one embodiment, pharmaceutical composition according to the present invention comprises other hypotensive agents.

In one embodiment of the invention, pharmaceutical composition according to the present invention comprises the combination according to compound of the present invention and one or more reagent above-mentioned, for example the combination of metformin and sulfonylurea (for example Glyburide (glyburide)); The combination of sulfonylurea and acarbose; The combination of nateglinide and metformin; The combination of acarbose and metformin; The combination of sulfonylurea, metformin and troglitazone; The combination of Regular Insulin and sulfonylurea; The combination of Regular Insulin and metformin; The combination of Regular Insulin, metformin and sulfonylurea; The combination of Regular Insulin and troglitazone; The combination of Regular Insulin and lovastatin etc.

In one embodiment of the invention, The compounds of this invention is for the preparation of the medicine for the treatment of hyperglycemia.Hyperglycemia used herein be this area general understand, for example with reference to theReport of the Expert Committee of the Diagnosis andClassification of Diabetes Mellitus, be published in Diabetes Care 20,1183-1197, (1997) in, but the ordinary representation plasma glucose levels raises above about 110mg/dl.The compounds of this invention effectively reduces on an empty stomach and the blood-glucose in stage after meal.

In one embodiment of the invention, The compounds of this invention is for the preparation of the pharmaceutical composition for the treatment of IGT.

In one embodiment of the invention, The compounds of this invention is for the preparation of the pharmaceutical composition for the treatment of X syndrome.

In one embodiment of the invention, The compounds of this invention is for the preparation of the pharmaceutical composition for the treatment of diabetes B.It is diabetes B and to delay non-insulin demand type diabetes B progress be that insulin requirements type diabetes B is the treatment of purpose that the treatment of this class comprises delaying the IGT progress.

In one embodiment of the invention, The compounds of this invention is for the preparation of the pharmaceutical composition for the treatment of type 1 diabetes.This class therapy is under normal circumstances with insulin administration.

In one embodiment of the invention, The compounds of this invention is for the preparation of the pharmaceutical composition for the treatment of hyperlipemia and hyperlipemia.

In one embodiment of the invention, The compounds of this invention is for the preparation of the fat pharmaceutical composition for the treatment of.

In another aspect of this invention, with The compounds of this invention the treatment that the patient carries out is combined with diet and/or exercise.

The invention provides the method that activates Mammals glucokinase activity, this method comprise to the Mammals that needs the active activation of glucokinase give limited amount on the therapeutics as defined above according to compound of the present invention, the crystallized form of or multiform single for it, amorphous, single enantiomorph, racemic mixture, single steric isomer, the mixture of steric isomer, single diastereomer, mixture, pharmacy acceptable salt, solvate, prodrug, biological hydrolyzable ester or the biological hydrolyzable acid amides of diastereomer.

The invention provides the method that activates glucokinase, comprise the step according to compound of the present invention of the Mammals that these needs are arranged being given significant quantity on the pharmacology.The present invention further provides pharmaceutical composition, wherein comprise significant quantity on pharmaceutically acceptable carrier and the pharmacology according to compound of the present invention, present in an amount at least sufficient to activate glucokinase.Glucokinase-activation amount can be to reduce or suppress the amount of PTP enzymic activity among the curee.

In addition by provided by the present invention be pharmaceutical composition, comprise significant quantity on pharmaceutically acceptable carrier and the pharmacology according to compound of the present invention, be enough to treat type i diabetes.

Also by provided by the present invention be pharmaceutical composition, comprise significant quantity on pharmaceutically acceptable carrier and the pharmacology according to compound of the present invention, be enough to treat type ii diabetes.

The compounds of this invention can be to any Mammals administration that needs the active activation of glucokinase.This class Mammals for example can comprise horse, ox, sheep, pig, mouse, dog, cat, primates, and for example chimpanzee, gorilla (gorillas), macaque are most preferably human.

In another aspect of this invention, other active substances of The compounds of this invention and one or more are in being fit to the ratio Combined Preparation arbitrarily.Other active agents of this class can be selected from antidiabetic, hyperlipidemia agent, antiobesity agent, hypotensive agent and by the therapeutical agent of complications associated with arterial system due to the diabetes or with it.

The antidiabetic that is fit to comprises Regular Insulin; GLP-1 (glucagon-like-peptide-1) derivative for example is disclosed among the WO 98/08871 (Novo Nordisk A/S) those, quotes at this as a reference; And Orally active Hypoylycemic agents.

The Orally active Hypoylycemic agents that is fit to preferably include imidazolines, sulfonylurea, biguanides, meglitinide, _ oxazolidinedione, thiazolidinedione, insulin sensitizers, alpha-glucosidase inhibitor, act on the reagent of the ATP-dependency potassium channel of pancreas beta cell, potassium channel openers for example, for example be disclosed among WO 97/26265, WO 99/03861 and the WO 00/37474 (NovoNordisk A/S) those, quote at this as a reference; Potassium channel openers, for example ormitiglinide; Potassium channel antagonists, for example nateglinide or BTS-67582; Glucagon antagonist, for example be disclosed in WO 99/01423 and WO 00/39088 (NovoNordisk A/S and Agouron Pharmaceuticals, Inc.) in those are quoted at this as a reference; The GLP-1 agonist, for example be disclosed in WO 00/42026 (NovoNordisk A/S and Agouron Pharmaceuticals, Inc.) in those are quoted at this as a reference; DPP-IV (dipeptidyl peptidase-IV) inhibitor, PTP enzyme (Protein-tyrosine-phosphatase) inhibitor, the inhibitor of the liver enzyme that involved in sugar heteroplasia and/or glycogenolysis stimulate, the glucose uptake adjusting control agent, GSK-3 (glycogen synthase kinase-3) inhibitor, change the compound (for example hyperlipemia agent and hyperlipemia agent) of lipid metabolism, reduce the compound of ingestion of food, PPAR (peroxisome proliferation-activated receptor) and RXR (retinoid X acceptor) agonist (ALRT-268 for example, LG-1268 or LG-1069).

In one embodiment of the invention, The compounds of this invention and Regular Insulin, insulin derivates or insulin analog Combined Preparation.

In one embodiment of the invention, The compounds of this invention and a kind of sulfonylurea Combined Preparation, for example tolbutamide, P-607, tolazamide, Glyburide (glibenclamide), Glipizide, glimepiride, gliclazide or Glyburide (glyburide).

In one embodiment of the invention, The compounds of this invention and a kind of biguanides Combined Preparation, for example metformin.

In one embodiment of the invention, The compounds of this invention and a kind of meglitinide Combined Preparation, for example repaglinide or senaglinide/nateglinide.

In one embodiment of the invention, The compounds of this invention and thiazolidinedione insulin sensitizers Combined Preparation, for example troglitazone, Xi Gelie ketone, pioglitazone, rosiglitazone, Yi Gelie ketone, darglitazone, englitazone, CS-011/CI-1037 or T174 or be disclosed in compound among WO 97/41097 (DRF-2344), WO 97/41119, WO 97/41120, WO 00/41121 and the WO 98/45292 (Dr.Reddy ' s Research Foundation) quote at this as a reference.

In one embodiment of the invention, The compounds of this invention can with a kind of insulin sensitizers Combined Preparation, for example GI 262570, YM-440, MCC-555, JTT-501, AR-H039242, KRP-297, GW-409544, CRE-16336, AR-H049020, LY510929, MBX-102, CLX-0940, GW-501516 or be disclosed in WO 99/19313 (NN622/DRF-2725), WO 00/50414, WO 00/63191, WO 00/63192, WO00/63193 (Dr.Reddy ' s Research Foundation), WO 00/23425, WO00/23415, WO 00/23451, WO 00/23445, WO 00/23417, WO 00/23416, WO 00/63153, WO 00/63196, WO 00/63209, compound among WO 00/63190 and the WO 00/63189 (Novo Nordisk A/S) is quoted at this as a reference.

In one embodiment of the invention, The compounds of this invention and a kind of alpha-glucosidase inhibitor Combined Preparation, for example voglibose, emiglitate, miglitol or acarbose.

In one embodiment of the invention, The compounds of this invention and a kind of glycogen phosphorylase inhibitors Combined Preparation for example are described in the compound among the WO 97/09040 (Novo Nordisk A/S).

In one embodiment of the invention, The compounds of this invention is with a kind of reagent Combined Preparation of the ATP-dependency potassium channel that acts on the pancreas beta cell, for example tolbutamide, Glyburide (glibenclamide), Glipizide, gliclazide, BTS-67582 or repaglinide.

In one embodiment of the invention, The compounds of this invention and nateglinide Combined Preparation.

In one embodiment of the invention, The compounds of this invention and a kind of hyperlipidemia agent or hyperlipemia agent Combined Preparation, for example Colestyramine, colestipol, chlorine Bei Te, gemfibrozil, lovastatin, Pravastatin, Simvastatin, probucol or dextrothyroxine.

In another aspect of this invention, The compounds of this invention is and more than one above-claimed cpd Combined Preparation, for example metformin and sulfonylurea (for example Glyburide (glyburide)); Sulfonylurea and acarbose; Nateglinide and metformin; Acarbose and metformin; Sulfonylurea, metformin and troglitazone; Regular Insulin and sulfonylurea; Regular Insulin and metformin; Regular Insulin, metformin and sulfonylurea; Regular Insulin and troglitazone; Regular Insulin and lovastatin etc.

In addition, according to compound of the present invention can with one or more antiobesity agents or appetite stimulator Combined Preparation.

This class reagent can be selected from down group: CART (transcribing of Cocaine amphetamine adjusting) agonist, NPY (neuropeptide tyrosine) antagonist, MC3 (melanocortin 3) agonist, MC4 (melanocortin 4) agonist, the orexin antagonist, TNF (tumour necrosis factor) agonist, CRF (corticotropin releasing factor (CRF)) agonist, CRF BP (corticotropin releasing factor (CRF) is in conjunction with albumen) antagonist, Urocortin (urocortin) agonist, 'beta '3 adrenergic agonists (CL-316243 for example, AJ-9677, GW-0604, LY362884, LY377267 or AZ-40140), MSH (melanophore-stimulation hormone) agonist, MCH (melanophore-enrichment hormone) antagonist, CCK (cholecystokinin) agonist, serotonin reuptake inhibitors (fluoxetine, seroxat or citalopram), thrombotonin and NRI, 5HT (thrombotonin) agonist, the bombesin agonist, the galanin antagonist, tethelin, somatomedin (for example prolactin antagonist or galactagogin), growth hormone releasing compounds, TRH (thyrotrophin-releasing hormone) agonist, UCP2 or 3 (uncoupling protein 2 or 3) adjusting control agent, RMETHU LEPTIN (leptin) agonist, DA (Dopamine HCL) agonist (bromocriptine, doprexin), lipase/amylase inhibitor, the PPAR adjusting control agent, the RXR adjusting control agent, the TR beta-agonists, adrenergic CNS stimulant, AGRP (agouti associated protein) inhibitor, the H3 histamine antagonist (for example is described in WO 00/42023, among WO 00/63208 and the WO 00/64884 those are quoted at this as a reference), exendin-4, GLP-1 agonist and ciliary neurotrophic factor.Other antiobesity agents have Bupropion (antidepressive), topiramate (anticonvulsive agent), ecopipam (dopamine D 1/D5 antagonist) and TREXUPONT (OPIOIDS antagonist).

In one embodiment of the invention, antiobesity agent is RMETHU LEPTIN.

In one embodiment of the invention, antiobesity agent is thrombotonin and NRI, for example sibutramine.

In one embodiment of the invention, antiobesity agent is lipase inhibitor, for example orlistat.

In one embodiment of the invention, antiobesity agent is adrenergic CNS stimulant, for example Dextroamphetamine, amphetamine, phentermine, Mazindol, phendimetrazine, Diethylpropion, Phenfluoramine or Isomeride.

In addition, The compounds of this invention can with one or more hypotensive agent Combined Preparation.The example of hypotensive agent has beta-Blocking agent, for example alprenolol, atenolol USP 23, timolol, pindolol, Proprasylyte and metoprolol; ACE (angiotensin-converting enzyme) inhibitor, for example benazepril, captopril, enalapril, fosinopril, lisinopril, quinapril and Ramipril; Calcium channel blocker, for example nifedipine, felodipine, nicardipine, Isradipine, nimodipine, diltiazem _ and verapamil; And α-Zu Zhiji, for example Doxazosin, urapidil, Prazosin and terazosin.Can be with further reference to Remington:The Science and Practice of Pharmacy, 19thEdition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995.

On the other hand, the invention provides pharmaceutical preparations, wherein comprise glucokinase activating agents and insulin derivates.

In one embodiment of the invention, insulin derivates is selected from down group: B29-N ⁸-mnyristoyl-des (B30) insulin human, B29-N ^ε-palmityl-des (B30) insulin human, B29-N ^ε-mnyristoyl insulin human, B29-N ^ε-palmityl insulin human, B28-N ⁸-mnyristoyl Lys ^B28Pro ^B29Insulin human, B28-N ^ε-palmityl Lys ^B28Pro ^B29Insulin human, B30-N ^ε-mnyristoyl-Thr ^B29Lys ^B30Insulin human, B30-N ^ε-palmityl-Thr ^B29Lys ^B30Insulin human, B29-N ^ε-(N-palmityl-gamma-glutamyl)-des (B30) insulin human, B29-N ^ε-(N-stone courage acyl-gamma-glutamyl)-des (B30) insulin human, B29-N ^ε-(ω-carboxyl heptadecanoyl)-des (B30) insulin human and B29-N ^ε-(ω-carboxyl heptadecanoyl) insulin human.

In another embodiment of the invention, insulin derivates is B29-N ^ε-mnyristoyl-des (B30) insulin human.

Should be appreciated that according to compound of the present invention and diet and/or exercise, one or more above-claimed cpds and optionally the combination that is fit to arbitrarily of one or more other active substances all be regarded as within the scope of the invention.

Pharmaceutical composition

The compounds of this invention can be individually dosed or with pharmaceutically acceptable carrier or vehicle Combined Preparation, divide single agent or multi-agent.Can prepare like this according to pharmaceutical composition of the present invention, namely according to routine techniques, for example be disclosed in Remington:The Science andPractice of Pharmacy, 19th Edition, Gennaro, Ed., MackPublishing Co., Easton, PA, in 1995 those use pharmaceutically acceptable carrier or thinner and other known auxiliary agents and vehicle carry out arbitrarily.

Pharmaceutical composition can specifically be mixed with for by being fit to arbitrarily administration, for example in oral, rectum, nose, lung, part (comprising oral cavity and hypogloeeis), transdermal, the brain pond, intraperitoneal, vagina and parenteral (comprise in subcutaneous, intramuscular, the sheath, intravenously and intradermal) approach, oral route is preferred.What will be understanded is that preferred approach will depend on curee's general condition and age, the sanatory attribute of institute and selected activeconstituents.

Be used for pharmaceutical composition for oral administration and comprise solid dosage, for example hard or soft capsule, tablet, dragee, dragee, pill, lozenge, pulvis and granule.In due course, they can have dressing, enteric coating for example, and perhaps they can be prepared like this according to method well known in the art, discharge with the control that activeconstituents is provided, for example the release that continues or prolong.

The liquid dosage form that is used for oral administration comprises solution, emulsion, water-based or oil-based suspension, syrup and elixir.

The pharmaceutical composition that is used for administered parenterally comprises aseptic water-based and non-aqueous Injectable solution, dispersion, suspension or emulsion, and aseptic pulvis, is regenerated as aseptic Injectable solution or dispersion before use.The Drug Storage injection formulations also covered in the scope of the present invention.

Other form of administration that are fit to comprise suppository, sprays, ointment, creme, gelifying agent, inhalation, skin patch, implant etc.

Typical oral dosage is about 0.001 to the about 100mg/kg body weight scope of every day, preferred about 0.01 to about 50mg/kg body weight every day, 0.05 to about 10mg/kg body weight every day more preferably from about, branch potion or multi-agent administration, for example 1 to 3 dose.Accurate dose will depend on the frequency of administration and mode, curee sex, age, body weight and general condition, the illness for the treatment of and apparent other factors of the disease accompanied attribute and seriousness and those skilled in the art for the treatment of.

By method known to those skilled in the art, preparation is the display unit dosage form aptly.Be used for every day one or repeatedly, for example every day 1 to 3 oral administration the typical unit dosage form can contain 0.05 to about 1000mg, preferred about 0.1 to about 500mg, 0.5mg about 200mg extremely more preferably from about.

With regard to parenteral route, for example in the intravenously, sheath, intramuscular and similar administration, typical dosage is the only about half of of the dosage that adopts of oral administration.

The compounds of this invention generally adopts dissociant or its pharmacy acceptable salt.Example has the acid salt of the compound with free alkali practicality and has the base addition salt of the compound of free acid practicality.The non-toxic salts of The compounds of this invention represented in term " pharmacy acceptable salt ", generally is to prepare like this, even free alkali and the organic or inorganic acid-respons that is fit to perhaps make sour with suitable organic or inorganic alkali reaction.When compound according to the present invention contained free alkali, this class salt prepared in a conventional manner, was about to the solution of compound or suspension with stoichiometric pharmaceutically acceptable acid treatment.When compound according to the present invention contained free acid, this class salt prepared in a conventional manner, was about to the solution of compound or suspension with stoichiometric pharmaceutically acceptable alkaline purification.Have negatively charged ion that acceptable salt on the physiology of compound of hydroxyl comprises described compound and be fit to cationic combination, for example sodium or ammonium ion.Other are not that pharmacy acceptable salt also can be for the preparation of The compounds of this invention, and these constitute another aspect of the present invention.

With regard to administered parenterally, can adopt the novel solution of formula (I) compound in aseptic aqueous solution, aqueous propylene glycol or sesame or peanut oil.If necessary, this class aqueous solution should suitably be cushioned, and liquid diluent is at first given isotonicity by capacity salt solution or glucose.The aqueous solution is particularly suitable for intravenously, intramuscular, subcutaneous and peritoneal injection.The sterile aqueous media that adopts all is to obtain for technology well known by persons skilled in the art easily.

The pharmaceutical carrier that is fit to comprises inert solid diluent or weighting agent, aseptic aqueous solution and various organic solvent.The example of solid carrier has lactose, carclazyte, sucrose, cyclodextrin, talcum, gelatin, agar, pectin, gum arabic, Magnesium Stearate, stearic acid and cellulosic lower alkyl ether.The example of liquid vehicle has syrup, peanut oil, sweet oil, phosphatide, lipid acid, fatty acid amine, polyoxyethylene and water.Similarly, carrier or thinner can comprise any lasting releasable material known in the art, and for example Zerol or Stearic diglyceride mix separately or with wax.The The compounds of this invention of novelty and pharmaceutically acceptable carrier are combined the pharmaceutical composition that constitutes then easily with the multiple formulation administration that is suitable for disclosed route of administration.By the known method of pharmaceutical field, preparation is the display unit dosage form aptly.

The preparation of the present invention that is suitable for oral administration can present discrete unit, and for example capsule or tablet contain the activeconstituents of predetermined amount separately, and can comprise suitable vehicle.In addition, oral preparations can be the form of pulvis or granule, the solution in water-based or non-aqueous liquid or suspension or oil-in-water-type or water-in-oil emulsion.

Oral composition can prepare according to any known process, and this based composition can contain one or more reagent that is selected from the group of being made up of sweeting agent, correctives, tinting material and sanitas, and purpose provides pharmaceutically good to eat prepared product attractive in appearance.Tablet can contain the mixture of activeconstituents and nontoxic pharmaceutically acceptable vehicle, and described vehicle is suitable for the preparation of tablet.These vehicle for example can be inert diluent, for example calcium carbonate, yellow soda ash, lactose, calcium phosphate or sodium phosphate; Granulation and disintegrating agent, for example W-Gum or alginic acid; Tackiness agent, for example starch, gelatin or gum arabic; And lubricant, for example Magnesium Stearate, stearic acid or talcum.Tablet can be not dressing or they can be by the known technology dressing, delaying disintegration and the absorption in gi tract, thereby provide continuous action for a long time.For example, can adopt a kind of time-delay material, for example Zerol or Stearic diglyceride.Also can utilize U.S. Patent No. 4,356,108,4,166,452 and 4,265, the described technology of 874 (quoting at this as a reference) is made the osmotic therapeutic sheet that discharges for control.

Mouth also can present hard-gelatin capsules with preparation, and wherein activeconstituents mixes with inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin; Perhaps Gelseal, wherein activeconstituents mixes with water or oily medium, for example peanut oil, whiteruss or sweet oil.

Aqueous suspension can contain the mixture of active compound and vehicle, and described vehicle is suitable for the preparation of aqueous suspension.This class vehicle has suspension agent, for example Xylo-Mucine, methylcellulose gum, Vltra tears, sodiun alginate, polyvinylpyrrolidone, tragacanth gum and gum arabic; Dispersion or wetting agent can be naturally occurring phosphatide, Yelkin TTS for example, the perhaps condensation product of alkylene oxide and lipid acid, polyoxyethylene stearic acid ester for example, the perhaps condensation product of ethylene oxide and long chain aliphatic alcohol, heptadecene oxygen base hexadecanol for example, the perhaps condensation product of ethylene oxide and the partial ester of deriving from lipid acid and hexitol, polyoxyethylene sorbitol monoleate for example, the perhaps condensation product of ethylene oxide and the partial ester of deriving from lipid acid and hexitan, for example polyoxyethylene sorbitan monooleate.Aqueous suspension also can contain one or more tinting materials, one or more correctivess and one or more sweeting agents, for example sucrose or asccharin.

Oil-based suspension can be prepared like this, is about to activeconstituents and is suspended in vegetables oil or the mineral oil, and described vegetables oil is peanut oil, sweet oil, sesame oil or Oleum Cocois for example, and described mineral oil is whiteruss for example.Oil-based suspension can contain thickening material, for example beeswax, paraffinum durum or hexadecanol.Can add sweeting agent, for example above-mentioned those, and correctives is to provide good to eat oral prepared product.Can to these compositions add antioxidants for example xitix carry out anticorrosion.

Dispersible pulvis and granule are suitable for adding water and prepare aqueous suspension, and the mixture of active compound and dispersion or wetting agent, suspension agent and one or more sanitass is provided.The dispersion that is fit to or wetting agent and suspension agent be already mentioned above those.Also can there be other vehicle, for example sweeting agent, correctives and tinting material.

Pharmaceutical composition of the present invention also can be the form of oil-in-water emulsion.Oil phase can be vegetables oil, for example sweet oil or peanut oil, perhaps mineral oil, for example whiteruss, or its mixture.The emulsifying agent that is fit to can be naturally occurring natural gum, for example gum arabic or tragacanth gum; Naturally occurring phosphatide, for example soybean phospholipid, Yelkin TTS and ester or the partial ester of deriving from lipid acid and hexitan, for example condensation product of polyoxyethylene-sorbitan mono-oleate and described partial ester and ethylene oxide, for example polyoxyethylene sorbitan monooleate.Emulsion also can contain sweeting agent and correctives.

Syrup and elixir can be prepared with sweeting agent, for example glycerine, propylene glycol, Sorbitol Powder or sucrose.This class preparation also can contain negative catalyst, sanitas and flavoring and tinting material.Pharmaceutical composition can be aseptic injectable water-based or the form of oil-based suspension.This suspension can be prepared according to currently known methods, uses above-mentioned suitable dispersion or wetting agent and suspension agent.Aseptic injectable prepared product also can be at nontoxic parenteral acceptable diluent or sterile injectable solution or the suspension in the solvent, for example solution in 1,3 butylene glycol.The acceptable carrier that can adopt and solvent have water, Ringer's solution and isotonic sodium chlorrde solution.In addition, aseptic expressed oil is solvent or the suspension medium of using always.For this reason, the expressed oil of any brand be can adopt, synthetic monoglyceride or triglyceride used.In addition, in the preparation of injection, can use lipid acid, for example oleic acid.

Composition also can be the form of suppository, is used for the rectal administration of The compounds of this invention.These compositions can prepare like this, are about to medicine and mix with the nonirritant excipient that is fit to, and described vehicle is solid at normal temperatures, but is liquid under rectal temperature, thereby will melt in rectum, discharges medicine.This class material for example comprises theobroma oil and polyoxyethylene glycol.

With regard to use the part, consider creme, ointment, jelly, solution or suspension etc., wherein contain compound of the present invention.For this application aims, topical application should comprise collutory and mouth wash shua.

The compounds of this invention also can be with the form administration of liposome delivery system, for example small-sized individual layer capsule, large-scale individual layer capsule and multilayer capsule.Liposome can be made from various phosphatide, for example cholesterol, stearylamine or phosphatidylcholine.

In addition, some The compounds of this invention can generate solvate with water or ordinary organic solvents.This kind solvent thing is also contained within the scope of the invention.

Thereby, pharmaceutical composition is provided in another embodiment, wherein comprise according to compound of the present invention or its pharmacy acceptable salt, solvate or prodrug and one or more pharmaceutically acceptable carriers, vehicle or thinner.

If use solid carrier to carry out oral administration, the prepared product compressing tablet can be placed hard gelatin capsule with powder or particle form, perhaps can be the form of dragee or lozenge.The amount of solid carrier will have nothing in common with each other, but will be about 25mg about 1g extremely usually.If use liquid vehicle, prepared product can be syrup, emulsion, Gelseal or aseptic injectable liquids form, for example water-based or non-aqueous liquid suspension or solution.

Can contain by the typical tablet of conventional pressed disc technique preparation:

The sheet heart:

Active compound (free cpds or its salt) 5.0mg

Lactose Ph.Eur. 67.8mg

Microcrystalline Cellulose (Avicel) 31.4mg

Amberlite_IRP88* 1.0mg

Magnesium Stearate Ph.Eur. q.s.

Dressing:

The about 9mg of Vltra tears

The about 0.9mg of Mywacett9-40T**

* Polarcrillin potassium NF, tablet disintegrant, Rohm and Haas.

* acidylate monoglyceride is as film clothing softening agent.

If necessary, pharmaceutical composition of the present invention can comprise the combination according to compound of the present invention and other active substances, for example mentioned above those.

The present invention also provides the method for the synthetic compound that can be used as formula (I) compound intermediate and the method for preparation formula (I) compound.These compounds can use the raw material, reagent and the conventional synthesis technique that obtain easily according to following reaction process preparation (wherein all variable all is defined as the front, and other has except the indication).In these reactions, also might utilize some to change, they itself are that those of ordinary skills are known, but do not mention in detail.

Abbreviation

The abbreviation that is used among flow process and the embodiment is as follows:

D=sky

G=gram

H=hour

Hz=hertz

KD=kilodalton

L=liter

M=volumetric molar concentration

Mbar=millibar

Mg=milligram

Min=minute

Ml=milliliter

MM=millimolar concentration

Mmol=mmole

Mol=mole

N=just

Ppm=1,000,000/umber

Psi=pound per square inch

APCI=atmospheric pressure chemical ionization

ESI=electrospray ionization

I.v.=intravenously

M/z=mass-charge ratio

Mp=fusing point

MS=mass spectrum

NMR=NMR (Nuclear Magnetic Resonance) spectrum

P.o.=per os

Rf=relative TLC movability

Rt=room temperature

S.c.=subcutaneous

TLC=thin-layer chromatography

Tr=retention time

BOP=(1-benzotriazole oxygen base) three (dimethylamino) phosphorus _ hexafluorophosphate

DCM=methylene dichloride

DIEA=diisopropylethylamine

DMF=N, dinethylformamide

DMPU=1,3-dimethyl allene urea

DMSO=dimethyl sulfoxide (DMSO)

EDC=1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide hydrochloride

Ether=diethyl ether

EtOAc=ethyl acetate

HMPA=hexamethyl phosphoric triamide

HOBt=I-hydroxybenzotriazole

LAH=lithium aluminium hydride

LDA=diisopropylamide lithium

MeOH=methyl alcohol

NMM=N-methylmorpholine, the 4-methylmorpholine

TEA=triethylamine

TFA=trifluoroacetic acid

THF=tetrahydrofuran (THF)

THP=tetrahydropyrans

TTF=fluoro-N, N, N '-tetramethyl-carbonamidine _ hexafluorophosphate (Fluoro-N, N, N '-tetramethyl formamidinium hexafluorophosphate)

Reaction process

Unless indication is arranged in addition, the variable in the flow process is defined suc as formula (I).

Flow process 1 is described the preparation of formula (74) compound.

A ²Be heteroaryl, annelated heterocycles base heteroaryl or fused rings alkyl heteroaryl.

R ¹⁰⁰And R ¹⁰¹Be such substituting group independently of one another, such as but not limited to H, alkyl, thiazolinyl, alkynyl ,-alkylidene group-aryl, alkylidene group-cyclic hydrocarbon radical etc.

K is halogen or 1-imidazolyl.

Can in a kind of solvent (for example DCM or DCE), amine (71) be handled with carbonyl dimidazoles, 4-chloroformate nitrophenyl ester, phosgene or phosgene derivative (for example two phosgene or triphosgene).In this reaction, can use DMAP as catalyzer.Reaction can be carried out under 0 ℃ to 100 ℃ temperature.Reaction mixture can be handled with compound (73) then, all constant temperature obtains urea (75) under 25 ℃ to 100 ℃ temperature.Also be understandable that, can under simulated condition, (73) be handled with reagent (72), succeeded by handling with amine (71), obtain (74).

Flow process 2 is described the preparation of formula (79) compound.

L ¹¹Has L in the formula (I) ¹Implication, if its condition is L ¹¹Be-D-alkylidene group-E-,-D-alkenylene-E-,-D-alkynylene-E-,-the inferior cyclic hydrocarbon radical-E-of D-or-the inferior heterocyclic radical-E-of D-, then D be selected from-O-or-S-, and L ¹¹Be not-S (O)-,-S (O) ₂-,-C (O)-or-C (=N-OR ¹²)-.

Lg ¹Be leavings group, for example F, Cl, Br or I.

R ¹⁰¹Be such substituting group, such as but not limited to H, alkyl, thiazolinyl, alkynyl ,-alkylidene group-aryl, alkylidene group-cyclic hydrocarbon radical etc.

Can be in the presence of alkali (for example NaH or potassium tert.-butoxide), in solvent (for example THF, DMF or NMP), under 0 ℃ to 100 ℃ temperature, the aryl that nitro is replaced or heteroaryl ring compound, for example (75) handle with (76), obtain (77).Can in ethanol or other alcohol solvents, under 25 ℃ to 100 ℃ temperature, in the presence of moisture HCl, gained adducts (77) be handled with tin chloride (II), obtain amine (78).If necessary, amine (78) can be used alkylogen R ¹⁰¹-Lg ²(Lg wherein ²Be leavings group, for example Br, I or right-tosylate) and alkali (for example DBU or sodium hydride) handle, obtain (79).Select as an alternative, can reductive agent for example sodium cyanoborohydride or sodium triacetoxy borohydride in the presence of, (78) are used reagent R ¹⁰²-C (O)-R ¹⁰³Handle, wherein R ¹⁰²And R ¹⁰³Be such substituting group independently of one another, such as but not limited to H, alkyl, thiazolinyl, alkynyl ,-alkylidene group-aryl, alkylidene group-cyclic hydrocarbon radical etc., obtain (79), wherein R ¹⁰¹Be appreciated that R ¹⁰²-C (H) (R ¹⁰³)-.

Select as an alternative, can dewatering agent for example EDC in the presence of, (78) are used reagent R ¹⁰²C (O)-OH handles, and obtains midbody acid amide, for example among the THF, under 0 ℃ to 80 ℃ temperature, with for example DIBAL or LAH reduction of reagent, obtains (71), wherein R at solvent again ¹⁰²Be appreciated that-CH ₂-R ¹⁰²Select as an alternative, wherein R ¹⁰¹Be-CH ₃(79) can prepare like this, namely alkali for example TEA or buck in the presence of, (78) are used reagent R ¹⁰²-O-CO-Cl or R ¹⁰²O-CO-O-CO-O-R ¹⁰²Handle, obtain intermediate, can obtain (79) as above-mentioned with DIBAL or LAH reduction again.According to the chemistry in the flow process (1), can adopt compound (79) according to the mode identical with compound (73).

Flow process 3 is described the preparation of formula (71) compound.

A ²Be heteroaryl, the annelated heterocycles base heteroaryl of (not) replacement or the fused rings alkyl heteroaryl that (not) replaces that (not) replaces.

R ¹⁰⁰Be such substituting group, the alkyl that replaces such as but not limited to H, (not), the thiazolinyl that (not) replaces, alkynyl, (not) that (not) replaces replace-and alkylidene group-aryl, (not) replace-alkylidene group-cyclic hydrocarbon radical etc.

If necessary, amine (80) can be used alkylogen R ¹⁰⁰-Lg ²(Lg wherein ²Be leavings group, for example Br, I or right-tosylate) and alkali (for example DBU or sodium hydride) handle, obtain (71).Select as an alternative, can reductive agent for example sodium cyanoborohydride or sodium triacetoxy borohydride in the presence of, (80) are used reagent R ¹⁰²-C (O)-R ¹⁰³Handle, wherein R ¹⁰²And R ¹⁰³Be such substituting group independently of one another, such as but not limited to H, alkyl, thiazolinyl, alkynyl ,-alkylidene group-aryl ,-alkylidene group-cyclic hydrocarbon radical etc., obtain (71), wherein R ¹⁰⁰Be appreciated that R ¹⁰²-C (H) (R ¹⁰³)-.

Select as an alternative, can dewatering agent for example EDC in the presence of, will (78) usefulness reagent (R for example ¹⁰²C (O)-Cl) and alkali (for example TEA or R ¹⁰²C (O)-OH) handles, and obtains midbody acid amide, for example among the THF, under 0 ℃ to 80 ℃ temperature, with for example DIBAL or LAH reduction of reagent, obtains (71), wherein R at solvent again ¹⁰⁰Be appreciated that-CH ₂-R ¹⁰²Select as an alternative, wherein R ¹⁰⁰Be-CH ₃(71) can prepare like this, namely alkali for example TEA or buck in the presence of, (78) are used reagent R ¹⁰²-O-C (O)-Cl or R ¹⁰²O-C (O)-O-C (O)-O-R ¹⁰²Handle, obtain intermediate, can obtain (71) as above with DIBAL or LAH reduction again.

Flow process 4 is described the synthetic of formula (81) compound.

A ²Be heteroaryl, the annelated heterocycles base heteroaryl of (not) replacement or the fused rings alkyl heteroaryl that (not) replaces that (not) replaces.

R ¹⁰⁰With ¹⁰¹Be such substituting group independently of one another, the alkyl that replaces such as but not limited to H, (not), the thiazolinyl that (not) replaces, alkynyl, (not) that (not) replaces replace-and alkylidene group-aryl, (not) replace-alkylidene group-cyclic hydrocarbon radical etc.

Can alkali for example DIEA in the presence of,, under-60 ℃ to 25 ℃ temperature, amine (73) is handled with the chloroformyl ester of reagent isocyanic acid for example in THF, DCE or the two _ alkane at solvent.Can under 0 ℃ to 80 ℃ temperature, the intermediate that generates be handled with (71), obtain (81).

Flow process 5 is described the preparation of formula (87) intermediate.

L ¹¹For example be the group of (not) alkylidene group of replacing and so on or direct key in this case.

R ¹⁰⁴Be such substituting group, the alkyl that replaces such as but not limited to (not), the aryl that (not) replaces, thiazolinyl that (not) replaces, alkynyl, (not) that (not) replaces replace-and alkylidene group-aryl, (not) replace-alkylidene group-cyclic hydrocarbon radical etc.

Can alkali for example TEA or buck in the presence of, anthranilic acid (82) is used acyl chlorides R ¹⁰⁴-CO-Cl handles, and obtains amide intermediate, again can be at solvent for example among the DCE, and under 0 ℃ to 80 ℃ temperature, with dewatering agent POCl for example ₃Or SOCl ₂Handle, obtain (83).Reagent (84) can be from active metallization agent (for example lithium or magnesium metal) and G ¹-L ¹¹-Br or G ¹-L ¹¹-I preparation.For example, if G ¹Be aryl, L ¹¹Be direct key, then can be at solvent for example in the ether, under-78 ℃ to 0 ℃ temperature, with G ¹-L ¹¹-Br handles with n-Butyl Lithium, obtains wherein M ¹Be the reagent (84) of Li.Can for example among the THF, under-78 ℃ to 50 ℃ temperature, (84) be handled with (83) at solvent, obtain (85).Can for example in the ethanol, under 25 ℃ to 100 ℃ temperature, acid amides (85) be handled with buck at solvent, obtain (86).

It is synthetic that flow process 6 is described substituting of formula (88) compound.

L ¹²Be such group in this case, such as but not limited to the alkylidene group of (not) replacement, inferior cyclic hydrocarbon radical or the direct key that (not) replaces.

Can in the presence of boron trichloride, under-40 ℃ to 25 ℃ temperature, (87) be handled with acyl chlorides or other carboxylic acid halides, succeeded by handling with gallium chloride (III) and chlorobenzene and under 50 ℃ to 150 ℃ temperature, heating, obtain (88).

Flow process 7 is described the synthetic of formula (91), (92), (93), (94) and (95) intermediate.

L ¹³Be such group, for example oxygen perhaps can be as L ¹²And L ¹¹The extensive group of definition.R ¹⁰⁶, R ¹⁰⁷And R ¹⁰⁸Be such group, the alkyl, (not) that replace such as but not limited to (not) replace-alkylidene group-aryl or H.

Can be in tetracol phenixin, nitrotoluene (89) with reagent N-bromine succinimide bromination for example, is obtained bromide intermediate (90).(89) methyl in also can with A ¹Hydrogen on the adjacent carbon constitutes more complicated alkyl.Bromide (90) can be handled with methane-sulfinic acid sodium and be obtained intermediate (91), handle obtaining intermediate (92) with secondary amine or primary amine.Select compound R as an alternative ¹⁰⁶R ¹⁰⁷R among the NH ¹⁰⁶And R ¹⁰⁷Group can constitute heteroaryl or heterocyclic radical together, alkali for example potassium tert.-butoxide in the presence of, (90) with a kind of like this compound treatment, are obtained (92), wherein R ¹⁰⁶And R ¹⁰⁷Group constitutes heteroaryl or heterocyclic radical together.Select as an alternative, (90) can be handled with thiol-acetic acid sodium, succeeded by using the buck hydrolysis, obtain mercaptan (91).Can prepare all cpds from (91).For example, alkali for example sodium hydride in the presence of, with (91) with alkylating agent for example alkyl bromide handle, obtain (93), wherein L ¹⁴Be S, R ¹⁰⁵It is alkyl.With this compound with reagent for example between-oxidation of chlorine peroxybenzoic acid, can obtain wherein L ¹⁴Be-SO ₂-compound.Can alkali for example pyridine in the presence of, will be wherein R ¹⁰⁶The compound (92) that is H is used compound R ¹⁰⁸SO ₂Cl handles, and generates (95).Select as an alternative, can peptide coupling agent for example dicyclohexylcarbodiimide in the presence of, R wherein ¹⁰⁶(92) that are H use carboxylic acid R ¹⁰⁸COOH handles, and generates (94).

Flow process 8 is described the synthetic of formula (97) compound.

L ¹⁶Be oxygen.G ¹And L ¹⁶Preferably do not contain ketone, aldehyde, primary amine or secondary amine group in this case.

R ¹⁰⁹, R ¹⁰⁰And R ¹¹¹Be such group, alkylidene group-aryl that the alkyl that replaces such as but not limited to (not), H or (not) replace.R ¹⁰⁰And R ¹¹¹Can constitute heterocycle alternatively together.

Can be at solvent for example 1, in the 2-ethylene dichloride, be with or without acetic acid in the presence of, with formula (91) urea amine R ¹⁰⁰NHR ¹¹¹And reagent (for example sodium triacetoxy borohydride) reductive amination, obtain formula (92) compound.

Flow process 9 is described the synthetic of formula (100) and (101) compound.

L ¹⁷Be carbonyl or alkylsulfonyl.

Nitrophenyl urea (98) can be reduced to formula (99) anils.Intermediate (99) is handled with acyl chlorides or SULPHURYL CHLORIDE, can be obtained formula (100) compound.In the presence of sodium triacetoxy borohydride, intermediate (99) is used the aldehydes or ketones alkylation, obtain (101).Select as an alternative, (99) can be handled with dialkyl group halogen and alkali (for example DIEA), obtain (101), wherein R ¹¹³And R ¹¹⁴The nitrogen that is connected with them constitutes ring.

L ¹⁹Be such group in this case, (not) alkylidene group of replacing for example.R ¹¹⁵And R ¹¹⁶Be such group independently, for example (not) alkyl of replacing, alkylidene group-aryl or the H that (not) replaces.Select R as an alternative ¹¹⁵And R ¹¹⁶Can constitute heterocycle together.

Can coupling agent for example dicyclohexylcarbodiimide in the presence of, for example in THF or the methylene dichloride, make acid (102) and amine R at solvent ¹¹⁵NHR ¹¹⁶Coupling obtains (103).

A ³Be such group, the fused rings alkyl inferior heteroaryl that replaces of (not) inferior heteroaryl of replacing, annelated heterocycles base inferior heteroaryl that (not) replaces or (not) for example.

R ¹¹⁷Be such group, the heteroaryl that replaces of (not) alkyl of replacing, alkylidene group-aryl that (not) replaces, aryl that (not) replaces or (not) for example.

Can alkali for example DIEA in the presence of, under 50 ℃ to 150 ℃ temperature, compound (104) is handled with thiol reagent, obtain thioether (105).Can be at solvent for example in the methylene dichloride, with (105) with oxygenant for example between-oxidation of chlorine peroxybenzoic acid, obtain sulfone (106).If only adopt the oxygenant of monovalent, then can obtain sulfoxide.If adopt 2 equivalents or more oxygenant, then obtain sulfone.

Flow process 12 is described the synthetic of formula (109) compound.

A ³Be such group, the fused rings alkyl inferior heteroaryl that replaces of (not) inferior heteroaryl of replacing, annelated heterocycles base inferior heteroaryl that (not) replaces or (not) for example.

L ²⁰Be such group in this case, (not) alkylidene group of replacing for example.R ¹¹⁷Be such group, the heteroaryl that replaces of (not) alkyl of replacing, alkylidene group-aryl that (not) replaces, aryl that (not) replaces or (not) for example.Lg ²Be leavings group, for example muriate, methanesulfonates or right-tosylate.

Lg wherein ²Be the compound (107) of methanesulfonates can be like this from Lg wherein ²The precursor that is hydroxyl is synthetic, namely handles with methylsulfonyl chloride in the presence of pyridine.Then can alkali for example DIEA, potassium tert.-butoxide or sodium hydride in the presence of, (107) are handled with thiol reagent, obtain substitution product (108).Can as described in flow process 11, thioether product (108) be oxidized to sulfoxide or sulfone (109).

Flow process 13 is described the synthetic of formula (111) compound.

L ²¹Be such group, for example alkylidene group in this case.R ¹¹⁵And R ¹¹⁶Can have aforementioned implication, perhaps can be such group independently, for example the heteroaryl of the aryl of the alkylidene group-aryl of the alkyl of (not) replacement, (not) replacement, (not) replacement, H or (not) replacement.A ³Be such group, the fused rings alkyl inferior heteroaryl that replaces of (not) inferior heteroaryl of replacing, annelated heterocycles base inferior heteroaryl that (not) replaces or (not) for example.

Can coupling agent for example dicyclohexylcarbodiimide in the presence of, make acid (110) and amine R ¹¹⁵NHR ¹¹⁶Coupling obtains (111).

Flow process 14 is described the synthetic of formula (113) intermediate.

R ¹¹⁸And R ¹¹⁹Can be such group independently, the heteroaryl that replaces of (not) alkyl of replacing, alkylidene group-aryl that (not) replaces, aryl that (not) replaces, H or (not) for example.

Can be with or without irenine for example salt of wormwood or triethylamine in the presence of, for example in the ethanol, under 25 ℃ to 120 ℃ temperature, make thiocarbamide and brominated carbonyl compound (112) condensation at solvent, obtain (113).Bromo compound (112) can obtain by several different methods known in the art.For example, in THF with tetramethyleneimine _ tribromide hydrogen or in THF, in the presence of irenine (for example salt of wormwood), carry out the bromination of ketone with N-bromine succinimide, obtain (112).

Flow process 15 is described the synthetic of formula (117) intermediate.

Flow process 15

Flow process 15 shows the route of synthesis of (117) type diamide, wherein A ¹, L ¹, R ²⁰, R ¹, G ¹, G ²Be defined suc as formula (I).Use EDC/HOB t, can make amine (114) and activation oxalic acid or malonic ester coupling, obtain acid amides (115).Carry out with lithium hydroxide B tertiary butyl ester go the protection, obtain carboxylic acid (116), can use standard amide coupling reagent (for example PyBOP) coupling again, obtain (115) type diamide.

During the preparation process of embodiment compound, the intermediate in the above-mentioned flow process may be by amino, hydroxyl or carboxyl substituted, and they may need protection and go protection.

" amido protecting " expression generally is used for sealing or protection amino functionality and makes the amino substituting group of other functional group reactionses on the compound.The example of this class amino-blocking group comprises formyl radical, trityl, phthalimido, tribromo-acetyl base, chloracetyl, acetyl bromide and iodoacetyl; Urethane type protecting groups group, carbobenzoxy-(Cbz) for example, 4-phenyl carbobenzoxy-(Cbz), 2-methyl carbobenzoxy-(Cbz), 4-methoxyl group benzyloxy carbonyl, 4-fluorine carbobenzoxy-(Cbz), 4-benzyloxycarbonylchloride base, 3-benzyloxycarbonylchloride base, 2-benzyloxycarbonylchloride base, 2,4-dichloro carbobenzoxy-(Cbz), the 4-bromo-benzyloxycarbonyl, the 3-bromo-benzyloxycarbonyl, 4-nitro carbobenzoxy-(Cbz), 4-cyano benzyloxy-carbonyl, 2-(4-xenyl) isopropyl oxygen carbonyl, 1,1-phenylbenzene second-1-base oxygen carbonyl, 1,1-diphenylprop-1-base oxygen carbonyl, 2-phenyl third-2-base oxygen carbonyl, 2-(right-toluyl) third-2-base oxygen carbonyl, encircle penta oxygen carbonyl, 1-methyl ring penta oxygen carbonyl, hexamethylene oxygen carbonyl, 1-methyl cyclohexane oxygen carbonyl, 2-methyl cyclohexane oxygen carbonyl, 2-(4-toluyl alkylsulfonyl) ethoxycarbonyl, 2-(methylsulfonyl) ethoxycarbonyl, 2-(triphen phosphino-) ethoxycarbonyl, 9-fluorenylmethyloxycarbonyl (" FMOC "), tertbutyloxycarbonyl (" BOC "), 2-(trimethylsilyl) ethoxycarbonyl, allyloxycarbonyl, 1-(trimethylsilyl methyl) third-1-alkenyloxycarbonyl, the 5-benzisoxalyl methoxycarbonyl, 4-acetoxyl group carbobenzoxy-(Cbz), 2,2,2-trichloro-ethoxycarbonyl, 2-ethynyl-2-third oxygen carbonyl, the cyclopropyl methoxycarbonyl, 4-(oxygen base in the last of the ten Heavenly stems) carbobenzoxy-(Cbz), iso-borneol oxygen carbonyl, 1-piperidines oxygen carbonyl etc.; Amido protecting groups such as benzoyl methylsulfonyl, 2-(nitro) benzenesulfinyl, diphenyl phosphine oxide base.The kind of the amido protecting group that adopts is not crucial, as long as the amino of derivatize is stable to other locational reaction conditionss of formula (I) compound subsequently, and can be removed at required point, and saboteur's rest part not.Preferred amido protecting group is allyloxycarbonyl, tertbutyloxycarbonyl, 9-fluorenylmethyloxycarbonyl and trityl.Similar amino-blocking group of using in cynnematin, penicillin and the peptide field is also in the scope that above-mentioned term is contained.By the further example of the represented group of above-mentioned term referring to J.W.Barton, " Protective Groups InOrganic Chemistry ", J.G.W.McOmie, Ed., Plenum Press, NewYork, N.Y., 1973 and T.W.Greene, " Protective Groups in OrganicSynthesis ", John Wiley and Sons, New York, N.Y., 1981.Relevant term " protected amino " is defined as the amino that is replaced by above-mentioned amino-blocking group.

" hydroxyl protection " expression generally is used for sealing or protection carbinol-functional degree and makes the alcohol groups substituting group of other functional group reactionses on the compound.The example of this class alcohol-blocking group comprises 2-THP trtrahydropyranyl, 2-ethoxyethyl group, trityl, tribromo-acetyl base, urethane type blocking groups (for example carbobenzoxy-(Cbz)) and trialkylsilkl, and the example has trimethylsilyl, t-butyldimethylsilyl, phenyl dimetylsilyl, triisopropyl silyl and thexyl dimethylsilyl.The selection of the alcohol-blocking group that adopts is not crucial, as long as the alcohol groups of deriving is stable to other locational reaction conditionss of various compound subsequently, and can be removed at required point, and saboteur's rest part does not get final product.By the further example of the represented group of above-mentioned term referring to J.W.Barton, " Protective Groups In Organic Chemistry ", J.G.W.McOmie, Ed., Plenum Press, New York, N.Y., 1973 and T.W.Greene, " ProtectiveGroups in Organic Synthesis ", John Wiley and Sons, New York, N.Y., 1981.Relevant term " protected hydroxyl " or " protected alcohol " are defined as the hydroxyl that is replaced by above-mentioned hydroxyl-blocking group.

" carboxy protective " expression generally is used for sealing or protection-OH functionality and makes the carboxyl substituent of other functional group reactionses on the compound.The example of this class alcohol-blocking group comprises 2-THP trtrahydropyranyl, 2-ethoxyethyl group, trityl, allyl group, trimethylsilyl ethoxyl methyl, 2; 2; 2-three chloroethyls, benzyl and trialkylsilkl, the example have trimethylsilyl, t-butyldimethylsilyl, phenyl dimetylsilyl, triisopropyl silyl and thexyl dimethylsilyl.The selection of the carboxyl-blocking group that adopts is not crucial, as long as the alcohol groups of deriving is stable to other locational reaction conditionss of various compound subsequently, and can be removed at required point, and saboteur's rest part does not get final product.By the further example of the represented group of above-mentioned term referring to J.W.Barton, " Protective Groups In Organic Chemistry ", J.G.W.McOmie, Ed., Plenum Press, New York, N.Y., 1973 and T.W.Greene, " Protective Groups in Organic Synthesis ", John Wiley and Sons, New York, N.Y., 1981.Relevant term " protected carboxyl " is defined as the carboxyl that is replaced by above-mentioned carboxyl-blocking group.

Embodiment

Common processes A:1-aryloxy-2-oil of mirbane, 1-arylthio-2-oil of mirbane and 2-virtue The preparation of oxygen base-3-nitropyridine

At room temperature, (0.62g, dry DMF 5.5mmol) (10mL) solution adds phenol, aryl mercaptan or 2-mercaptopyridine (5.5mmol), and mixture is stirred 30min to potassium tert.-butoxide.Add 1-fluoro-2-nitrobenzene derivative or 2-bromo-3-nitropyridine (5.0mmol), content is heated 12h down at 80 ℃.Content is poured in the water, used ethyl acetate extraction.With organic layer washing (rare NaOH, water, salt solution), dry (Na ₂SO ₄), concentrate.Generally speaking, required product is＞90% pure, be directly used in further operation.

Common processes B:2-Aryloxyaniline, 2-arylthio aniline and 3-amino-2-virtue oxygen The preparation of yl pyridines

To replace from the thick 2-of technology A-1-oil of mirbane is dissolved in ethanol (10mL).(3.8g is 20mmol) with dense HCl (0.2mL) to add anhydrous stannic chloride (II) to this solution.The gained mixture is heated 10h down at 80 ℃, and cooling concentrates.With resistates water (100mL) dilution, be neutralized to pH8-9, add ethyl acetate (40mL) to this suspension, stir 5min, filter by Celite.Separate each layer, water layer ethyl acetate extraction (2x10mL).Merge organic layer, use the salt water washing, dry (Na ₂SO ₄), under reduced pressure concentrate, obtain required aniline, yield 60-70%.Generally speaking, required aniline is＞85% pure (LC-MS), is directly used in further operation.

The preparation of common processes C:2-Aryloxyaniline and 2-arylthio aniline

In the 100ml round-bottomed flask, with thick 2-replace-1-oil of mirbane (5mmol) is dissolved in methyl alcohol (10mL).Add 10% palladium on carbon (300mg) to this solution, with the flask emptying.Fill hydrogen by air bag to flask, contents stirred is spent the night.Mixture is filtered by Celite, concentrate, obtain required aniline (LC-MS purity＞90%).

Common processes D: the preparation of urea

With 1, and 1 '-carbonyl dimidazoles (98mg, 0.6mmol), the amino assorted aromatic hydrocarbons (0.6mmol) of 2-and the mixture of 4-(N, N-dimethylamino) pyridine (5mg) in ethylene dichloride (5mL) be at 80 ℃ of heating 2h down.Reaction mixture is cooled to room temperature, adds ethylene dichloride (2mL) solution of the aniline (0.5mmol) that replaces.The gained suspension is heated 10h down at 80 ℃, concentrate.Resistates is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 10-30% ethyl acetate then ₂Cl ₂), obtain required urea, yield 60-80%.

Common processes E: the preparation of urea

Isocyanic ester (0.5mmol) and the amino assorted mixture of aromatic hydrocarbons (0.5mmol) in ethylene dichloride (4mL) of 2-are heated 12h down at 80 ℃.Reaction mixture is under reduced pressure concentrated.Resistates is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 10-30% ethyl acetate then ₂Cl ₂), obtain required urea, yield 60-80%.

The preparation of common processes F:2-aryloxy-1-oil of mirbane

Under-10 ℃, (0.62g, anhydrous THF (20mL) solution 5.5mmol) adds phenol (5.5mmol), and mixture is stirred 30min to potassium tert.-butoxide.Add fluoro-1-nitrobenzene derivative (5.0mmol) down at-10 ℃, at room temperature stir 12h.Content is poured in the water (25mL), with ethyl acetate extraction (3x20mL).With organic layer washing (rare NaOH, water, salt solution), dry (Na ₂SO ₄), concentrate, obtain required product, LC-MS purity＞90% is directly used in next step.

The preparation of common processes G:1-alkoxyl group-2-oil of mirbane

At room temperature, (60%, 0.20g, anhydrous THF (10mL) suspension 5.0mmol) drips alcohol (5.0mmol), and mixture is stirred 30min to NaH.Add 1-fluoro-2-oil of mirbane (5.0mmol), content is heated 12h down at 60 ℃.Content is poured in the water, used ethyl acetate extraction.With organic layer washing (rare NaOH, water, salt solution), dry (sodium sulfate) concentrates.Generally speaking, required product is＞90% pure, be directly used in further operation.

Common processes H: contain the general preparation of general formula (I) compound of urea part at centronucleus Technology

With the monovalent list-, two-or the three-aniline that replaces is dissolved in organic solvent, for example in ethyl acetate, toluene or the methylene dichloride, adds hydrochloride at organic solvent, for example the solution in ethyl acetate, toluene or the methylene dichloride.Mixture is concentrated in a vacuum, obtain the hydrochloride of aniline.Resistates is dissolved or suspended in aprotic organic solvent, for example in toluene or the methylene dichloride, adds excessive (for example 2 to 5 equivalents) two phosgene or another kind of phosgene Equivalent.Make mixture at room temperature or heating (to the solvent refluxing temperature) 5 to 20 hours.Reaction mixture is concentrated in a vacuum, and the intermediate resistates need not to be further purified and namely can be used for next step.

Thick intermediate isocyanic ester is dissolved in organic solvent, for example among ethyl acetate, toluene, methylene dichloride, two _ alkane, DMSO or the DMF, adds the monovalent heterocyclic amine.Make reaction mixture at room temperature or the heating until reacting.Temperature of reaction will depend on the reactivity of isocyanic ester and the nucleophilicity of amine, can monitor with HPLC or TLC.With the reaction mixture organic solvent, for example ethyl acetate, toluene or methylene dichloride dilution, the extraction of mixture water.With the product described standard technology in this area or purifying as described below.

Common processes H1: prepare acid amides from utilizing the prepared carboxylic acid of technology H

Aminothiazole-4-guanidine-acetic acid that aminothiazole-4-yl carboxylic acid that the N-that utilizes common processes H to prepare monovalent replaces or N-replace is dissolved in a kind of organic solvent, for example 1,2-propylene dichloride, dimethyl formamide, the perhaps mixture of two kinds of organic solvents, for example 1, in the mixture of 2-propylene dichloride and dimethyl formamide.Add monovalent PyBOP (benzotriazole-1-base-oxygen base-three-pyrrolidino-phosphorus _ hexafluorophosphate), made reaction mixture sat 20 minutes, succeeded by adding suitable amine and the DIPEA (diisopropylethylamine) of two equivalents, make the mixture standing over night.

Reaction mixture is diluted with ethyl acetate, utilizes the extraction of general washing process, for example wash with water twice, with 4N HCl washed twice, wash with water once, with 50% saturated sodium bicarbonate washed twice, wash with water three times.Evaporate organic solvent in a vacuum, obtain amorphous products.Product is through recrystallization in organic solvent (for example diethyl ether) or through HPLC (for example Waters Deltprep 4000) purifying.

Contain at the product that separates under the situation of carboxylicesters functionality, compound can be dissolved in 96% ethanol, add 2N NaOH, make ester group be hydrolyzed to corresponding acid.Make mixture leave standstill for some time (for example 2 hours), ethanol evaporation in a vacuum adds water then, regulates pH to acid with 2N HCl.With the mixture organic solvent, for example ethyl acetate extraction merges organic phase, and evaporation obtains amorphous products in a vacuum.

Common processes H2: the preparation of intermediate isocyanic ester

2-benzyl phenyl isocyanic ester

With the 2-benzylaniline (2.0g 11mmol) is dissolved in ethyl acetate (5mL), add hydrochloride ethyl acetate solution (3N, 5mL).Remove organic solvent behind the 2hr in a vacuum, obtain solid residue.Add toluene (50mL), (2.2g 33mmol), heats reaction mixture 16 hours down at 110 ℃ to add two phosgene then.Desolventizing and excessive two phosgene obtain residual oil in a vacuum, need not to be further purified namely to can be used for next step.

Utilize and prepare the following isocyanic ester of identical prepared with the benzyl phenyl isocyanic ester:

(5-chloro-2-isocyanic acid phenylester) phenyl ketone

2-(2-methylphenoxy) phenyl isocyanate

2-(4-methoxyl group phenoxy group)-5-(trifluoromethyl) phenyl isocyanate

2-(benzenesulfonyl) phenyl isocyanate

The preparation of common processes I:2-anilid

(110mL 0.11mol) is cooled to-20 ℃ with the dichloromethane solution of 1M boron trichloride.Methylene dichloride (100mL) solution that adds aniline (0.1mol) to this solution.Make mixture be warmed to room temperature, stir 3h.Mixture is cooled to again-20 ℃.Go through 5min and add alkyl nitrile (0.1mol), succeeded by 1M (anhydrous) GaCl ₃(100mL, dichloromethane solution 0.1mol).Add chlorobenzene (300mL) to this solution, mixture heating up is reached 24h to refluxing.After being cooled to room temperature, mixture is poured in the frozen water (1L), mixture is stirred 3h.Separate organic layer, water layer dichloromethane extraction (4x400mL).Merge organic layer, water (4x500mL), salt solution (2x500mL) washing are through anhydrous Na ₂SO ₄Dry.Then with water layer Na ₂CO ₃Alkalize to pH7.5 mixture dichloromethane extraction (2x400mL).With organic layer water (4x500mL), salt solution (2x500mL) washing, through anhydrous Na ₂SO ₄Dry.Merge two organic layers, concentrate in a vacuum.Crude mixture as eluent, obtains 2-amino-alkyl phenones, yield 10-50% with hexane-ethyl acetate (9: 1) through the column chromatography purifying.

Common processes J: from ester preparation acid

Ester (1mmol) is dissolved in 1: 1 mixture (5mL) of THF and methyl alcohol.To this solution add 2M LiOH solution (2mL, 4mmol).Mixture is stirred 1h, concentrate.With resistates water (10mL) dilution, water layer washs (2x10mL) with ether.Water layer is acidified to pH6.0 with HCl, the acid that precipitates ethyl acetate extraction (2x50mL).Organic layer is washed (2x20mL) with water dry (Na ₂SO ₄), concentrate in a vacuum, obtain required acid, yield almost is quantitative.

Common processes K: the preparation of acid amides

The mixture of acid (0.5mmol) and HBTU (0.5mmol) is dissolved in dry DMF (2mL).Add DIEA (0.6mmol) to this solution, stirred 2-3 minute.Add DMF (1mL) solution of alkylamine (0.5mmol), mixture is at room temperature stirred 30min.Mixture is poured in the water (20mL), with ethyl acetate extraction (2x20mL).With organic layer with saturated citric acid solution (5mL), NaHCO ₃(2x10mL), water (2x10mL), salt solution (2x10mL) wash dry (Na ₂SO ₄), concentrate in a vacuum, obtain required acid amides.Crude mixture is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 10-50% ethyl acetate then ₂Cl ₂), obtain acid amides, yield 50-75%.

Common processes L: the preparation of sulphonamide/acid amides

To anhydrous THF (20mL) the solution adding phenylbenzene azide phosphinylidyne (1.5mmol) of acid (1.0mmol) with DIEA (1.5mmol), being heated to refluxes reaches 8-12 hour.Concentrated reaction mixture in a vacuum obtains thick isocyanic ester then.(1.2M 20mL), reaches mixture heating up at 2 hours to refluxing to add rare HCl to this crude product.With reaction mixture Na ₂CO ₃Neutralization, water layer ethyl acetate extraction (3x30mL).With organic layer water (2x30mL), salt solution (1x30mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum, obtain required amine.Make this thick amine (1.0mmol) and aryl groups per alkyl group SULPHURYL CHLORIDE (1mmol) and Et ₃N (2mmol) reaction obtains required sulphonamide.Acid amides is as preparation as described in the technology K.Crude product obtains required sulphonamide, yield 20-30% through silica gel chromatography purifying [hexane: EtOAc/MeOH (70: 30: 0 to 5: 90: 5)].

Common processes M: the preparation of allophanamide or carbamate

The mixture of acid (1.0mmol) and DIEA (1.5mmol) is dissolved in anhydrous THF or CH ₃CN (30mL).Add phenylbenzene azide phosphinylidyne (1.5mmol) to reaction mixture then.Make reaction mixture refluxed 8-12 hour.Concentrated reaction mixture in a vacuum obtains thick isocyanic ester then.Add required amine or alcohol (2.0mmol) to this crude product, under rt, stir 2h.Concentrated reaction mixture in a vacuum then.Crude product mixture is passed through silica gel chromatography purifying (hexane: EtOAc 70: 30 to 10: 90) then, obtains required allophanamide or carbamate, yield 30-45%.

Common processes N: the preparation of alcohol

Under-10 ℃, anhydrous THF (100mL) solution to 2-amino-4-thiazolyl acetic acid ethyl ester or 2-amino-4-thiazolyl carboxylic acid ethyl ester (100mmol) adds lithium borohydride (200mmol, 2.0M THF solution), make mixture be warmed to envrionment temperature, stir 8-10h.Enriched mixture in a vacuum then.Add methyl alcohol (200mL) with the excessive lithium borohydride of quencher, filter by silica gel plug, obtain amino alcohol.

To dry DMF (50mL) the solution adding tert-butyldimethylsilyl chloride (500mmol) of this thick amino alcohol (100mmol) with imidazoles (500mmol), under rt, stir 6h.Then with reaction mixture water (5x100mL) and salt solution (2x100mL) washing, with ethyl acetate extraction (3x200mL), through Na ₂SO ₄Drying concentrates in a vacuum, obtains the amino alcohol of TBS-protection.

Amino alcohol (50mmol) according to the TBS-protection of common processes D carries out the generation of urea, obtains required urea.Should handle with TBAF (50mmol, 1.0M THF solution) by thick urea (25mmol) then, under rt, stir 4h.Reaction mixture is poured in the water, used ethyl acetate extraction.Merge organic extract liquid, washing (water), dry (Na ₂SO ₄), concentrate in a vacuum.Crude mixture obtains required alcohol, yield 70-80% through silica gel chromatography purifying [hexane: EtOAc (70: 30 to 10: 90)].

Common processes O: prepare amine by reductive amination

Ethylene dichloride or THF (5mL) solution to aldehyde (0.11mmol) add corresponding amine (0.11mmol), at room temperature stir 15min.Add sodium triacetoxy borohydride (0.16mmol) to this solution.At room temperature stir spend the night after, enriched mixture in a vacuum through column chromatography purifying (silicon-dioxide contains the DCM of 2-8%MeOH), obtains required product, yield 30-50%.

Common processes P: by Mitsunobu prepared in reaction aryl ethers

Under 0 ℃, to 1-[2-(pentamethylene carbonyl-4-methyl-phenyl]-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-urea (0.268mmol), phenol (0.536mmol) add diisopropyl azo-2-carboxylic acid (0.268mmol) with THF (2mL) solution of triphenyl phosphine (0.268mmol).Gained solution stirred under rt spend the night.Mixture is concentrated, through flash chromatography on silica gel purifying (10-50%EtOAc/ hexane), obtain required product, yield 28-40%.

Common processes Q:1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-alkylthio-2- Thiazolyl) urea is synthetic

1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-bromophenisic acid-2-thiazolyl) urea (1mmol), alkyl sulfhydryl (2mmol) are heated 3h with the mixture of DIEA (2mmol) in DMF (5mL) down at 80 ℃.Mixture is poured in the water (20mL), with ethyl acetate extraction (3x25mL).With organic layer water (2x30mL), salt solution (1x30mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum, obtain resistates, contain 1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-alkylthio-2-thiazolyl) urea and 1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(thiazol-2-yl) urea.Crude product is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 5-20% ethyl acetate then ₂Cl ₂), obtain required product, yield 25-35%.

Adopt identical technology to synthesize 1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-arylthio-2-thiazolyl) urea.Crude product is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 5-20% ethyl acetate then ₂Cl ₂With the CH that contains 2%MeOH ₂Cl ₂), obtain required product, yield 25-35%.

Common processes R: the oxidation of the thiazolyl urea that alkyl and arylthio replace

The thiazolyl urea (0.5mmol) of alkyl or arylthio replacement is dissolved in CH ₂Cl ₂(5mL), in ice bath, be cooled to 0 ℃.Add m-cpba (133mg, CH 0.75mmol) to this solution ₂Cl ₂(3mL) solution.Mixture is stirred 4h down at 0 ℃, use CH ₂Cl ₂(30mL) dilution.With the saturated NaHCO of organic layer ₃Solution (2x20mL), water (3x20mL), salt solution (1x20mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum.Crude mixture is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 5-20% ethyl acetate then ₂Cl ₂With the CH that contains 2%MeOH ₂Cl ₂), obtain required alkyl or aryl sulfone, yield 60-80%.

The preparation of common processes S:2-aminoaryl benzophenone

To the THF solution of 2-benzaminic acid (10mmol) add Benzoyl chloride (2.8g, 20mmol), succeeded by pyridine (1.58g, 20mmol).Mixture is at room temperature stirred 1h.Filter 2-phenyl-benzo [d] [1, the 3] _ piperazine-4-ketone that generates, resistates is washed with water, dry in vacuum drier.

Under 0 ℃, to the anhydrous CH of 2-phenyl-benzo [d] [1,3] _ piperazine-4-ketone (5mmol) ₂Cl ₂(20mL) solution adds the THF solution (5mL) of 1N aryl magnesium bromide.Mixture is at room temperature stirred 2h, pour in the water (30mL).With water layer ethyl acetate extraction (3x30mL), water (3x50mL), salt solution (1x50mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum, obtain N-(2-benzoyl-phenyl)-benzamide, yield 60-70%.

THF (10mL) solution to thick N-(2-benzoyl-phenyl)-benzamide (2mmol) adds 10N NaOH solution (5mL), and being heated to refluxes reaches 18h.Mixture is poured in the water (50mL), with ethyl acetate extraction (3x30mL).With organic layer water (3x50mL), salt solution (1x50mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum, obtain 2-aminoaryl benzophenone.Crude product obtains required product, yield 28-40% through column chromatography purifying (silicon-dioxide, hexane, 5-20% ethyl acetate then).

Common processes T: the preparation of acid amides/sulphonamide

DCM (5mL) solution to amine (0.5mmol) adds triethylamine (1mmol), and reaction mixture is cooled to 0 ℃.Drip acyl chlorides or SULPHURYL CHLORIDE (0.5mmol), stirring is spent the night.Concentrated reaction mixture in a vacuum, resistates obtains required acid amides or sulphonamide respectively through column chromatography purifying [silicon-dioxide, DCM: ethyl acetate (80: 20 to 20: 80)].

Common processes U: prepare glycolylurea from amino acid

(1.2g, 0.96mmol) solution adds trifluoroacetic acid (5mL, 20%DCM solution), then resin is washed three circulations with DMF, methyl alcohol and DCM to the Boc-Gly-Merrifield resin.Under-20 ℃ to the DCM solution (20mL) of this resin slowly add phosgene (10mL, 20% toluene solution, 2.0mmol) and triethylamine (0.56mL, 4.0mmol).Make reaction mixture be warmed to room temperature.With three DCM circulation flush away excess phosgene.DCM solution (20mL) to this resin adds 1-(4-aminomethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.9g, 2.5mmol) DCM (10mL) solution, reaction mixture is placed beaker, and reaction 4h obtains corresponding urea.Then resin is washed three circulations, dry 2h with DMF, methyl alcohol and DCM.Add triethylamine (10mL, 20%THF solution) to resin, reaction mixture is heated 16h.Filtering mixt, concentrated filtrate obtains glycolylurea in a vacuum, total recovery 60-75%.

Common processes V: the preparation of special thiazolamine analogue

To 1,3-Dichloro acetone, 1,3-dibromoacetone, 1-acetoxy-3-monochloroacetone, bromine mda (bromomalonaldehyde) or 1,4-dibromo fourth-2, methyl alcohol (100mL) solution of 3-diketone (100mmol) adds thiocarbamide, and (7.6g 100mmol), stirs 3h with mixture under rt.Concentrated reaction mixture obtains required product in a vacuum, and yield almost is quantitative.

According to common processes Z, (172mg 1.0mmol) reacts in THF (5mL) with aryl mercaptan (2mmol) and DIEA (2mmol) to make 4-chloromethyl-thiazol-2-yl amine.According to common processes D, make these intermediates and CDI and 2-amino-5-methyl-phenyl)-cyclopentyl-ketone (203mg, 1.0mmol) coupling.

Common processes W: the preparation of alkylamino oil of mirbane

With THF (25mL) solution 60 ℃ under the heating 12h of 1-fluoro-2-nitrobenzene derivative (5.0mmol) with amine (10mmol).Content is poured in the water, used ethyl acetate extraction.With organic layer washing (water, salt solution), dry (Na ₂SO ₄), concentrate.Resistates is dissolved in methyl alcohol (25mL), and C reduces according to common processes.Generally speaking, required product is＞90% pure, be directly used in further operation.

Common processes X: by Wittig prepared in reaction alkene

With aldehyde (0.10g, 0.28mmol) and (ethoxycarbonyl methylene radical)-triphenyl phosphine (0.12g, 0.34mmol) at room temperature, in benzene, stir and spend the night.Reaction mixture is concentrated under vacuum, through column chromatography purifying (silicon-dioxide, 15%EtOAc/ hexane), obtain product, yield 80%.

Common processes Y:1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-arylthio-2- Thiazolyl) urea is synthetic

With 1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-bromophenisic acid-2-thiazolyl) urea (1mmol), aryl mercaptan (2mmol) and t-BuOK (2mmol; 4 equivalent t-BuOK are used for the arylthio carboxylic acid) at the mixture of DMF (5mL) at 80 ℃ of heating 3h down.Mixture is poured in the water (20mL).The saturated NaHCO of urea that will contain the arylthio carboxylic acid ₃The solution neutralization.Water layer ethyl acetate extraction (3x25mL).With organic layer water (2x30mL), salt solution (1x30mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum, obtain resistates, contain 1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(5-arylthio-2-thiazolyl) urea and 1-(2-pentamethylene acyl group-4-methyl-phenyl)-3-(2-thiazolyl) urea.Crude product is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 5-20% ethyl acetate then ₂Cl ₂With the CH that contains 2%MeOH ₂Cl ₂), obtain required product, yield 25-35%.

Common processes Z:1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(arylthio first Base)-thiazol-2-yl]-urea and 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[virtue sulphur Base)-ethyl]-thiazol-2-yl }-urea synthetic

1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (1mmol), aryl mercaptan (2mmol) are heated 3h with the mixture of DIEA (2mmol) in THF (5mL) down at 80 ℃.Mixture is poured in the water (20mL), with ethyl acetate extraction (3x25mL).With organic layer water (2x30mL), salt solution (1x30mL) washing, dry (anhydrous Na ₂SO ₄), concentrate in a vacuum, obtain resistates, wherein contain 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(arylthio methyl)-thiazol-2-yl]-urea.Crude product is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 5-20% ethyl acetate then ₂Cl ₂With the CH that contains 2%MeOH ₂Cl ₂), obtain required product, yield 79-85%.

Similarly, make methylsulfonic acid 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl ester and aryl mercaptan and Et ₃1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[arylthio is carried out in N reaction)-ethyl]-thiazol-2-yl }-urea synthetic.Obtain required product, yield 60-80%.

Common processes AA: the preparation of urea

With 1, and 1 '-carbonyl dimidazoles (98mg, 0.6mmol), (thiazolamine-4-yl) acetic acid ethyl ester (0.6mmol) and the mixture of 4-(N, N-dimethylamino) pyridine (2mg) in methylene dichloride (5mL) at room temperature stir 2h.Methylene dichloride (1mL) solution that adds the anils (0.6mmol) that replaces continues at room temperature to stir 24h.Concentrated reaction mixture, resistates is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 10-30% ethyl acetate then ₂Cl ₂), obtain required urea.

HPLC-MS (method A)

Use following instrument:

·Hewlett?Packard?series?1100?G1312A?Bin?Pump

·Hewlett?Packrd?series?1100?Column?compartment

Hewlett Packard series 1100 G1315A DAD diode-array detectors

·Hewlett?Packard?series?1100?MSD

Sedere 75 light scattering detectors

Instrument is subjected to the control of HP Chemstation software.

The HPLC pump is connected two eluent storage storehouses, wherein contains:

A: the water that contains 0.01%TFA

B: the acetonitrile that contains 0.01%TFA

Analysis is performed such, and namely under 40 ℃, the sample (preferred 1 μ l) of proper volume is expelled on the pillar, uses the acetonitrile gradient wash-out.

Used HPLC condition, detector setting and mass spectrograph setting see table.

Pillar: Waters Xterra MS C-18X3mm id 5 μ m

Gradient: the 5%-100% acetonitrile is linear, flow velocity 1.5ml/min in 7.5min

Detect: 210nm (the similar output of DAD (diode-array detector))

ELS (the similar output of ELS)

MS ionization pattern: API-ES

Scanning 100-1000amu, step pitch 0.1amu

Shunting after the DAD, approximately 1ml/min to ELS and 0.5ml/min to MS.

Embodiment 1

N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea

N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea (0.59g, 94.9%) be from the 2-phenoxybenzamine (0.37g, 2.00mmol) and thiazolamine (0.20g is 2.00mmol) according to common processes D preparation.

LC-MS(m/z)：313(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.76 (d, J=13.8Hz, 1H), 6.98-7.04 (m, 4H), 7.11 (t, J=4.8Hz, 2H), 7.32 (t, J=8.0Hz, 2H) and 8.35 (dd, J=1.6,8.0Hz, 1H), 10.2 (br, 2H).

Embodiment 2

N-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl]-N '-(thiazol-2-yl) sulphonamide

Under-78 ℃, to sulfuryl chloride solution (2.0mL, 2.0mmol, the 1.0M solution in methylene dichloride) add right-nitrophenols (0.55g, dichloromethane solution 4.0mmol) and N, the N-diisopropylethylamine (0.71mL, 4.0mmol).Reaction mixture was stirred 1 hour down at-78 ℃, add 2-(2,3-dimethoxy phenoxy group)-5-fluoroaniline (0.52g, methylene dichloride 2.0mmol) (5mL) solution.Reaction mixture is stirred 10min, and the adding thiazolamine (0.2g, 2.0mmol).Make reaction mixture slowly be warmed to envrionment temperature.Enriched mixture under reduced pressure.Resistates is dissolved in ethyl acetate, washing (rare NaOH, water, salt solution), dry (Na ₂SO ₄), under reduced pressure concentrate.Crude product is handled with the Dowex-50 acidic resins in ethyl acetate-methyl alcohol (1: 1), to remove unreacted thiazolamine.Concentrated filtrate, resistates through silica gel chromatography (ethyl acetate: hexane, from 50: 50 to 90: 10 as elution system), obtain title compound (0.42g, 49%).

LC-MS(m/z)：427(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.12 (br, 2H), 3.71 (s, 3H), 3.86 (s, 3H), 6.56 (dd, J=7.6,1.6Hz, 1H), 6.66 (m, 1H), 6.77-6.87 (m, 3H), 6.99 (t, J=3.6Hz, 1H), 7.26 (d, J=4.8Hz, 1H) and 7.38 (dd, J=10.8,3.2Hz, 1H)

Embodiment 3

1-(2-Phenoxyphenyl)-5-(thiazol-2-yl) biuret

To the 2-phenoxybenzamine (0.46g, tetrahydrofuran (THF) 2.50mmol) (20mL) solution add diisopropylethylamine (0.89mL 5.00mmol), is cooled to solution-30 ℃, slowly add then N-(chloroformyl) isocyanic ester (0.3mL, 3.75mmol).Make mixture in 30min, be warmed to room temperature then.(0.375g 3.75mmol), at room temperature stirred reaction mixture 6 hours to add thiazolamine.Under reduced pressure concentrated reaction mixture obtains crude product, process silica gel chromatography purifying (hexane: ethyl acetate, from 80: 20 to 30: 70), obtain title compound (0.49g, 55%), be faint yellow solid.

LC-MS(m/z)：356(M+1).

¹H NMR (400MHz, acetone-d ₆): δ 6.92 (dd, J=1.6,7.6Hz, 1H), 7.06 (m, 5H), 7.40 (m, 3H), 8.32 (d, J=4.8Hz, 1H), 8.45 (d, J=5.6Hz, 1H), 9.02 (br, 1H), 9.78 (br, 1H) and 10.46 (br, 1H).

Embodiment 4

2-[([[(2-phenoxybenzamine base) alkylsulfonyl] amino] carbonyl) amino] thiazole

Under-78 ℃, to chloro sulfonyl isocyanate (0.22mL, tetrahydrofuran (THF) 2.5mmol) (25mL) solution add the 2-phenoxybenzamine (0.37g, 2.0mmol) and DIEA (0.89mL, 5.0mmol).Stir this solution, slowly be warmed to 0 ℃.(0.20g 2.0mmol), continues at room temperature to stir 3h to add thiazolamine to this reaction mixture.Reaction mixture is under reduced pressure concentrated, crude product through the column chromatography purifying (ethyl acetate: hexane, from 50: 50 to 90: 10 as elution system), obtain title compound (0.52g, 66%).

LC-MS(m/z)：392(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.85 (dd, J=8.8,1.6Hz, 1H), 6.88 (dd, J=1.6,8.8Hz, 1H), 7.00-7.16 (m, 5H), 7.29-7.39 (m, 4H), 10.33 (br, 1H), 10.88 (br, 2H).

Embodiment 5

N-(2-thiophenyl phenyl)-N '-(thiazol-2-yl) urea

N-(2-thiophenyl phenyl)-N '-(thiazol-2-yl) urea (116mg, 71%) be from 2-thiophenyl aniline (100mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：329(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 7.03 (d, J=3.6Hz, 1H), 7.10-7.18 (m, 4H), 7.25-7.31 (m, 3H), 7.48 (m, 1H), 7.59 (dd, J=3.6,1.6Hz, 1H), 8.44 (dd, J=8.4,1.2Hz, 1H), 9.00 (br, 1H), 10.44 (br, 1H).

Embodiment 6

N-(2-benzenesulfonyl phenyl)-N '-(thiazol-2-yl) urea

N-(2-benzenesulfonyl phenyl)-N '-(thiazol-2-yl) urea (98mg, 55%) be from the 2-benzenesulphonanilide (116mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 7.07 (d, J=3.6Hz, 1H), 7.33-7.37 (m, 1H), 7.40 (d, J=3.6Hz, 1H), 7.55-7.60 (m, 2H), 7.63-7.71 (m, 2H), 7.98-8.01 (m, 2H), 8.12 (d, J=8.0Hz, 1H), and 8.22-8.25 (m, 1H), 9.26 (br, 1H), 10.99 (br, 1H).

Embodiment 7

N-(2-benzyl phenyl)-N '-(thiazol-2-yl) urea

N-(2-benzyl phenyl)-N '-(thiazol-2-yl) urea (111mg, 72%) be from commercial available 2-benzylaniline (91mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：311(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 4.08 (s, 2H), 7.02 (d, J=3.2Hz, 1H), 7.06-7.14 (m, 2H), 7.14-7.19 (m, 4H), 7.23-7.29 (m, 4H), 7.96 (d, J=8.4Hz, 1H), 8.75 (br, 1H), 10.01 (br, 1H).

Embodiment 8

N-(2-benzoyl phenyl)-N '-(thiazol-2-yl) urea

N-(2-benzoyl phenyl)-N '-(thiazol-2-yl) urea (100mg, 63%) be from the 2-Uvinul A Plus (97mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：325(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 7.05 (s, 1H), 7.16 (s, 1H), 7.35 (d, J=3.6Hz, 1H), 7.54 (d, J=7.2Hz, 2H), 7.65 (s, 1H), 7.75 (s, 1H), 8.45 (s, 1H), 10.18 (br, 1H), 10.85 (br, 1H).

Embodiment 9

N-[2-(phenyl amino) phenyl]-N '-(thiazol-2-yl) urea

N-[2-(phenyl amino) phenyl]-N '-(thiazol-2-yl) urea (75mg, 49%) be from 2-(N-phenyl amino) aniline (92mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：312(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.75-6.79 (m, 3H), 6.86 (br, 1H), 7.01 (d, J=3.6Hz, 1H), 7.05-7.09 (m, 1H), 7.15-7.19 (m, 3H), 7.24-7.28 (m, 2H), 8.16 (d, J=8.0,1.2Hz, 1H), 8.65 (br, 1H), 10.15 (br, 1H).

Embodiment 10

N-[2-fluoro-6-(4-methoxyl group phenoxy group) benzyl]-N '-(thiazol-2-yl) urea

N-[2-fluoro-6-(4-methoxyl group phenoxy group) benzyl]-N '-(thiazol-2-yl) urea (0.61g, 81%) be from 2-fluoro-6-(4-methoxyl group phenoxy group) benzyl amine (0.494g, 2.00mmol) and thiazolamine (0.20g is 2.00mmol) according to common processes D preparation.

LC-MS(m/z)：327(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.06 (br, 1H), 3.78 (s, 3H), 4.67 (d, J=4.8Hz, 2H), 6.52 (d, J=8.4Hz, 1H), 6.85 (t, J=9.6Hz, 1H), 6.95 (m, 3H), 7.05 (m, 2H), 7.24 (m, 2H), 10.06 (br, 1H).

Embodiment 11

N-(2-benzyloxy phenyl)-N '-(thiazol-2-yl) urea

N-(2-benzyloxy phenyl)-N '-(thiazol-2-yl) urea (0.56g, 86%) be from the 2-benzyloxy-aniline (0.40g, 2.00mmol) and thiazolamine (0.20g is 2.00mmol) according to common processes D preparation.

LC-MS(m/z)：327(M+1).

¹H NMR (400MHz, CDCl ₃): δ 4.00 (br, 2H), 5.15 (s, 2H), 6.85 (dd, J=1.6,8.8Hz, 2H), 6.97 (dd, J=1.6,7.2Hz, 1H), 6.98 (dd, J=2.0,6.0Hz, 1H), 7.37 (m, 2H), 7.46 (t, J=7.2Hz, 1H), 7.52 (d, J=5.6Hz, 2H) and 7.56 (d, J=6.8Hz, 2H)

Embodiment 12

N-[2-(2,3,4-trimethoxy benzyloxy) phenyl]-N '-(thiazol-2-yl) urea

2-(2,3,4-trimethoxy benzyloxy)-1-oil of mirbane (0.46g, 72%) is that (0.35mL, 2.0mmol) (0.21mL 2.0mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from 2,3,4-trimethoxy benzyl alcohol.According to common processes B, it is reduced to 2-(2,3,4-trimethoxy benzyloxy) aniline (0.26g, 65%).N-[2-(2,3,4-trimethoxy benzyloxy) phenyl]-N '-(thiazol-2-yl) urea (240mg, 65%) be from 2-(2,3,4-trimethoxy benzyloxy) aniline (0.26g, 0.9mmol) and thiazolamine (140mg is 1.4mmol) according to common processes D preparation.

LC-MS(m/z)：417(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.72 (s, 3H), 3.73 (s, 3H), 3.81 (s, 3H), 3.88 (s, 2H), 6.73-7.36 (m, 7H), 8.15 (t, J=8.4Hz, 1H), 8.90 (br, 1H), 10.10 (br, 1H).

Embodiment 13

N-(2-ethoxyl phenenyl)-N '-(thiazol-2-yl) urea

N-(2-ethoxyl phenenyl)-N '-(thiazol-2-yl) urea (95mg, 72%) be from commercial available 2-phenetidine (68mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：265(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.29 (t, J=7.0Hz, 3H), 3.94-3.98 (q, J=7.0Hz, 2H), 6.74-6.88 (m, 4H), 7.27 (d, J=5.2Hz, 1H), 8.17 (dd, J=1.6,8.0Hz, 1H), 8.42 (br, 1H), 10.92 (br, 1H).

Embodiment 14

N-(2-Phenoxyphenyl)-N '-(pyridine-2-yl) urea

N-(2-Phenoxyphenyl)-N '-(pyridine-2-yl) urea (109mg, 72%) is that (106mg, 0.5mmol) (60mg 0.6mmol) prepares according to common processes E with the 2-aminopyridine from 2-Phenoxyphenyl isocyanic ester.

LC-MS(m/z)：307(M+1) ⁺.

¹H?NMR(400MHz，DMSO-d ₆)：δ6.88-6.91(m，1H)，6.96-7.08(m，4H)，7.15-7.19(m，2H)，7.32-7.36(m，2H)，7.65-7.69(m，1H)，7.88(d，J＝4.0Hz，1H)，8.36?d，J＝8.0Hz，1H)，9.84(s，1H)，11.5(br，1H).

Embodiment 15

N-(2-Phenoxyphenyl)-N '-[(4-methoxycarbonyl methyl) thiazol-2-yl] urea

N-(2-Phenoxyphenyl)-N '-[(4-methoxycarbonyl methyl) thiazol-2-yl] urea (130mg, 65%) be from 2-Phenoxyphenyl isocyanic ester (106mg, 0.5mmol) and methyl thiazolamine-4-acetic ester (104mg is 0.6mmol) according to common processes E preparation.

LC-MS(m/z)：401(M+1) ⁺.

¹H NMR (400 MHz, acetone-d ₆): δ 3.58 (s, 2H), 3.61 (s, 3H), 6.84-6.89 (m, 2H), 7.01-7.05 (m, 3H), 7.13-7.18 (m, 2H), 7.38-8.42 (m, 2H), 8.40 (d, J=8.0Hz, 1H), 8.91 (br, 1H), 10.12 (br, 1H).

Embodiment 16

N-methyl-N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea

With the 2-phenoxybenzamine (0.93g, 5.00mmol) and tert-Butyl dicarbonate (2.18g 10.0mmol) is dissolved in anhydrous two _ alkane (50mL), makes reaction mixture refluxed 3h then.Under reduced pressure enriched mixture quantitatively obtains 2-phenoxy group-N-(tertbutyloxycarbonyl) aniline (1.43g).Product obtains the affirmation of LC-MS, need not to be further purified to carry out next reaction.

Under-10 ℃, (1.43g, the anhydrous tetrahydro furan of 5.0mmol (50mL) solution adds lithium aluminium hydride (10mL, 10.0mmol, the 1.0M solution in tetrahydrofuran (THF)) to 2-phenoxy group-N-(tertbutyloxycarbonyl) aniline.Then reaction mixture is flow through night next time at 65 ℃.Slowly add MeOH (10mL) to reaction mixture and carry out quencher, under reduced pressure concentrate.Then reaction mixture is poured in the water (50mL), with ethyl acetate extraction (3x100mL).Merge organic extract liquid, with salt water washing (2x100mL), through Na ₂SO ₄Drying under reduced pressure concentrates, and obtains N-methyl-2-phenoxybenzamine (0.94g, 94.0%), is light yellow oil.Product obtains the affirmation of LC-MS, need not to be further purified to carry out next reaction.

To thiazolamine (0.20g, ethylene dichloride 2.00mmol) (20mL) solution add 1,1 '-carbonyl dimidazoles (0.40g, 2.5mmol) and N, the N-Dimethylamino pyridine (0.05g, 0.4mmol), then with solution at 80 ℃ of following backflow 1h.To solution add N-methyl-2-phenoxybenzamine (0.40g, 2.00mmol).Then reaction mixture is stirred down at 80 ℃ and spend the night.With LC-MS and TLC monitoring reaction, under reduced pressure concentrate then, obtain crude product, carry out subsequently the silica gel chromatography purifying (hexane: ethyl acetate, from 80: 20 to 50: 50 as elution system), obtain title product (0.48g, 73%), be orange solids.

LC-MS(m/z)：327(M+1) ⁺.

¹H NMR (400MHz, CDCl ₃): δ 3.30 (s, 3H), 6.84 (d, J=4.8Hz, 1H), 6.97 (m, 3H), 7.16 (m, 2H), 7.29 (m, 5H) and 7.74 (br, 1H).

Embodiment 17

N-sec.-propyl-N-(2-Phenoxyphenyl)-N '-(thiazol-2-yl) urea

To the 2-phenoxybenzamine (0.93g, ethylene dichloride 5.0mmol) (50mL) solution add anhydrous propanone (0.73mL, 10.0mmol) and acetic acid (0.1mL, 2.0mmol).Mixture is stirred 30min, and disposable adding sodium triacetoxy borohydride (3.18g, 15.0mmol).Reaction mixture stirred at ambient temperature spend the night.Slowly add MeOH (10mL) to reaction mixture and carry out quencher, under reduced pressure concentrate.Resistates is poured in the water (50mL), with ethyl acetate extraction (3x100mL).Merge organic extract liquid, with salt water washing (2x100mL), dry (Na ₂SO ₄), under reduced pressure concentrate, obtain N-sec.-propyl-2-phenoxybenzamine (1.05g, 91%), be colourless oil.

To thiazolamine (0.20g, ethylene dichloride 2.00mmol) (20mL) solution add 1,1 '-carbonyl dimidazoles (0.40g, 2.5mmol) and N, the N-Dimethylamino pyridine (0.05g, 0.4mmol), then with solution at 80 ℃ of following backflow 1h.(0.46g 2.0mmol), stirs reaction mixture down at 80 ℃ then and spends the night to add N-sec.-propyl-2-phenoxybenzamine.Under reduced pressure concentrated reaction mixture obtains crude product, through the silica gel chromatography purifying (hexane: ethyl acetate, from 80: 20 to 50: 50 as elution system), obtain title product (0.56g, 79%).

LC-MS(m/z)：355(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.22 (d, J=6.4Hz, 6H), 4.81 (m, 1H), 6.91 (m, 2H), 7.10-7.24 (m, 5H), 7.39 (m, 4H) and 9.00 (br, 1H).

Embodiment 18

N-[2-(4-methoxyl group phenoxy group) phenyl)-N '-(thiazol-2-yl) urea

2-(4-methoxyl group phenoxy group)-1-oil of mirbane (0.98g, 80%) is that (0.62g, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 4-methoxyphenol.According to common processes B, it is reduced to 2-(4-methoxyl group phenoxy group) aniline (0.32g, 60%, 2.5mmol scale).N-[2-(4-methoxyl group phenoxy group) phenyl)-N '-(thiazol-2-yl) urea (256mg, 75%) be from 2-(4-methoxyl group phenoxy group) aniline (215mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：343(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.80 (s, 3H), 6.80 (d, J=8.0Hz, 1H), 6.98-7.05 (m, 6H), 7.10 (m, 1H), 7.32 (d, J=3.6Hz, 1H), 8.40 (d, J=8.0Hz, 1H), 8.90 (br, 1H), 10.23 (br, 1H).

Embodiment 19

N-[2-(4-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(4-fluorophenoxy)-1-oil of mirbane (0.87g, 75%) is that (0.62g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 4-fluorophenol.According to common processes B, it is reduced to 2-(4-fluorophenoxy) aniline (0.51g, 68%).N-[2-(4-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (118mg, 72%) be from 2-(4-fluorophenoxy) aniline (102mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：331(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.89 (dd, J=8.4,1.2Hz, 1H), 7.01-7.11 (m, 4H), 7.14-7.29 (m, 3H), 7.31 (d, J=3.6Hz, 1H), 8.42 (dd, J=8.0,1.6Hz, 1H), 9.12 (br, 1H), 10.19 (br, 1H).

Embodiment 20

N-[2-(4-chlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(4-chlorophenoxy)-1-oil of mirbane (0.88g, 71%) is that (0.70g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 4-chlorophenol.According to common processes B, it is reduced to 2-(4-chlorophenoxy) aniline (0.50g, 65%).N-[2-(4-chlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (106mg, 62%) be from 2-(4-chlorophenoxy) aniline (109mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：347(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.98 (d, J=7.6Hz, 1H), 7.04-7.09 (m, 4H), 7.19-7.23 (m, 1H), 7.31 (d, J=3.6Hz, 1H), 7.39-7.43 (m, 2H), 8.44 (dd, J=8.4,1.6Hz, 1H), 8.90 (br, 1H), 10.13 (br, 1H).

Embodiment 21

N-[2-(4-cyano-benzene oxygen) phenyl]-N '-thiazolyl urea

2-(4-cyano-benzene oxygen)-1-oil of mirbane (0.82g, 69%) is that (0.66g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 4-cyanophenol.According to common processes B, it is reduced to 2-(4-cyano-benzene oxygen) aniline (0.47g, 65%).N-[2-(4-cyano-benzene oxygen) phenyl]-N '-thiazolyl urea (110mg, 65%) be from 2-(4-cyano-benzene oxygen) aniline (105mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：338(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.04 (d, J=8.0Hz, 1H), 7.13-7.18 (m, 4H), 7.28-7.33 (m, 2H), 7.78-7.81 (m, 2H), 8.47 (d, J=8.0Hz, 1H), 8.95 (br, 1H), 10.43 (br, 1H).

Embodiment 22

N-[2-(4-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(4-methoxycarbonyl phenoxy group)-1-oil of mirbane (0.79g, 58%) is that (0.84g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from methyl 4-hydroxybenzoate.According to common processes B, it is reduced to 2-(4-methoxycarbonyl phenoxy group) aniline (0.46g, 66%).N-[2-(4-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (100mg, 55%) be from 2-(4-methoxycarbonyl phenoxy group) aniline (122mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：371(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.85 (s, 3H), 7.03 (d, J=3.6Hz, 1H), 7.07-7.14 (m, 4H), 7.25-7.29 (m, 2H), 8.01-4.04 (m, 2H), 8.46 (dd, J=8.1,1.2Hz, 1H), 8.76 (br, 1H), 10.07 (br, 1H).

Embodiment 23

N-[2-(4-sec.-propyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(4-sec.-propyl phenoxy group)-1-oil of mirbane (0.95g, 75%) is that (0.68g, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 4-isopropyl-phenol.According to common processes B, it is reduced to 2-(4-sec.-propyl phenoxy group) aniline (0.34g, 60%, 2.5mmol scale).N-[2-(4-sec.-propyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (247mg, 70%) be from 2-(4-sec.-propyl phenoxy group) aniline (227mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：355(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.17 (d, J=7.2Hz, 3H), 1.22 (d, J=6.8Hz, 3H), 2.88 (m, 1H), 6.74 (d, J=6.6Hz, 1H), 6.88 (d, J=8.0Hz, 1H), 6.94-7.15 (m, 4H), 7.28 (m, 2H), 8.43 (d, J=8.2Hz, 1H), 10.15 (br, 2H).

Embodiment 24

N-[2-(3,4-, two fluorophenoxies) phenyl]-N '-(thiazol-2-yl) urea

2-(3,4-, two fluorophenoxies)-1-oil of mirbane (0.76g, 60%) is that (0.65g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 3,4-difluorophenol.According to common processes B, it is reduced to 2-(3,4-, two fluorophenoxies) aniline (0.33g, 60%, 2.5mmol scale).N-[2-(3,4-, two fluorophenoxies) phenyl]-N '-(thiazol-2-yl) urea (312mg, 60%) be from 2-(3,4-, two fluorophenoxies) aniline (330mg, 1.5mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：349(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.88 (m, 1H), 7.01 (d, J=8.0Hz, 1H), 7.04-7.12 (m, 4H), 7.22 (m, 1H), 7.30-7.42 (m, 2H), 8.43 (d, J=8.2Hz, 1H), 10.16 (br, 2H).

Embodiment 25

N-[2-(3,4-dichlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(3,4-dichlorophenoxy)-1-oil of mirbane (1.15g, 81%) is that (0.9g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 3,4-chlorophenesic acid.According to common processes B, it is reduced to 2-(3,4-dichlorophenoxy) aniline (0.69g, 68%).N-[2-(3,4-dichlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (129mg, 68%) be from 2-(3,4-dichlorophenoxy) aniline (127mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：382(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.99-7.13 (m, 4H), 7.24-7.28 (m, 2H), 7.30 (d, J=3.6Hz, 1H), 7.57 (d, J=9.2Hz, 1H), 8.44 (dd, J=8.4,1.2Hz, 1H), 9.20 (br, 1H), 10.09 (br, 1H).

Embodiment 26

N-[2-(4-chloro-3-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea

N-[2-(4-chloro-3-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea (233mg, 65%) be from 2-(4-chloro-3-methylphenoxy) aniline (233mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.36 (s, 3H), 6.94-6.98 (m, 2H), 7.05 (m, 4H), 7.19 (m, 1H), 7.31 (d, J=4.0Hz, 1H), 7.37 (d, J=8.4Hz, 1H), 8.43 (d, J=8.4Hz, 1H), 10.23 (br, 2H).

Embodiment 27

N-[2-(3,4-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(3,4-dimethoxy phenoxy group)-1-oil of mirbane (0.93g, 68%) is that (0.85g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 3,4-syringol.According to common processes B, it is reduced to 2-(3,4-dimethoxy phenoxy group) aniline (0.51g, 62%).N-[2-(3,4-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (128mg, 69%) be from 2-(3,4-dimethoxy phenoxy group) aniline (123mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：373(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.80 (s, 6H), 6.54 (dd, J=8.4,2.4Hz, 1H), 6.78 (d, J=2.4Hz, 1H), 6.82 (d, J=8.0Hz, 1H), 6.97 (d, J=8.0Hz, 1H), 6.99-7.01 (m, 1H), 7.04 (d, J=3.6Hz, 1H), 7.07-7.12 (m, 1H), 7.33-7.34 (d, J=3.6Hz, 1H), 8.39 (dd, J=8.0,1.2Hz, 1H), 8.90 (br, 1H), 10.23 (br, 1H).

Embodiment 28

N-[2-(3,4-methylenedioxybenzenes oxygen base) phenyl]-N '-(thiazol-2-yl) urea

2-(3,4-methylenedioxybenzenes oxygen base)-1-oil of mirbane (0.75g, 58%) is that (0.76g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 3,4-methylene-dioxy phenol.According to common processes B, it is reduced to 2-(3,4-methylenedioxybenzenes oxygen base) aniline (0.47g, 71%).N-[2-(3,4-methylenedioxybenzenes oxygen base) phenyl]-N '-(thiazol-2-yl) urea (120mg, 68%) is from 2-(3,4-methylenedioxybenzenes oxygen base) aniline (115mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：357(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.06 (s, 2H), 6.51 (dd, J=8.4,2.4Hz, 1H), 6.67 (d, J=2.4Hz, 1H), 6.84-6.87 (m, 2H), and 6.99-7.05 (m, 2H), 7.10-7.14 (m, 1H), and 7.32-7.33 (d, J=3.6Hz, 1H), 8.39 (dd, J=8.0,1.2Hz, 1H), 8.95 (br, 1H), 10.22 (br, 1H).

Embodiment 29

N-[2-(2,4 dichloro benzene oxygen base) phenyl]-N '-(thiazol-2-yl) urea

N-[2-(2,4 dichloro benzene oxygen base) phenyl]-N '-(thiazol-2-yl) urea (125mg, 67%) be from 2-(2,4 dichloro benzene oxygen base) aniline (127mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：382(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.86 (d, J=8.0Hz, 1H) 7.03-7.08 (m, 3H), 7.19-7.23 (m, 1H), 7.30 (d, J=4.0Hz, 1H), 7.38 (dd, J=8.8,2.8Hz, 1H), 7.65 (d, J=2.4Hz, 1H), 8.43 (dd, J=8.0,1.2Hz, 1H), 8.87 (br, 1H), 10.16 (br, 1H).

Embodiment 30

N-[2-(2,4 difluorobenzene oxygen base) phenyl]-N '-(thiazol-2-yl) urea

2-(2,4 difluorobenzene oxygen base)-1-oil of mirbane (0.95g, 76%) is that (0.72g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,4 difluorobenzene phenol.According to common processes B, it is reduced to 2-(2,4 difluorobenzene oxygen base) aniline (0.53g, 63%).N-[2-(2,4 difluorobenzene oxygen base) phenyl]-N '-(thiazol-2-yl) urea (120mg, 69%) be from 2-(2,4 difluorobenzene oxygen base) aniline (110mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：349(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.83 (m, 1H), 7.00-7.30 (m, 6H), 7.32 (d, J=3.6Hz, 1H), 8.42 (dd, J=8.0,2.0Hz, 1H), 9.00 (br, 1H), 10.19 (br, 1H).

Embodiment 31

N-[2-(4-fluoro-2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(4-fluoro-2-methoxyl group phenoxy group)-1-oil of mirbane (0.88g, 67%) is that (0.78g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 4-fluoro-2-methoxyphenol.According to common processes C, it is reduced to 2-(4-fluoro-2-methoxyl group phenoxy group) aniline (0.60g, 78%).N-[2-(4-fluoro-2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (127mg, 71%) be from 2-(4-fluoro-2-methoxyl group phenoxy group) aniline (116mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.82 (s, 3H), 6.61 (dd, J=8.0,2.8Hz, 1H), and 6.74-6.79 (m, 1H), 6.89-6.94 (m, 1H), 7.00-7.06 (m, 3H), 7.16 (dd, J=8.8,5.6Hz, 1H), 7.33 (d, J=3.6Hz, 1H), 8.43 (dd, J=8.4,1.6Hz, 1H), 8.85 (br, 1H), 10.29 (br, 1H).

Embodiment 32

N-[2-(4-methoxyl group-2-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-[4-methoxyl group-2-methoxycarbonyl phenoxy group]-1-oil of mirbane (0.78g, 52%) is that (1.0g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from methyl 5-methoxyl group salicylate.According to common processes B, it is reduced to 2-[4-methoxyl group-2-(methoxycarbonyl) phenoxy group] aniline (0.47g, 68%).N-[2-(4-methoxyl group-2-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (130mg, 66%) be from 2-[4-methoxyl group-2-(methoxycarbonyl) phenoxy group] aniline (136mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：401(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.69 (s, 3H), 3.84 (s, 3H), 6.61 (dd, J=8.0,1.6Hz, 1H), 6.90-6.95 (m, 1H), 7.03-7.09 (m, 2H), 7.16-7.25 (m, 2H), 7.25-7.39 (m, 1H), 7.43-7.44 (m, 1H), 8.37 (dd, J=8.4,1.6Hz, 1H), 8.96 (br, 1H), 10.26 (br, 1H).

Embodiment 33

N-[2-(3-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(3-methoxyl group phenoxy group)-1-oil of mirbane (0.84g, 69%) is that (0.68g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 3-methoxyphenol.According to common processes B, it is reduced to 2-(3-methoxyl group phenoxy group) aniline (0.51g, 70%).N-[2-(3-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (136mg, 68%) be from 2-(3-methoxyl group phenoxy group) aniline (108mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：343(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.78 (s, 3H), 6.55-6.62 (m, 2H), 6.71-6.73 (m, 1H), 6.95 (dd, J=8.0,1.6Hz, 1H), 7.03-7.07 (m, 2H), 7.16-7.20 (m, 1H), 7.27 (d, J=8.4Hz, 1H), 7.31 (d, J=4.0Hz, 1H), 8.43 (dd, J=8.4,1.6Hz, 1H), 8.84 (br, 1H), 10.37 (br, 1H).

Embodiment 34

N-[2-(3-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(3-fluorophenoxy)-1-oil of mirbane (0.85g, 73%) is that (0.62g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 3-fluorophenol.According to common processes B, it is reduced to 2-(3-fluorophenoxy) aniline (0.50g, 68%).N-[2-(3-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (110mg, 68%) be from 2-(3-fluorophenoxy) aniline (102mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：331(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.80-6.84 (m, 2H), 6.85-6.93 (m, 1H), 7.03-7.07 (m, 2H), 7.08-7.13 (m, 1H), 7.30 (d, J=3.6Hz, 1H), 7.38-7.45 (m, 1H), 8.45 (dd, J=8.0,1.2Hz, 1H), 9.06 (br, 1H), 10.1 (br 1H).

Embodiment 35

N-[2-(3-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea

2-[3-(trifluoromethyl) phenoxy group]-1-oil of mirbane (0.92g, 65%) is that (0.89g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 3-hydroxybenzotrifluoride.According to common processes B, it is reduced to 2-[3-(trifluoromethyl) phenoxy group] aniline (0.56g, 68%).N-[2-(3-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea (120mg, 62%) is from 2-[3-(trifluoromethyl) phenoxy group] aniline (127mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：381(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 7.04-7.13 (m, 3H), 7.24-7.29 (m, 3H), 7.36 (s, 1H), 7.47 (d, J=7.6Hz, 1H), 7.63 (t, J=8.0Hz, 1H), 8.46 (dd, J=8.0,1.2Hz, 1H), 8.95 (br, 1H), 10.08 (br, 1H).

Embodiment 36

N-[2-(2-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea

N-[2-(2-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea (110mg, 68%) be from 2-(2-methylphenoxy) aniline (100mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：327(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.25 (s, 3H), 6.68 (d, J=8.4Hz, 1H), 6.89 (d, J=8.0Hz, 1H), 6.96-7.00 (m, 1H), 7.04-7.13 (m, 3H), 7.20-7.34 (m, 3H), 8.42 (dd, J=8.0,1.6Hz, 1H), 8.95 (br, 1H), 10.25 (br, 1H).

Embodiment 37

N-[2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2-methoxyl group phenoxy group)-1-oil of mirbane (0.99g, 81%) is that (0.68g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 2-methoxyphenol.According to common processes B, it is reduced to 2-(2-methoxyl group phenoxy group) aniline (0.63g, 73%).N-2-(2-methoxyl group phenoxy group) phenyl-N '-(thiazol-2-yl) urea (110g, 65%) be from 2-(2-methoxyl group phenoxy group) aniline (108mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：343(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.78 (s, 3H), 6.61 (d, J=8.0Hz, 1H), 6.91-7.33 (m, 8H), 8.37 (d, J=8.0Hz, 1H), 9.13 (br, 1H), 10.31 (br, 1H).

Embodiment 38

N-[2-(2-isopropoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2-isopropoxy phenoxy group)-1-oil of mirbane (0.90g, 69%) is that (0.84g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 2-isopropoxy phenol.According to common processes B, it is reduced to 2-(2-methoxyl group phenoxy group) aniline (0.65g, 81%).N-[2-(2-isopropoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (120mg, 65%) be from 2-(2-isopropoxy phenoxy group) aniline (122mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：371(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.07 (d, J=6.0Hz, 6H), 4.54-4.59 (m, 1H), 6.64 (dd, J=8.0,1.6Hz, 1H), 6.88-6.92 (m, 1H), and 6.97-7.06 (m, 3H), 7.12-7.22 (m, 3H), 7.33 (d, J=3.6Hz, 1H), 8.38 (dd, J=8.0,1.6Hz, 1H), 8.86 (br, 1H), 10.3 (br, 1H).

Embodiment 39

N-[2-(2-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(2-fluorophenoxy)-1-oil of mirbane (0.94g, 81%) is that (0.62g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 2-fluorophenol.According to common processes B, it is reduced to 2-(2-fluorophenoxy) aniline (0.59g, 72%).N-[2-(2-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (110mg, 68%) be from 2-(2-fluorophenoxy) aniline (102mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS：331(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.84 (d, J=8.0Hz, 1H) 7.05-7.08 (m, 1H), 7.01-7.06 (m, 2H), 7.12-7.17 (m, 2H), and 7.22-7.25 (m, 2H), 7.29-7.36 (m, 2H), 8.43 (dd, J=8.0,1.6Hz, 1H), 8.95 (br, 1H), 10.17 (br, 1H).

Embodiment 40

N-[2-(2-methylthio group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2-methylthio group phenoxy group)-1-oil of mirbane (0.88g, 68%) is that (0.77g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2-hydroxyl thioanisole.According to common processes B, it is reduced to 2-(2-methylthio group phenoxy group) aniline (0.53g, 68%).N-[2-(2-methylthio group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (115mg, 65%) be from 2-(2-methylthio group phenoxy group) aniline (115mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：359(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.42 (s, 3H), 6.68 (dd, J=8.0,1.2Hz, 1H), 6.92 (d, J=8.0Hz, 1H), 6.95-6.99 (m, 1H), 7.04 (d, J=3.6Hz, 1H), 7.09-7.14 (m, 1H), 7.17-7.26 (m, 2H), 7.31 (d, J=3.6Hz, 1H), 7.38 (dd, J=7.6,1.6Hz, 1H), 8.42 (dd, J=8.0,1.6Hz, 1H), 8.95 (br, 1H), 10.26 (br, 1H).

Embodiment 41

N-[2-(2-methylsulfonyl phenoxy group) phenyl]-N '-thiazolyl urea

Under 0 ℃, to 2-(2-methylthio group phenoxy group)-1-oil of mirbane (1.3g, methylene dichloride 5.0mmol) (30mL) solution in 10min, add in batches mCPBA (70%, 3.68g, 15mmol).Content is at room temperature stirred 2h.Leach precipitation, mother liquor 10%aq Na ₂S ₂O ₃Wash three times.With organic layer washing (rare NaOH, water, salt solution), drying concentrates, and obtains 2-(2-methylsulfonyl phenoxy group)-1-oil of mirbane (1.0g, 68%).According to common processes B, it is reduced to 2-(2-methylsulfonyl phenoxy group) aniline (0.68g, 76%).N-[2-(2-methylsulfonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (105mg, 55%) be from 2-(2-methylsulfonyl phenoxy group) aniline (132mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：391(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.44 (s, 3H), 7.02 (d, J=3.6Hz, 1H), 7.06 (d, J=8.4Hz, 1H), 7.12-7.20 (m, 2H), 7.27-7.36 (m, 2H), 7.38-7.40 (m, 1H), 7.67-7.71 (m, 1H), 8.02 (dd, J=8.0,1.6Hz, 1H), 8.42 (dd, J=8.4,1.2Hz, 1H), 9.20 (br, 1H), 9.78 (br, 1H).

Embodiment 42

N-[2-(2-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea

2-[2-(trifluoromethyl) phenoxy group]-1-oil of mirbane (0.92g, 65%) is that (0.89g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from the 2-hydroxybenzotrifluoride.According to common processes B, it is reduced to 2-[2-(trifluoromethyl) phenoxy group] aniline (0.56g, 68%).N-[2-(2-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea (115mg, 61%) is from 2-[2-(trifluoromethyl) phenoxy group] aniline (127mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：381(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.91 (dd, J=8.0,1.6Hz, 1H), 7.01-7.06 (m, 2H), and 7.08-7.11 (m, 1H), 7.22-7.26 (m, 2H), 7.34 (t, J=7.6Hz, 1H), 7.65 (t, J=7.6Hz, 1H), 7.81 (dd, J=8.0,1.2Hz, 1H), 8.45 (dd, J=8.4,1.6Hz, 1H), 9.00 (br, 1H), 10.2 (br, 1H).

Embodiment 43

N-[2-(2,6-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2,6-dimethoxy phenoxy group)-1-oil of mirbane (0.85g, 63%) is that (0.85g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,6-syringol.According to common processes C, it is reduced to 2-(2,6-dimethoxy phenoxy group) aniline (0.51g, 68%).N-[2-(2,6-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (117g, 63%) be from 2-(2,6-dimethoxy phenoxy group) aniline (123mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：373(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.76 (s, 3H), 6.49 (dd, J=8.4,1.2Hz, 1H), 6.80 (d, J=8.4Hz, 2H), 6.84-6.88 (m, 1H), and 6.95-6.99 (m, 1H), 7.04 (d, J=3.2Hz, 1H), 7.22 (t, J=8.4Hz, 1H), 7.35 (d, J=3.6Hz, 1H), 8.33 (dd, J=8.0,1.6Hz, 1H), 8.85 (br, 1H), 10.40 (br, 1H).

Embodiment 44

N-[2-(2,6-, two fluorophenoxies) phenyl]-N '-(thiazol-2-yl) urea

2-(2,6-, two fluorophenoxies)-1-oil of mirbane (0.44g, 70%) is that (0.32g, 2.5mmol) (0.36g 2.5mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,6-difluorophenol.According to common processes B, it is reduced to 2-(2,6-, two fluorophenoxies) aniline (0.24g, 60%).N-[2-(2,6-, two fluorophenoxies) phenyl]-N '-(thiazol-2-yl) urea (133mg, 60%) be from 2-(2,6-, two fluorophenoxies) aniline (206mg, 0.9mmol) and thiazolamine (405mg is 2.5mmol) according to common processes D preparation.

LC-MS(m/z)：349(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.73 (d, J=8Hz, 1H), 6.98 (m, 1H), 7.06 (d, J=3.2Hz, 1H), 7.12 (m, 1H), 7.20-7.28 (m, 2H), 7.25 (d, J=3.6Hz, 1H), 7.40 (m, 1H), 8.43 (d, J=8.2Hz, 1H), 9.05 (br, 1H), 10.12 (br, 1H).

Embodiment 45

N-[2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2-fluoro-6-methoxyl group phenoxy group)-1-oil of mirbane (0.84g, 64%) is that (0.78g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2-fluoro-6-methoxyphenol.According to common processes C, it is reduced to 2-(2-fluoro-6-methoxyl group phenoxy group) aniline (0.63g, 85%).N-(2-(2-fluoro-6-methoxyl group phenoxy group) phenyl)-N '-(thiazol-2-yl) urea (114mg, 63%) be from 2-(2-fluoro-6-methoxyl group phenoxy group) aniline (117mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.82 (s, 3H), 6.59 (m, 1H), 6.89-6.96 (m, 2H), 7.02-7.07 (m, 3H), 7.27-7.33 (m, 1H), 7.34 (d, J=3.6Hz, 1H), 8.38 (dd, J=8.4,1.6Hz, 1H), 8.85 (br, 1H), 10.31 (br, 1H).

Embodiment 46

N-[2-(2-methoxyl group-6-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2-methoxyl group-6-methoxycarbonyl phenoxy group)-1-oil of mirbane (1.24g, 82%) is that (1.0g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from methyl 3-methoxyl group salicylate.According to common processes C, this compound is reduced to 2-(2-methoxyl group-6-methoxycarbonyl phenoxy group) aniline (0.89g, 80%).N-[2-(2-methoxyl group-6-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (143mg, 72%) be from 2-(2-methoxyl group-6-methoxycarbonyl phenoxy group) aniline (136mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：401(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.78 (s, 3H), 3.87 (s, 3H), 6.89-6.97 (m, 1H), 7.04-7.23 (m, 3H), 7.36-7.47 (m, 2H), 7.67-7.76 (m, 2H), 8.17 (dd, J=1.6,10.8Hz, 1H), 8.78 (br, 1H), 10.64 (br, 1H).

Embodiment 47

N-[(3-methoxyl group-2-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(3-methoxyl group-2-methoxycarbonyl phenoxy group)-1-oil of mirbane (1.21g, 80%) is that (1.09g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from methyl 6-methoxyl group salicylate.According to common processes C, this compound is reduced to 2-(3-methoxyl group-2-methoxycarbonyl phenoxy group) aniline (0.82g, 75%).N-[(3-methoxyl group-2-methoxycarbonyl phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (130mg, 65%) be from 2-(3-methoxyl group-2-methoxycarbonyl phenoxy group) aniline (136mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：401(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.66 (s, 3H), 3.80 (s, 3H), 6.44-6.46 (m, 1H), and 6.83-6.87 (m, 1H), 6.96-6.99 (m, 1H), 7.03 (d, J=3.6Hz, 1H), 7.33 (d, J=4Hz, 1H), and 7.37-7.46 (m, 2H), 7.46-7.48 (m, 1H), 8.32-8.35 (dd, J=1.6,8.0Hz, 1H), 8.80 (br, 1H), 10.32 (br, 1H).

Embodiment 48

N-[2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

2-(2,3-dimethoxy phenoxy group)-1-oil of mirbane (0.88g, 64%) is that (0.85g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,3-syringol.According to common processes B, it is reduced to 2-(2,3-dimethoxy phenoxy group) aniline (0.57g, 73%).N-[2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (131g, 71%) be from 2-(2,3-dimethoxy phenoxy group) aniline (123mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：373(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.66 (s, 3H), 3.88 (s, 3H), 6.66-6.74 (m, 2H), 6.91-6.98 (m, 2H), 7.04-7.16 (m, 3H), 7.32 (d, J=3.6Hz, 1H), 8.39 (dd, J=8.0,1.6Hz, 1H), 8.90 (br, 1H), 10.26 (br, 1H).

Embodiment 49

N-[2-(2,3,4-Trichlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(2,3,4-Trichlorophenoxy)-1-oil of mirbane (1.04g, 65%) is that (0.98g, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,3,4-Trichlorophenol.According to common processes B, it is reduced to 2-(2,3,4-Trichlorophenoxy) aniline (0.42g, 60%, 2.5mmol scale).N-[2-(2,3,4-Trichlorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (343mg, 55%) be from 2-(2,3,4-Trichlorophenoxy) aniline (420mg, 1.5mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：415(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 9.97-7.12 (m, 4H), 7.23-7.28 (m, 2H), 7.58 (d, J=8.8Hz, 1H), 8.45 (d, J=8.0Hz, 1H), 10.13 (br, 1H).

Embodiment 50

N-[2-(2,4,6-trifluoromethoxy phenoxy base) phenyl]-N '-(thiazol-2-yl) urea

2-(2,4,6-trifluoromethoxy phenoxy base)-1-oil of mirbane (1.14g, 85%) is that (0.74g, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,4,6-trifluoromethyl phenol.According to common processes B, it is reduced to 2-(2,4,6-trifluoromethoxy phenoxy base) aniline (0.42g, 70%, 2.5mmol scale).N-[2-(2,4,6-trifluoromethoxy phenoxy base) phenyl]-N '-(thiazol-2-yl) urea (219mg, 60%) be from 2-(2,4,6-trifluoromethoxy phenoxy base) aniline (237mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：367(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.78 (d, J=8.4Hz, 1H), 7.00-7.21 (m, 5H), 7.36 (d, J=3.6Hz, 1H), 8.42 (d, J=8.4Hz, 1H), 9.05 (br, 1H), 10.36 (br, 1H).

Embodiment 51

N-[2-(2,4-dichloronaphtalene-1-oxygen base) phenyl]-N '-(thiazol-2-yl) urea

2-(2,4-dichloronaphtalene-1-oxygen base)-1-oil of mirbane (1.17g, 60%) is that (1.06g, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes A with 1-fluoro-2-oil of mirbane from 2,4-dichloronaphtalene-1-phenol.According to common processes B, it is reduced to 2-(2,4-dichloronaphtalene-1-oxygen base) aniline (0.45g, 60%, 2.5mmol scale).N-[2-(2,4-dichloronaphtalene-1-oxygen base) phenyl]-N '-thiazolyl urea (172g, 40%) be from 2-(2,4-dichloronaphtalene-1-oxygen base) aniline (303mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：431(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.39 (d, J=8.2Hz, 1H), 6.86 (m, 1H), 7.07 (m, 2H), 7.34 (d, J=3.6Hz, 1H), 7.71-7.88 (m, 3H), 8.00 (d, J=8.0Hz, 1H), 8.32 (d, J=8.0Hz, 1H), 8.48 (d, J=8.0Hz, 1H), 9.15 (br, 1H), 10.35 (br, 1H).

Embodiment 52

N-[2-(2-methoxyl group phenoxy group)-5-(methylsulfonyl) phenyl]-N '-(thiazol-2-yl) gland

2-(2-methoxyl group phenoxy group)-5-(methylsulfonyl)-1-oil of mirbane (1.21g, 75%) is that (0.68g, 5.5mmol) (1.09g 5.0mmol) prepares according to common processes A with 1-fluoro-4-methylsulfonyl-2-oil of mirbane from the 2-methoxyphenol.According to common processes B, it is reduced to 2-(2-methoxyl group phenoxy group)-5-(methylsulfonyl) aniline (0.68g, 62%).N-[2-(2-methoxyl group phenoxy group)-5-(methylsulfonyl) phenyl]-N '-(thiazol-2-yl) urea (136mg; 65%) be from 2-(2-methoxyl group phenoxy group)-5-(methylsulfonyl) aniline (146mg; 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：421(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.82 (s, 3H), 3.77 (s, 3H), 6.73 (d, J=8.4Hz, 1H) 7.05-7.11 (m, 2H), 7.23-7.28 (m, 2H), 7.32-7.37 (m, 2H), 7.50 (dd, J=8.4,3.6Hz, 1H), 9.02 (d, J=2.4Hz, 1H), 9.12 (br, 1H), 10.42 (br, 1H).

Embodiment 53

N-[5-cyano group-2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

4-(2-methoxyl group phenoxy group)-3-nitrobenzonitrile (1.10g, 81%) is that (0.68g, 5.5mmol) (1.33g 5.0mmol) prepares according to common processes A with 4-fluoro-3-nitrobenzonitrile from the 2-methoxyphenol.According to common processes B, it is reduced to 4-(2-methoxyl group phenoxy group)-3-aminobenzonitrile (0.62g, 63%).N-[5-cyano group-2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (130mg, 71%) be from 4-(2-methoxyl group phenoxy group)-3-aminobenzonitrile (120mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：368(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.79 (s, 3H), 6.69 (d, J=8.4Hz, 1H) 7.05-7.09 (m, 1H), 7.10 (d, J=3.6Hz, 1H), 7.22-7.27 (m, 2H), 7.32-7.36 (m, 3H), 8.75 (d, J=2.0Hz, 1H), 9.12 (br, 1H), 10.38 (br, 1H).

Embodiment 54

N-[5-fluoro-2-(2-methylthio group phenoxy group) phenyl]-N '-thiazolyl urea

5-fluoro-2-(2-methylthio group phenoxy group)-1-oil of mirbane (0.95g, 68%) is that (0.77g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from 2-hydroxyl thioanisole.According to common processes B, it is reduced to 5-fluoro-2-(2-methylthio group phenoxy group) aniline (0.52g, 62%).N-[5-fluoro-2-(2-methylthio group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (120mg, 65%) be from 5-fluoro-2-(2-methylthio group phenoxy group) aniline (125mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：377(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.48 (s, 3H), 6.61 (m, 2H), 6.92 (d, J=7.6Hz, 1H), 7.06 (d, J=3.6Hz, 1H), 7.16-7.25 (m, 2H), 7.31 (d, J=3.6Hz, 1H), 7.39 (dd, J=7.6,2.0Hz, 1H), 8.26-8.29 (m, 1H), 9.00 (br, 1H), 10.32 (br, 1H).

Embodiment 55

N-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group)-1-oil of mirbane (0.91g, 65%) is that (0.78g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from 2-fluoro-6-methoxyphenol.According to common processes C, it is reduced to 5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) aniline (0.66g, 81%).N-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (130g, 69%) be from 5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) aniline (126mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：379(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.83 (s, 3H), 6.60-6.70 (m, 2H), 6.92-6.97 (m, 1H), 7.03-7.05 (m, 1H), 7.09 (d, J=4.0Hz, 1H), 7.27-7.33 (m, 1H), 7.36 (d, J=3.6Hz, 1H), 8.23 (dd, J=10.8,3.2Hz, 1H), 9.05 (br, 1H), 10.39 (br, 1H).

Embodiment 56

N-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl]-N ' (thiazol-2-yl) urea

2-(2,3-dimethoxy phenoxy group)-5-fluoro-1-oil of mirbane (1.0g, 68%) is that (0.85g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from 2,3-syringol.According to common processes C, it is reduced to 2-(2,3-dimethoxy phenoxy group)-5-fluoroaniline (0.67g, 75%).N-[2-(2,3-dimethoxy phenoxy group)-the 5-fluorophenyl]-N '-(thiazol-2-yl) urea (126g, 65%) is from 2-(2,3-dimethoxy phenoxy group)-5-fluoroaniline (132mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：391(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.68 (s, 3H), 3.88 (s, 3H), 6.67 (dd, J=9.2,1.2Hz, 1H), 6.70-6.79 (m, 2H), 6.92 (dd, J=8.0,1.6Hz, 1H), 7.05-7.09 (m, 2H), 7.32 (d, J=3.6Hz, 1H), 8.25 (dd, J=11.2,2.8Hz, 1H), 9.03 (br, 1H), 10.33 (br, 1H).

Embodiment 57

N-[2-(3,4-, two fluorophenoxies)-5-fluorophenyl]-N '-(thiazol-2-yl) urea

2-(3,4-, two fluorophenoxies)-5-fluoro-1-oil of mirbane (1.05g, 78%) is that (0.72g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from 3,4-difluorophenol.According to common processes B, this compound is reduced to 2-(3,4-, two fluorophenoxies)-5-fluoroaniline (0.63g, 68%).N-[2-(3,4-two fluorophenoxies)-the 5-fluorophenyl]-N '-(thiazol-2-yl) urea (132mg, 72%) is from 2-(3,4-, two fluorophenoxies)-5-fluoroaniline (120mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：367(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.81-6.89 (m, 2H), 7.05-7.11 (m, 3H), 7.31-7.38 (m, 2H), 8.28 (dd, J=2.8,10.8Hz, 1H), 9.10 (br, 1H), 10.34 (br, 1H).

Embodiment 58

N-[5-fluoro-2-(4-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea

5-fluoro-2-(4-fluorophenoxy)-1-oil of mirbane (0.94g, 75%) is that (0.62g, 5.5mmol) with 2, (0.71g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from the 4-fluorophenol.According to common processes B, this compound is reduced to 2-(4-fluorophenoxy)-5-fluoroaniline (0.53g, 64%).N-[5-fluoro-2-(4-fluorophenoxy) phenyl]-N '-(thiazol-2-yl) urea (130mg, 75%) be from 5-fluoro-2-(4-fluorophenoxy) aniline (110mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：349(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.78-6.82 (m, 1H), 6.93-6.97 (m, 1H), 7.06-7.10 (m, 3H), 7.14-7.18 (m, 2H), 7.3 (d, J=3.2Hz, 1H), 8.27 (dd, J=2.8,10.8Hz, 1H), 8.82 (br, 1H), 10.28 (br, 1H).

Embodiment 59

N-[2-(2,4 dichloro benzene oxygen base)-5-fluorophenyl]-N '-(thiazol-2-yl) urea

2-(2,4 dichloro benzene oxygen base)-5-fluoro-1-oil of mirbane (1.17g, 78%) is that (0.89g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from 2,4 dichloro phenol.According to common processes B, this compound is reduced to 2-(2,4 dichloro benzene oxygen base)-5-fluoroaniline (0.68g, 64%).N-[2-(2, the 4-dichlorophenoxy)-the 5-fluorophenyl]-N '-(thiazol-2-yl) urea (150mg, 76%) is from 2-(2,4 dichloro benzene oxygen base)-5-fluoroaniline (135mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：399(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.79-6.84 (m, 1H), 6.93 (m, 1H), 7.03-7.07 (m, 2H), 7.30 (d, J=3.2Hz, 1H), 7.38 (dd, 2.4,8.8Hz 1H), 7.64 (d, J=2.4Hz, 1H), (8.29 dd, J=2.4,11.2Hz 1H), 9.00 (br, 1H), 10.24 (bs, 1H).

Embodiment 60

N-[5-fluoro-2-(4-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

5-fluoro-2-(4-methoxyl group phenoxy group)-1-oil of mirbane (1.05g, 80%) is that (0.68g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from the 4-methoxyphenol.According to common processes B, this compound is reduced to 5-fluoro-2-(4-methoxyl group phenoxy group) aniline (0.62g, 66%).N-[5-fluoro-2-(4-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (133mg, 74%) be from 2-(4-methoxyl group phenoxy group)-5-fluoroaniline (117mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.79 (s, 3H), 6.75-6.77 (m, 1H), 6.82-6.87 (m, 1H), 6.94-7.01 (m, 3H), 7.07 (d, J=2.1Hz, 1H), 7.32 (d, J=3.6Hz, 1H), 8.26 (dd, J=3.2,11.2Hz, 1H), 9.05 (br, 1H), 10.32 (br, 1H).

Embodiment 61

N-[5-fluoro-2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

5-fluoro-2-(2-methoxyl group phenoxy group)-1-oil of mirbane (1.07g, 81%) is that (0.62g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from the 2-methoxyphenol.According to common processes B, this compound is reduced to 2-(2-methoxyl group phenoxy group)-5-fluoroaniline (0.58g, 66%).1-[5-fluoro-2-(2-methoxyl group phenoxy group) phenyl]-3-(thiazol-2-yl) urea (129mg, 72%) be from 5-fluoro-2-(2-methoxyl group phenoxy group) aniline (117mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.79 (s, 3H), 6.65-6.7 (m, 2H), 6.98-7.01 (m, 1H), 7.05-7.22 (m, 4H), 7.32 (d, J=3.6Hz, 1H), 8.22 (dd, J=2.8,10.8Hz, 1H), 9.12 (br, 1H), 10.42 (br, 1H).

Embodiment 62

N-[5-fluoro-2-(2-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea

5-fluoro-2-(2-4-trifluoromethylphenopendant)-1-oil of mirbane (1.17g, 78%) is that (0.89g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from the 2-hydroxybenzotrifluoride.According to common processes B, this compound is reduced to 5-fluoro-2-(2-4-trifluoromethylphenopendant)-aniline (0.65g, 62%).N-[5-fluoro-2-(2-4-trifluoromethylphenopendant) phenyl]-N '-(thiazol-2-yl) urea (146mg, 74%) be from 2-(2-4-trifluoromethylphenopendant)-5-fluoroaniline (135mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：399(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.81-6.87 (m, 1H), 6.95-7.05 (m, 3H), 7.21 (m, 1H), 7.31-7.36 (m, 1H), 7.6-7.65 (m, 1H), 7.79 (d, J=7.6Hz, 1H), 8.30 (dd, J=3.2,11.2Hz, 1H), 8.72 (br, 1H), 10.24 (br, 1H).

Embodiment 63

N-[5-fluoro-2-(naphthalene-2-oxygen base) phenyl]-N '-(thiazol-2-yl) urea

5-fluoro-2-(naphthalene-2-oxygen base)-1-oil of mirbane (1.13g, 80%) is that (0.79g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes A 5-two fluoro-1-oil of mirbane from beta naphthal.According to common processes B, this compound is reduced to 2-(2-naphthalene-2-oxygen base)-5-fluoroaniline (0.64g, 64%).N-[5-fluoro-2-(naphthalene-2-oxygen base) phenyl]-N '-(thiazol-2-yl) urea (123mg, 65%) be from 5-fluoro-2-(naphthalene-2-oxygen base)-aniline (127mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：381(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.83-6.87 (m, 1H), 7.01 (bs, 1H), 7.08 (m, 1H), 7.33 (bs, 1H), 7.42-7.49 (m, 3H), 7.80 (d, J=7.6Hz, 1H), 7.90 (d, J=7.6Hz, 1H), 7.97 (d, J=8.8Hz, 1H), 8.32 (d, J=8.4Hz, 1H), 8.62 (br, 1H), 10.22 (br, 1H)

Embodiment 64

N-[2-(2,3-dimethoxy phenoxy group)-6-fluorophenyl]-N '-(thiazol-2-yl) urea

2-(2,3-dimethoxy phenoxy group)-6-fluoro-oil of mirbane (1.05g, 72%) is that (0.85g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A the 6-difluoro nitrobenzene from 2,3-syringol.According to common processes C, this compound is reduced to 2-(2,3-dimethoxy phenoxy group)-6-fluoroaniline (0.66g, 7 0%).N-[2-(2,3-dimethoxy phenoxy group)-the 6-fluorophenyl]-N '-(thiazol-2-yl) urea (136mg, 70%) is from 2-(2,3-dimethoxy phenoxy group)-6-fluoroaniline (131mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：391(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.64 (s, 3H), 3.85 (s, 3H), 6.59 (d, J=8.0Hz, 1H), 6.68-6.69 (d, J=8.0Hz, 1H), 6.88-7.06 (m, 4H), 7.22-7.22 (m1H), 7.30-7.31 (d, J=3.2Hz, 1H), 8.18 (br, 1H), 10.26 (br, 1H).

Embodiment 65

N-[2-(4-fluoro-2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

4-fluoro-2-(2-methoxyl group phenoxy group)-1-oil of mirbane (1.2g, 91.6%) is that (0.68g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes F 4-two fluoro-1-oil of mirbane from the 2-methoxyphenol.According to common processes B, product is reduced to 4-fluoro-2-(2-methoxyl group phenoxy group) aniline (0.96g, 73%).N-[4-fluoro-2-(2-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (0.32g, 86%) be from 4-fluoro-2-(2-methoxyl group phenoxy group) aniline (0.117g, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H?NMR(400MHz，CDCl ₃)：δ3.78(s，3H)，6.32(dd，J＝4.0，14.0Hz，1H)，6.35(dd，J＝2.8，10.4Hz，1H)，6.61(t，J＝4.0Hz，1H)，6.80(m，2H)，7.05(m，2H)，7.18(m，2H)，11.46(br，2H).

Embodiment 66

N-[2-(2,3-dimethoxy phenoxy group)-4-fluorophenyl]-N '-(thiazol-2-yl) urea

2-(2,3-dimethoxy phenoxy group)-4-fluoro-1-oil of mirbane (0.88g, 60%) is that (0.85g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes F 4-two fluoro-1-oil of mirbane from 2,3-syringol.According to common processes C, this compound is reduced to 2-(2,3-dimethoxy phenoxy group)-4-fluoroaniline (0.52g, 66%).N-[2-(2,3-dimethoxy phenoxy group)-the 4-fluorophenyl]-N '-(thiazol-2-yl) urea (116mg, 60%) is from 2-(2,3-dimethoxy phenoxy group)-4-fluoroaniline (132mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：391(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.68 (s, 3H), 3.89 (s, 3H), 6.46 (dd, J=2.4,9.2Hz, 1H), 6.76 (dd, J=1.6,8.0Hz, 1H), 6.82-6.87 (m, 1H), 6.98 (dd, J=2.3,6.8Hz, 1H), 7.04 (d, J=3.6Hz, 1H), 7.1-7.13 (t, J=8.4Hz, 1H), 7.31 (d, J=4.0Hz, 1H), 8.33-8.37 (dd, J=6.4,9.6Hz, 1H), 8.42 (br, 1H), 10.23 (br, 1H).

Embodiment 67

N-[4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group)-1-oil of mirbane (0.91g, 65%) is that (0.78g, 5.5mmol) with 2, (0.8g 5.0mmol) prepares according to common processes F 4-two fluoro-1-oil of mirbane from 2-fluoro-6-methoxyphenol.According to common processes C, this compound is reduced to 4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) aniline (0.61g, 75%).N-[4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (122mg, 65%) be from 4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) aniline (126mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：379(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.84 (s, 3H), 6.39 (dd, 2.8,9.6Hz 1H), 6.81-6.85 (m, 1H), 6.95-6.98 (m, 1H), 7.05-7.07 (m, 2H) 7.29-7.35 (m, 2H), 8.32-8.36 (m, 1H), 8.85 (br, 1H), 10.26 (br, 1H)

Embodiment 68

N-[2-(2-fluoro-6-methoxyl group phenoxy group)-4-p-methoxy-phenyl]-N '-(thiazol-2-yl) urea

(1.33g, 5mmol) (0.35g, 6mmol) mixture in DMF (10mL) heats 2h down at 80 ℃ with sodium methylate with 4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group)-1-oil of mirbane.Mixture is poured in the water, with ethyl acetate extraction (3 * 20mL).Merge organic layer, water, salt water washing, dry (Na ₂SO ₄).Under reduced pressure concentrated solution obtains 2-(2-fluoro-6-methoxyl group phenoxy group)-4-methoxyl group-1-oil of mirbane (1.02g, 70%).According to common processes C, this compound is reduced to 2-(2-fluoro-6-methoxyl group phenoxy group)-4-anisidine (0.62g, 73%).N-[2-(2-fluoro-6-methoxyl group phenoxy group)-4-p-methoxy-phenyl]-N '-(thiazol-2-yl) urea (136mg, 70%) be from 2-(2-methoxyl group-6-fluorophenoxy)-4-anisidine (132mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：391(M+1) ⁺.

¹H?NMR(400MHz，CDCl ₃)：δ3.74(s，3H)，6.19(bs，1H)，6.46(dd，J＝2.4，7.6Hz，1H)，6.61-6.84(m，3H)，7.04-7.19(m，1H)，7.32-7.44(bs，1H)，8.04-8.12(m，1H)，8.20(br，1H)，10.22(br，1H).

Embodiment 69

N-[3-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

Methyl 3-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) benzoic ether (0.88g, 60%) is from methyl 2, and (0.86g, 5mmol) (0.78g 5.5mmol) prepares described in technology A 3-difluoro-benzoic acid ester with 2-fluoro-6-methoxyphenol.In aqueous methanol, with the LiOH hydrolysis of this ester, obtain 2-(2-methoxyl group-6-fluorophenoxy)-3-fluorobenzoic acid (0.86g, 90%).To 3-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenylformic acid (0.56g, 2.0mmol) 1,2-ethylene dichloride (10mL) solution add oxalyl chloride (0.18mL, 2.2mmol).Solution is at room temperature stirred 45min.Add NaN to this solution ₃(390mg 6mmol), reaches mixture heating up at 3h to refluxing.(200mg 2mmol), advances-goes on foot backflow 3h to add thiazolamine to this mixture then.Enriched mixture, resistates is through column chromatography purifying (silicon-dioxide, CH ₂Cl ₂, contain the CH of 10% ethyl acetate then ₂Cl ₂), obtain 1-[3-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl]-3-(thiazol-2-yl) urea (414mg, 55%).

LC-MS(m/z)：379(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.72 (s, 3H), 6.44 (d, J=8.4Hz, 1H), 6.69-6.84 (m, 4H), 7.01-7.12 (m, 2H), 7.35-7.36 (d, J=4.0Hz, 1H), 8.28 (br, 1H), 10.28 (br, 1H).

Embodiment 70

N-[2-(2,3-dimethoxy phenoxy group)-5-p-methoxy-phenyl]-N '-thiazol-2-yl urea

2-(2,3-dimethoxy phenoxy group)-5-methoxyl group-1-oil of mirbane (0.85g, 56%) is that (0.85g, 5.5mmol) (0.94g 5.0mmol) prepares according to common processes A with 4-chloro-3-nitroanisole from 2,3-syringol.According to common processes C, it is reduced to 2-(2,3-dimethoxy phenoxy group)-5-anisidine (0.65g, 85%).N-[2-(2,3-dimethoxy phenoxy group)-the 5-p-methoxy-phenyl]-N '-(thiazol-2-yl) urea (124g, 62%) is from 2-(2,3-dimethoxy phenoxy group)-5-anisidine (133mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：403(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.70 (s, 3H), 3.79 (s, 3H), 3.87 (s, 3H), and 6.53-6.57 (m, 2H), 6.75 (d, J=8.8Hz, 1H), 6.85 (dd, J=8.4,1.2Hz, 1H), 7.00 (d, J=8.4Hz, 1H), 7.04 (d, J=3.6Hz, 1H), 7.30 (d, J=3.6Hz, 1H), 8.10 (d, J=3.6Hz, 1H), 10.26 (br, 1H).

Embodiment 71

N-[2-(2,3-dimethoxy phenoxy group)-4-aminomethyl phenyl]-N '-(thiazol-2-yl) urea

3-(2,3-dimethoxy phenoxy group)-4-nitrotoluene (0.92g, 64%) is that (0.85g, 5.5mmol) (0.78g 5.0mmol) prepares according to common processes A with 3-fluoro-4-nitrotoluene from 2,3-syringol.According to common processes C, it is reduced to 2-(2,3-dimethoxy phenoxy group)-4-monomethylaniline (0.65g, 79%).N-[2-(2,3-dimethoxy phenoxy group)-the 4-aminomethyl phenyl]-N '-(thiazol-2-yl) urea (120mg, 63%) is from 2-(2,3-dimethoxy phenoxy group)-4-monomethylaniline (130mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：387(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.20 (s, 3H), 3.67 (s, 3H), 3.88 (s, 3H) 6.57 (d, J=1.2Hz, 1H), 6.64 (dd, J=8.4,1.6Hz, 1H), and 6.89-6.92 (m, 2H), 7.01-7.08 (m, 2H), 7.31 (d, J=3.6Hz, 1H), 8.24 (d, J=8.4Hz, 1H), 8.60 (br, 1H), 10.23 (br, 1H).

Embodiment 72

N-[2-(2,3-dimethoxy phenoxy group)-3-aminomethyl phenyl]-N '-(thiazol-2-yl) urea

2-(2,3-dimethoxy phenoxy group)-3-nitrotoluene (0.80g, 56%) is that (0.85g, 5.5mmol) (0.85g 5.0mmol) prepares according to common processes A with 2-chloro-3-nitrotoluene from 2,3-syringol.According to common processes C, it is reduced to 2-(2,3-dimethoxy phenoxy group)-3-monomethylaniline (0.54g, 76%).N-[2-(2,3-dimethoxy phenoxy group)-the 3-aminomethyl phenyl]-N '-(thiazol-2-yl) urea (116mg, 61%) is from 2-(2,3-dimethoxy phenoxy group)-3-monomethylaniline (130mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：387(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.09 (s, 3H), 3.88 (s, 6H), 6.07 (dd, J=8.4,1.2Hz, 1H), 6.73 (dd, J=8.4,1.2Hz, 1H), and 6.85-6.89 (m, 1H), 6.98-7.00 (m, 2H), and 7.16-7.20 (m, 1H), 7.24 (d, J=3.6Hz, 1H), 8.27 (d, J=8.0Hz, 1H), 8.95 (br, 1H), 10.09 (br, 1H).

Embodiment 73

N-[2-(2-chlorophenoxy)-5-chloro-phenyl-]-N '-(thiazol-2-yl) urea

N-[2-(2-chlorophenoxy)-5-chloro-phenyl-]-N '-(thiazol-2-yl) urea (119mg, 63%) be from 2-(2-chlorophenoxy)-5-chloroaniline (127mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：381(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.76 (d, J=8.4Hz, 1H), 7.04 (dd, J=8.4,2.4Hz, 1H), 7.07 (d, J=3.6Hz, 1H), 7.17 (d, J=8.4Hz, 1H), 7.24-7.42 (m, 3H), 7.59 (dd, J=8.0,1.6Hz, 1H), 8.55 (d, J=2.4Hz, 1H), 9.01 (br, 1H), 10.28 (br, 1H).

Embodiment 74

N-[5-chloro-2-(4-chloro-3-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea

N-[5-chloro-2-(4-chloro-3-methylphenoxy) phenyl]-N '-(thiazol-2-yl) urea (236mg, 60%) be that (2-methyl-3-chlorophenoxy)-the 5-chloroaniline is (commercial available from 2-, 268mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：397(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.35 (s, 3H), 6.90-7.02 (m, 2H), 7.06-7.10 (m, 3H), 7.32 (d, J=3.6Hz, 1H), 7.40 (d, J=8.8Hz, 1H), 8.54 (d, J=2.4Hz, 1H), 10.22 (br, 2H).

Embodiment 75

N-[2-(4-chlorophenoxy)-5-(trifluoromethyl) phenyl]-N '-(thiazol-2-yl) urea

N-[2-(4-chlorophenoxy)-5-(trifluoromethyl) phenyl]-N '-(thiazol-2-yl) urea (136mg, 66%) be from 2-(4-chlorophenoxy)-5-(trifluoromethyl) aniline (144mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：415(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 5.12 (br, 1H), 7.02 (d, J=9Hz, 1H), 7.09 (d, J=3.6Hz, 1H), 7.21 (d, J=8.8Hz, 2H), 7.34 (d, J=3.6Hz, 1H), 7.39 (d, J=8.8Hz, 1H), 7.49 (d, J=8.8Hz, 2H), 8.85 (d, J=1.5Hz, 1H), 8.95 (br, 1H), 10.29 (br, 1H).

Embodiment 76

N-[4,5-two fluoro-2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

4,5-, two fluoro-2-(2,3-dimethoxy phenoxy group)-1-oil of mirbane (1.4g, 90.3%) is that (0.85g, 5.5mmol) with 1,3, (0.885g 5.0mmol) prepares according to common processes F the 4-trifluoronitrobenzene from 2,3-syringol.According to common processes B, product is reduced to 2-(2-methoxyl group phenoxy group)-4,5-difluoroaniline (1.35g, 96.1%) then.N-[4,5-two fluoro-2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (0.181g, 89%) be from 2-(2,3-dimethoxy phenoxy group)-4, the 5-difluoroaniline (0.140g, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：361(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.71 (s, 3H), 3.88 (s, 3H), 6.63 (dd, J=1.6,8.4Hz, 1H), 6.89 (dd, J=1.2,6.4Hz, 1H), and 7.03-7.11 (m, 2H), 7.38 (d, J=3.6Hz, 1H), 8.26 (dd, J=1.6Hz, 7.6Hz, 1H), 8.42 (dd, J=1.2Hz, 7.2Hz, 1H), 9.13 (br, 1H), 10.22 (br, 1H).

Embodiment 77

N-[4,5-two chloro-2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea

4,5-, two chloro-2-(2,3-dimethoxy phenoxy group)-1-oil of mirbane (1.12g, 65%) is that (0.85g, 5.5mmol) with 4, (1.05g 5.0mmol) prepares according to common processes A 5-two chloro-2-fluoro-1-oil of mirbane from 2,3-syringol.According to common processes B, it is reduced to 4,5-, two chloro-2-(2,3-dimethoxy phenoxy group) aniline (0.68g, 67%).N-[4,5-two chloro-2-(2,3-dimethoxy phenoxy group) phenyl]-N '-(thiazol-2-yl) urea (136mg, 62%) be from 4,5-, two chloro-2-(2,3-dimethoxy phenoxy group) aniline (157mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：441(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.70 (s, 3H), 3.91 (s, 3H), 6.81-6.83 (m, 2H), 7.01 (dd, J=8.4,1.2Hz, 1H), 7.09 (d, J=3.6Hz, 1H), 7.15 (t, J=8.4Hz, 1H), 7.34 (d, J=3.6Hz, 1H), 8.65 (s, 1H), 8.95 (br, 1H), 10.36 (br, 1H).

Embodiment 78

N-[5-chloro-2-(2,3-dimethoxy phenoxy group)-4-dimethylamino phenyl]-N '-(thiazol-2-yl) urea

In the bottle of sealing, (0.35g, 1.0mmol) (4mL is 2M) at 80 ℃ of heating 48h down with the tetrahydrofuran solution of dimethylamine with 4,5-, two chloro-2-(2,3-dimethoxy phenoxy group)-1-oil of mirbane.Reaction mixture is cooled to room temperature, is dissolved in ethyl acetate (15mL).With solution washing (water, salt solution), concentrate, obtain required oil of mirbane, according to common processes B, it is reduced to 5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(dimethylamino) aniline (0.23g, 73%).N-[5-chloro-2-(2,3-dimethoxy phenoxy group)-the 4-dimethylamino phenyl]-N '-(thiazol-2-yl) urea (136mg, 61%) be from 5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(dimethylamino) aniline (161mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：450(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.61 (s, 3H), 2.66 (s, 3H), 3.70 (s, 3H), 3.89 (s, 3H), 6.58 (s, 1H), 6.68 (dd, J=8.4,1.2Hz, 1H), 6.92 (dd, J=8.4,1.6Hz, 1H), 7.04-7.10 (m, 2H), 8.44 (s, 1H), 9.20 (br, 1H), 10.26 (br, 1H).

Embodiment 79

N-[5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(4-morpholino base) phenyl]-N '-(thiazol-2-yl) urea

In the bottle of sealing, (0.35g 1.0mmol) heats 48h with morpholine (4mL) down at 100 ℃ with 4,5-, two chloro-2-(2,3-dimethoxy phenoxy group)-1-oil of mirbane.Reaction mixture is cooled to rt, is dissolved in ethyl acetate (15mL).With solution washing (water, salt solution), concentrate, obtain required oil of mirbane, according to common processes B, it is reduced to 5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(4-morpholino base) aniline (0.22g, 61%).N-[5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(4-morpholino base) phenyl]-N '-(thiazol-2-yl) urea (127mg, 52%) be from 5-chloro-2-(2,3-dimethoxy phenoxy group)-4-(4-morpholino base) aniline (182mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：492(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 2.83 (m, 4H), 3.69-3.72 (m, 7H), 3.89 (s, 3H), 6.58 (s, 1H), 6.69 (dd, J=8.4,1.6Hz, 1H), 6.93 (dd, J=8.4,1.6Hz, 1H), and 7.05-7.10 (m, 2H), 7.31 (d, J=3.2Hz, 1H), 8.48 (s, 1H), 9.02 (br, 1H), 10.25 (s, 1H).

Embodiment 80

N-[2-(2,4 difluorobenzene oxygen base) pyridin-3-yl]-N '-(thiazol-2-yl) urea

N-2-(2,4-two fluorophenoxies) pyridin-3-yl-N '-(thiazol-2-yl) urea (112mg, 65%) is from 3-amino-2-(2,4 difluorobenzene oxygen base) pyridine (111mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：350(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 7.08-7.16 (m, 3H), 7.20-7.26 (m, 1H), 7.36 (d, J=3.2Hz, 1H), 7.40-7.46 (m, 1H), 7.71 (dd, J=4.8,1.6Hz, 1H), 8.69 (dd, J=8.0,1.6Hz, 1H), 9.00 (br, 1H), 10.31 (br, 1H).

Embodiment 81

N-[2-(2-fluorophenoxy) pyridin-3-yl]-N '-[thiazol-2-yl] urea

N-2-(2-fluorophenoxy) pyridin-3-yl-N '-(thiazol-2-yl) urea (112mg, 68%) be from 3-amino-2-(2-fluorophenoxy) pyridine (102mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：332(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 7.09 (d, J=3.6Hz, 1H) 7.13 (dd, J=8.0,4.8Hz, 1H), 7.25-7.39 (m, 5H), 7.71 (dd, J=4.8,1.6Hz, 1H), 8.69 (dd, J=8.4,1.6Hz, 1H), 9.00 (br, 1H), 10.31 (br, 1H).

Embodiment 82

N-[2-(2-methoxyl group phenoxy group) pyridin-3-yl]-N '-(thiazol-2-yl) urea

2-(2-methoxyl group) phenoxy group-3-nitropyridine (0.86g, 70%) is that (0.68g, 5.5mmol) (1.05g 5.0mmol) prepares according to common processes A with 2-bromo-3-nitropyridine from the 2-methoxyphenol.According to common processes B, this compound is reduced to 2-(2-methoxyl group phenoxy group)-3-aminopyridine (0.49g, 65%).N-[2-(2-methoxyl group phenoxy group) pyridin-3-yl]-N '-(thiazol-2-yl) urea (126g, 74%) be from 2-(2-methoxyl group phenoxy group)-3-aminopyridine (108mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：344(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.69 (s, 3H), 6.74 (d, J=3.6Hz, 1H), 6.99-7.01 (m, 2H), 7.16-7.21 (m, 3H), 7.45 (d, J=2.8Hz, 1H), 7.71 (d, J=4.0Hz, 1H), 8.57-8.59 (d, J=8.0Hz, 1H), 8.89 (br, 1H), 10.44 (br, 1H).

Embodiment 83

N-[2-(2,3-dimethoxy phenoxy group) pyridin-3-yl]-N-(thiazol-2-yl) urea

2-(2,3-dimethoxy) phenoxy group-3-nitropyridine (1.03g, 75%) is that (0.85g, 5.5mmol) (1.05g 5.0mmol) prepares according to common processes A with 2-bromo-3-nitropyridine from 2,3-syringol.According to common processes B, this compound is reduced to 2-(2,3-dimethoxy phenoxy group)-3-aminopyridine (0.57g, 62%).N-[2-(2,3-dimethoxy phenoxy group) pyridin-3-yl]-N '-(thiazol-2-yl) urea (131mg, 70%) is from 2-(2,3-dimethoxy phenoxy group)-3-aminopyridine (123mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：374(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.58 (s, 3H), 3.87 (s, 3H), 6.81 (dd, J=1.6,8.0Hz, 1H), 6.95 (dd, J=1.6,8.4Hz, 1H), and 7.05-7.07 (m, 3H), 7.35 (d, J=3.2Hz, 1H), 7.67-7.79 (m, 1H), 8.64-8.86 (dd, J=2.4,8.0Hz, 1H), 8.89 (br, 1H), 10.26 (br, 1H).

Embodiment 84

N-[4-chloro-2-(2-chlorobenzene formacyl) phenyl]-N '-(thiazol-2-yl) urea

N-[4-chloro-2-(2-chlorobenzene formacyl) phenyl]-N '-(thiazol-2-yl) urea (0.51g, 86%) is from 2-amino-2 ', 5-two chloro benzophenones (0.4g, 1.50mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：394(M+1)， ¹H?NMR(400MHz，CDCl ₃)：δ6.45(br，1H)，6.79(dd，J＝1.2，7.6Hz，2H)，7.11(d，J＝7.2Hz，1H)，7.25-7.49(m，1H)，6.91-7.33(m，3H)，8.65(d，J＝8.8Hz，1H)，8.68(d，J＝9.6Hz，1H)，8.93(br，1H).

Embodiment 85

N-[4-chloro-2-(2-fluoro benzoyl) phenyl]-N '-(thiazol-2-yl) urea

N-[4-chloro-2-(2-fluoro benzoyl) phenyl]-N '-(thiazol-2-yl) urea (116mg, 62%) be from 2-amino-5-chloro-2 '-fluorine benzophenone (125mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：377(M+1) ⁺.

Embodiment 86

N-[2-(2,4 difluorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(2,4 difluorobenzene sulfenyl)-1-oil of mirbane (1.04g, 78%) is that (0.73g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from the 2,4 difluorobenzene thiophenol.According to common processes B, this compound is reduced to 2-(2,4 difluorobenzene sulfenyl) aniline (0.64g, 70%).1-[2-(2,4 difluorobenzene sulfenyl) phenyl]-3-(thiazol-2-yl) urea (130g, 72%) be from 2-(2,4 difluorobenzene sulfenyl) aniline (118mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：365(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.69-6.79 (m, 3H), 6.85 (d, J=3.6Hz, 1H), 7.04-7.09 (m, 1H), 7.36-7.40 (m 2H), 7.51-7.53 (dd, J=1.6,8.0Hz, 1H), 8.42 (d, J=8.0Hz, 1H), 8.88 (br, 1H), 10.2 (br, 1H).

Embodiment 87

1-[2-(2-fluorobenzene sulfenyl) phenyl]-3-(thiazol-2-yl) urea

2-(2-fluorobenzene sulfenyl) oil of mirbane (1.03g, 83%) is that (0.70g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from the 2-fluoro thiophenol.According to common processes B, this compound is reduced to 2-(2-fluorobenzene sulfenyl) aniline (0.65g, 72%).N-[2-(2-fluorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea (129mg, 75%) be from 2-(2-fluorobenzene sulfenyl) aniline (107mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：347(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.74-6.82 (m, 1H), 7.02-7.07 (m, 2H), 7.14-7.23 (m, 3H), 7.29 (d, J=3.6Hz, 1H), 7.51-7.58 (m, 1H), 7.60 (dd, J=1.2,7.6Hz, 1H), 8.43-8.46 (d, J=8.8Hz, 1H), 9.08 (br, 1H), 10.39 (br, 1H).

Embodiment 88

N-[2-(2-chloro-4-fluorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(2-chloro-4-fluorobenzene sulfenyl) oil of mirbane (1.13g, 80%) is that (0.89g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from 2-chloro-4-fluoro thiophenol.According to common processes B, this compound is reduced to 2-(2-chloro-4-fluorobenzene sulfenyl) aniline (0.76g, 75%).N-[2-(2-chloro-4-fluorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea (144mg, 76%) be from 2-(2-chloro-4-fluorobenzene sulfenyl) aniline (126mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：381(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 6.59-6.68 (m, 1H), 6.96-7.04 (m, 2H), 7.16-7.22 (m, 1H), 7.26 (d, J=4.0Hz, 1H), 7.32-7.38 (m, 1H), 7.50-7.61 (m, 2H), 8.47 (d, J=8.0Hz, 1H), 9.00 (br, 1H), 10.23 (br, 1H).

Embodiment 89

N-[2-(2,3-dichlorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(2,3-dichlorobenzene sulfenyl) oil of mirbane (1.25g, 84%) is that (0.97g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from 2,3-thiophenol dichlorobenzene.According to common processes B, this compound is reduced to 2-(2,4 dichloro benzene sulfenyl) aniline (0.81g, 72%).N-[2-(2,3-dichlorobenzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea (154mg, 78%) be from 2-(2,3-chlorobenzene sulfenyl) aniline (135mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：397(M+1) ⁺.

¹H?NMR(400MHz，CDCl ₃)：δ6.34-6.44(m，1H)，6.72-6.78(m，1H)，6.88-6.96(m，1H)，7.11-7.22(m，3H)，7.50-7.57(m，2H)，8.51-8.53(d，J＝6.0Hz，1H)，9.08(br，1H)，10.32(br，1H).

Embodiment 90

N-[2-(3,5-dimethyl benzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(3,5-dimethyl benzene sulfenyl) oil of mirbane (1.01g, 78%) is that (0.76g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from 3,5-thiophenol dimethyl benzene.According to common processes B, this compound is reduced to 2-(3,5-dimethyl benzene sulfenyl) aniline (0.64g, 72%).N-[2-(3,5-dimethyl benzene sulfenyl) phenyl]-N '-(thiazol-2-yl) urea (131mg, 74%) be from 2-(3,5-dimethyl benzene sulfenyl) aniline (115mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：357(M+1) ⁺.

¹H?NMR(400MHz，CDCl ₃)：δ2.09(s，6H)，6.54-6.86(m，4H)，7.04-7.10(m，1H)，7.27-7.34(m，1H)，7.41-7.46(m，1H)，7.48-7.56(bs，1H)，8.41(d，J＝8.4Hz，1H)，8.20(br，1H)，11.8(br，1H).

Embodiment 91

N-[2-(2-methoxycarbonyl thiophenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(2-methoxycarbonyl thiophenyl) oil of mirbane (1.15g, 80%) is that (0.92g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from the methylthiosalicylic acid ester.According to common processes B, this compound is reduced to 2-(2-methoxycarbonyl thiophenyl) aniline (0.75g, 73%).N-[2-(2-methoxycarbonyl thiophenyl) phenyl]-N '-(thiazol-2-yl) urea (142mg, 74%) be from 2-(2-methoxycarbonyl thiophenyl) aniline (130mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：387(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.88 (s, 3H), 6.62-6.82 (m, 2H), 7.02-7.24 (m, 4H), 7.44-7.50 (m, 1H), 7.55-7.64 (bs, 1H), 7.87 (d, J=6.4,1H), 8.42 (d, J=8.0Hz, 1H), 8.82 (br, 1H), 10.9 (br.1H).

Embodiment 92

N-[2-(2-anisole sulfenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(2-anisole sulfenyl) oil of mirbane (1.07g, 82%) is that (0.76g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from the 2-methoxybenzenethiol.According to common processes B, this compound is reduced to 2-(2-anisole sulfenyl) aniline (0.66g, 70%).N-[2-(2-anisole sulfenyl) phenyl]-N '-(thiazol-2-yl) urea (110mg, 62%) be from 2-(2-anisole sulfenyl) aniline (115mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：359(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.48 (s, 3H), 6.77-6.89 (m, 2H), 6.90-7.00 (m, 2H), 7.05-7.24 (m, 2H), 7.29 (d, J=3.6Hz, 1H), 7.38-7.42 (m, 1H), 7.55 (dd, J=1.6,8.0Hz, 1H), and 8.41-8.43 (d, J=8.4Hz, 1H), 8.89 (br, 1H), 10.22 (br, 1H).

Embodiment 93

N-[2-(2-pyridine sulfenyl) phenyl]-N '-(thiazol-2-yl) urea

2-(2-pyridine sulfenyl) oil of mirbane (0.70g, 60%) is that (0.61g, 5.5mmol) (0.71g 5.0mmol) prepares according to common processes A with the 2-fluoronitrobenzene from the 2-mercaptopyridine.According to common processes B, this compound is reduced to 2-(2-pyridine sulfenyl) aniline (0.37g, 62%).N-[2-(2-pyridine sulfenyl) phenyl]-N '-(thiazol-2-yl) urea (98mg, 60%) be from 2-(2-pyridine sulfenyl) aniline (101mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：330(M+1) ⁺.

¹H?NMR(400MHz，CDCl ₃)：δ6.78-6.80(d，J＝8.0Hz，1H)，6.96(d，J＝3.6Hz，1H)，7.03-7.07(m，1H)，7.13-7.18(m，1H)，7.23(d，J＝2.8Hz，1H)，7.51-7.57(m，2H)，7.64(d，J＝1.6，7.6Hz，1H)，8.35(d，J＝4.0Hz，1H)，8.45(d，J＝8.4Hz，1H)，8.13(br，1H)，10.44(br，1H).

Embodiment 94

N-(2-propoxy-phenyl)-N '-(thiazol-2-yl) urea

N-(2-propoxy-phenyl)-N '-(thiazol-2-yl) urea (97mg, 70%) be from 2-propoxy-aniline (76mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：279(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.07 (t, J=7.6Hz, 3H), 1.88 (m, 2H), 4.05 (q, J=7.6Hz), 6.90-7.01 (m, 3H), 7.05 (d, J=3.6Hz), 7.36 (d, J=3.6Hz), 8.30 (dd, J=7.6,1.6Hz, 1H), 8.80 (br, 1H), 10.24 (br, 1H).

Embodiment 95

N-(2-butoxy phenyl)-N '-(thiazol-2-yl) urea

N-(2-butoxy phenyl)-N '-(thiazol-2-yl) urea (94mg, 65%) be from the 2-butoxy aniline (82mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：293(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 0.98 (t, J=7.2Hz, 3H), 1.54 (m, 2H), 1.84 (quint, J=6.4Hz, 2H), 4.10 (t, J=6.4Hz, 2H), and 6.90-7.03 (m, 3H), 7.05 (d, J=3.6Hz, 1H), 7.25 (d, J=3.6Hz, 1H), 8.30 (dd, J=8.0,1.2Hz, 1H), 9.00 (br, 1H), 10.20 (br, 1H).

Embodiment 96

N-(2-(cyclopentyloxy phenyl)-N '-(thiazol-2-yl) urea

2-(cyclopentyloxy)-1-oil of mirbane (1.04g, 80%) is that (0.46mL, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from cyclopentanol.According to common processes B, it is reduced to 2-(cyclopentyloxy) aniline (0.30g, 68%, 2.5mmol scale).N-(2-cyclopentyloxy phenyl)-N '-(thiazol-2-yl) urea (212mg, 70%) be from 2-(cyclopentyloxy) aniline (177mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：305(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.60-2.05 (m, 8H), 4.94 (m, 1H), 6.90-7.05 (m, 4H), 7.35 (d, J=4.0Hz, 1H), 8.30 (d, J=8.8Hz, 1H), 10.20 (br, 2H).

Embodiment 97

N-(2-isopropyl phenyl)-N '-(thiazol-2-yl) urea

2-(isopropoxy)-1-oil of mirbane (317mg, 70%) is that (0.24mL, 3.0mmol) (0.36g 2.5mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from isopropyl alcohol.According to common processes B, it is reduced to 2-(isopropoxy) aniline (198mg, 75%).N-(2-isopropyl phenyl)-N '-thiazolyl urea (218mg, 60%) be from 2-(isopropoxy) aniline (198mg, 01.3mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：279(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.36 (d, J=6.4Hz, 6H), 4.71 (m, 1H), 6.90-7.07 (m, 4H), 7.36 (d, J=3.6Hz, 1H), 8.30 (d, J=8.0Hz, 1H), 10.22 (br, 2H)

Embodiment 98

N-[2-(2-methyl propoxy-) phenyl]-N '-(thiazol-2-yl) urea

2-(2-methyl propoxy-)-1-oil of mirbane (0.73g, 75%) is that (0.46mL, 5.0mmol) (0.71g 5.0mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from the 2-methylpropanol.According to common processes B, it is reduced to 2-(2-methyl propoxy-) aniline (0.29g, 70%, 2.5mmol scale).N-[2-(2-methyl propoxy-) phenyl]-N '-(thiazol-2-yl) urea (189mg, 65%) be from 2-(2-methyl propoxy-) aniline (165mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：293(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.09 (d, 6H), 2.13 (m, 1H), 3.86 (d, J=6.8Hz, 1H), 6.90-7.10 (m, 4H), 7.38 (d, J=3.6Hz, 1H), 8.29 (d, J=7.2Hz, 1H), 10.05 (br, 2H).

Embodiment 99

N-[2-(cyclopentyl methoxyl group) phenyl]-N '-(thiazol-2-yl) urea

2-(cyclopentyl methoxyl group)-1-oil of mirbane (443mg, 80%) is that (0.32mL, 3.0mmol) (0.36g 2.5mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from pentamethylene methyl alcohol.According to common processes B, it is reduced to 2-(cyclopentyl methoxyl group) aniline (268mg, 70%).N-[2-(cyclopentyl methoxyl group) phenyl]-N '-(thiazol-2-yl) urea (286mg, 60%) be from 2-(cyclopentyl methoxyl group) aniline (0.25g, 1.5mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：319(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 1.40 (m, 2H), 1.65 (m, 4H), 1.91 (m, 2H), 2.45 (m, 1H), 3.98 (d, J=7.6Hz, 1H), 6.88-7.06 (m, 4H), 7.35 (d, J=3.6Hz, 1H), 8.29 (d, J=7.6Hz, 1H), 10.14, (br, 2H).

Embodiment 100

N-[2-(3-pentyloxy) phenyl]-N '-(thiazol-2-yl) urea

2-(3-pentyloxy)-1-oil of mirbane (366mg, 70%) is that (0.27mL, 2.5mmol) (0.36g 2.5mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from the 3-amylalcohol.According to common processes B, it is reduced to 2-(3-pentyloxy) aniline (0.25g, 80%).N-[2-(3-pentyloxy) phenyl]-N '-(thiazol-2-yl) urea (0.26g, 57%) be from 2-(3-pentyloxy) aniline (0.25g, 1.5mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：307(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 0.92 (t, J=7.2Hz, 6H), 1.75 (m, 4H), 4.38 (m, 1H), 6.89-7.06 (m, 4H), 7.36 (d, J=3.6Hz, 1H), 8.32 (d, J=8.0Hz, 1H).

Embodiment 101

N-[2-(2-pentyloxy) phenyl]-N '-(thiazol-2-yl) urea

2-(2-pentyloxy)-1-oil of mirbane (387mg, 74%) is that (0.27mL, 2.5mmol) (0.36g 2.5mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from the 2-amylalcohol.According to common processes B, it is reduced to 2-(2-pentyloxy) aniline (0.26g, 79%).N-[2-(2-pentyloxy) phenyl]-N '-(thiazol-2-yl) urea (280mg, 62%) be from 2-(2-pentyloxy) aniline (0.25g, 1.5mmol) and thiazolamine (150mg is 1.5mmol) according to common processes D preparation.

LC-MS(m/z)：307(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 0.93 (t, J=7.2Hz, 3H), 1.32 (d, J=6.0Hz, 3H), 1.40-1.90 (m, 4H), 4.55 (m, 1H), 6.85-7.07 (m, 4H), 7.36 (d, J=3.6Hz, 1H), 8.31 (d, J=8.0Hz, 1H), 10.15 (br, 1H).

Embodiment 102

N-[2-(2-methoxy ethoxy) phenyl]-N '-(thiazol-2-yl) urea

2-(2-methoxy ethoxy)-1-oil of mirbane (0.25g, 64%) is that (0.16mL, 2.0mmol) (0.21mL 2.0mmol) prepares according to common processes G with 1-fluoro-2-oil of mirbane from 2-methyl cellosolve.According to common processes B, it is reduced to 2-(2-methoxy ethoxy) aniline (0.13g, 60%).N-[2-(2-methoxy ethoxy) phenyl]-N '-(thiazol-2-yl) urea (115mg, 55%) be from 2-(2-methoxy ethoxy) aniline (115mg, 0.7mmol) and thiazolamine (140mg is 1.4mmol) according to common processes D preparation.

LC-MS(m/z)：295(M+1) ⁺.

¹H NMR (400MHz, acetone-d ₆): δ 3.37 (s, 3H), 3.78 (t, J=4.8Hz, 2H), 4.25 (t, J=4.8Hz, 2H), 6.95-7.06 (m, 4H), 7.37 (d, J=3.6Hz, 1H), 8.29 (d, J=8.0Hz, 1H), 8.80 (br, 1H), 10.20 (br, 1H).

Embodiment 103 (common processes (H))

(2-[3-(2-benzyl phenyl) urea groups] thiazole-4-yl) acetic acid

With intermediate 2-benzyl phenyl isocyanic ester (0.26g, 1.2mmol) (common processes H2) is dissolved in DMF (5mL), add 2-amino-4-thiazolyl acetic acid (0.20g, 1.2mmol).At 20 ℃ after following 16 hours, add ethyl acetate (60mL), mixture water extraction (5 * 20mL).Desolventizing in a vacuum, remaining oil is purifying on Waters Deltprep 4000, obtains the 150mg title compound.

Preparation system: (gradient 20-90%CH ₃CN 40min., 20ml/min., Rt=35min solvent orange 2 A=water, solvent B=CH ₃CN, solvent C=0,5%TFA/ water).

¹H-NMR (DMSO-d ₆): δ 10.90 (broad peak, 1H); 8.45 (s, 1H); 7.80 (s, 1H); 7.20 (multimodal, 9H); 6.85 (s, 1H); 3.98 (s, 2H); 3.53 (s, 2H).

HPLC-MS (method A): m/z=368 (M+1); Rt=4.10min

¹H?NMR(CDCl ₃)：δ7.98(br?d，2H)，7.88-7.70(m，4H)，7.50(t，3H)，7.18(d，1H)，6.84(br?s，1H)，3.71(br?s，2H)，2.70(br?s，2H)，2.52(m，1H)，1.90-1.70(m，5H)，1.45-1.15(m，5H).

Embodiment 104 (common processes (H))

(2-[3-(2-benzoyl-4-chloro-phenyl-) urea groups] thiazole-4-yl) acetic acid

As embodiment 103 preparation title compounds, wherein use (5-chloro-2-isocyanide acyl phenyl) phenyl ketone (common processes H2) as the intermediate isocyanic ester.

¹H-NMR (DMSO-d ₆): selected data: δ 9.48 (broad peak, 1H); 8.12 (broad peak, 1H); (multimodal, 9H); 6.87 (s, 1H); 3.57 (s, 2H).

HPLC-MS (method A): m/z=415 (M+1); Rt=3.79min

Embodiment 105 (common processes (H))

(2-[3-(2-(2-methylphenoxy) phenyl) urea groups] thiazole-4-yl) acetic acid

As embodiment 103 preparation title compounds, wherein use 2-(2-methylphenoxy) phenyl isocyanate (common processes H2) as the intermediate isocyanic ester.

¹H-NMR (DMSO-d ₆): δ 11.09 (broad peak, 1H); 8.88 (broad peak, 1H); 8.25 (d, 1H); 7.37 (d, 1H); 7.22 (t, 1H); 7.11 (multimodal, 2H); 6.97 (t, 1H); 6.89 (d, 1H); 6.87 (s, 1H); 6.67 (d, 1H); 3.53 (s, 2H); 2.23 (s, 3H).

HPLC-MS (method A): m/z=384 (M+1); Rt=4.67min

Embodiment 106 (common processes (H))

(2-[3-(2-(4-methoxyl group phenoxy group)-5-(trifluoromethyl) phenyl) urea groups] thiazole-4-yl) acetic acid

As embodiment 103 preparation title compounds, wherein use 2-(4-methoxyl group phenoxy group)-5-(trifluoromethyl) phenyl isocyanate (common processes H2) as the intermediate isocyanic ester.

¹H-NMR (DMSO-d ₆): δ 12.32 (broad peak, 1H); 11.20 (broad peak, 1H); 9.30 (d, 1H); 8.62 (d, 1H); 7.32 (d, 1H); 7.17 (d, 2H); 7.05 (d, 2H); 6.90 (s, 1H); 6.83 (d, 1H); 3.78 (s, 3H); 3.53 (s, 2H).

Embodiment 107 (common processes (H))

2-[3-(2-Phenoxyphenyl) urea groups] and thiazole-4-yl } acetic acid

As embodiment 103 preparation title compounds, wherein use 2-Phenoxyphenyl isocyanic ester (common processes H2) as the intermediate isocyanic ester.

¹H NMR (CDCl ₃) selected data: δ 3.47 (2H, s), 6.78 (1H, s), 6.90 (1H, d), 6.97-7.08 (3H, m), 7.09-7.19 (2H, m), 7.38 (2H, t), 8.16 (1H, br s), HPLC-MS (method A): m/z=370 (M+1); Rt=3.50min.

Embodiment 108 (common processes (H))

2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carboxylic acid

H prepares title compound according to common processes.

¹H?NMR(DMSO)：δ12.76(br，1H)，11.21(br?1H)，9.23(s，1H)，8.06(dd，1H)，7.94(s，1H)，7.33(d，1H)，7.10-7.01(m，2H)，6.74(t，1H)，6.55(dd，1H)，3.80(s，3H).

HPLC-MS (method B): m/z=422 (M+1); Rt=3.90min.

Embodiment 109 (common processes (H))

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's ethyl ester

¹H?NMR(DMSO)：δ11.44(s，1H)，8.99(s?1H)，8.06(dd，1H)，7.99(s，1H)，7.09(t，1H)，6.94(d，1H)，6.80(t，1H)，6.72(dd，1H)，6.67(d，1H)，4.25(q，2H)，3.84(s，3H)，3.67(s，3H)，1,28(t，3H).

HPLC-MS (method B): m/z=462 (M+1); Rt=4.53min.

Embodiment 110 (common processes (H))

(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) the acetic acid ethyl ester

¹H?NMR(DMSO)：δ11.16(br，1H)，9,09(br?1H)，8.08(dd，1H)，7.09(t，1H)，6.94(d，1H)，6.92(s，1H)，6.78(t，1H)，6.70(dd，1H)，6.65(d，1H)，4.06(q，2H)，3.84(s，3H)，3.66(s，2H)，3.62(s，3H)，1,18(t，3H).

HPLC-MS (method B): m/z=476 (M+1); Rt=4.43min.

Embodiment 111 (common processes (H))

(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) acetic acid

¹H?NMR(DMSO)：δ12.27(br，1H)，11.06(br，1H)，9.22(br，1H)，8.06(dd，1H)，7.32(dd，1H)，7.08(d，1H)，7.03(t，1H)，6.90(s，1H)，6.75-6.70(m，2H)，6.53(dd，1H)，3.79(s，3H)，3.55(s，2H).

HPLC-MS (method B): m/z=436 (M+1); Rt=3.85min.

Embodiment 112 (common processes (H))

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid

¹H?NMR(DMSO)：δ12.77(br，1H)，11.33(s，1H)，9.06(s，1H)，8.07(dd，1H)，7.93(s，1H)，7.08(d，1H)，7.09(t，1H)，6.95(dd，1H)，6.80(t，1H)，6.73-6.63(m，2H)，3.84(s，3H)，3.66(s，3H).

HPLC-MS (method B): m/z=434 (M+1); Rt=3.92min.

Embodiment 113 (common processes (H))

(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) acetic acid

¹H?NMR(DMSO)：δ12.30(br，1H)，11.14(br，1H)，9,08(br1H)，8.08(dd，1H)，7.08(t，1H)，6.94(d，1H)，6.89(s，1H)，6.78(t，1H)，6.70(dd，1H)，6.66(dd，1H)，3.84(s，3H)，3.66(s，3H)，3.54(s，2H).

HPLC-MS (method B): m/z=448 (M+1); Rt=3.76min.

Embodiment 114 (common processes (H))

2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-4-methylthiazol-5-carboxylic acid ethyl ester

¹H?NMR(DMSO)：δ11.35(s，1H)，9,38(br?1H)，8.05(dd，1H)，7.32(dd，1H)，7.10-7.02(m，2H)，6.76(t，1H)，6.56(dd，1H)，4.24(q，2H)，3.79(s，3H)，2.52(s，3H)，1,29(t，3H).

HPLC-MS (method B): m/z=464 (M+1); Rt=4.91min.

Embodiment 115 (common processes (H))

2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-4-methylthiazol-5-carboxylic acid

¹H?NMR(DMSO)：δ12.79(br，1H)，11.29(br，1H)，9,38(br1H)，8.05(dd，1H)，7.32(dd，1H)，7.10-7.01(m，2H)，6.75(t，1H)，6.54(dd，1H)，3.79(s，3H)，2.51(s，2H).

HPLC-MS (method B): m/z=436 (M+1); Rt=4.19min.

Embodiment 116 (common processes (H1))

N-ethyl-2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) ethanamide

¹H?NMR(DMSO)：δ11.03(s，1H)，9.22(br?1H)，8.06(dd，1H)，7.89(t，1H)，7.32(dd，1H)，7.10-7.00(m，2H)，6.82(s，1H)，6.72(t，1H)，6.53(dd，1H)，3.79(s，3H)，3.39(s，2H)，3.07(q，2H)，1,01(t，3H).

HPLC-MS (method B): m/z=463 (M+1); Rt=4.06min.

Embodiment 117 (common processes (H1))

2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl)-N-(2-methoxyl group-ethyl) ethanamide

¹H?NMR(DMSO)：δ11.03(br，1H)，9.22(br?1H)，8.06(dd，1H)，7.99(t，1H)，7.32(dd，1H)，7.10-7.00(m，2H)，6.82(s，1H)，6.72(t，1H)，6.53(dd，1H)，3.79(s，3H)，3.43(s，2H)，3.34(t，2H)，3.24(s，3H)，3.23(t，2H).

HPLC-MS (method B): m/z=493 (M+1); Rt=4.01min.

Embodiment 118 (common processes (H1))

2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl)-N-(2-morpholine-4-base ethyl) ethanamide

¹H NMR (DMSO): selected data: δ 11.01 (br, 1H), 9.77 (br, 1H), 9.23 (br 1H), 8.19 (br, 1H), 8.06 (dd, 1H), 7.32 (dd, 1H), 7.10-7.00 (m, 2H), 6.88 (s, 1H), 6.72 (t, 1H), 6.53 (dd, 1H), 3.97 (m, 2H), 3.79 (s, 3H), 3.64 (m, 2H), 3.47 (s, 2H).

HPLC-MS (method B): m/z=548 (M+1); Rt=3.24min.

Embodiment 119 (common processes (H1))

[2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) kharophen] the acetic acid methyl ester

¹H NMR (DMSO): selected data δ 11.06 (br, 1H), 9.25 (br 1H), 8.34 (t, 1H), 8.06 (dd, 1H), 7.31 (dd, 1H), 7.10-7.00 (m, 2H), 6.88 (s, 1H), 6.73 (t, 1H), 6.53 (dd, 1H), 3.85 (d, 2H), 3.79 (s, 3H), 3.63 (s, 2H), 3.49 (s, 2H).

HPLC-MS (method B): m/z=507 (M+1); Rt=3.74min.

Embodiment 120 (common processes (H1))

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's (2-methoxy ethyl) acid amides

¹H NMR (DMSO): selected data δ 11.29 (s, 1H), 9.13 (s1H), 8.08 (dd, 1H), 7.78 (t, 1H), 7.73 (s, 1H), 7.09 (t, 1H), 6.95 (dd, 1H), 6.80 (t, 1H), 6.71 (dd, 1H), 6.67 (dd, 1H), 3.84 (s, 3H), 3.67 (s, 3H), 3.26 (s, 3H).

HPLC-MS (method B): m/z=491 (M+1); Rt=3.86min.

Embodiment 121 (common processes (H1))

[2-(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-yl) kharophen] acetic acid

¹H?NMR(DMSO)：δ12.54(br，1H)，11.06(br，1H)，9.23(br1H)，8.21(t，1H)，8.06(dd，1H)，7.31(dd，1H)，7.09-7.01(m，2H)，6.88(s，1H)，6.72(t，1H)，6.53(dd，1H)，3.79(s，3H)，3.76(s，2H)，3.49(s，2H).

HPLC-MS (method B): m/z=493 (M+1); Rt=3.47min.

Embodiment 122 (common processes (H))

2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carboxylic acid's buserelin

¹H?NMR(DMSO)：δ11.21(s，1H)，9.19(s?1H)，8.08(dd，1H)，7.89(t，1H)，7.69(s，1H)，7.10(t，1H)，6.95(dd，1H)，6.79(t，1H)，6.73-6.66(m，2H)，3.84(s，3H)，3.66(s，3H)，3.25(q，2H)，1.08(t，3H).

HPLC-MS (method B): m/z=461 (M+1); Rt=3.96min.

Trace analysis:

Calculated value: C, 55.09%; H, 4.88%; N, 111.88%.

Measured value: C, 55.18%; H, 4.67%; N, 12.21%.

Embodiment 123 (common processes (H1))

[(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carbonyl) amino] the acetic acid methyl ester

¹H?NMR(DMSO)：δ11.26(s，1H)，9.20(s?1H)，8.26(t，1H)，8.09(dd，1H)，7.77(s，1H)，7.10(t，1H)，6.95(dd，1H)，6.79(t，1H)，6.72-6.67(m，2H)，4.01(d，2H)，3.84(s，3H)，3.66(s，3H)，3.65(s，3H).

Embodiment 124 (common processes (H))

(5-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-[1,3,4] thiadiazoles-2-yl) the acetic acid ethyl ester

¹H?NMR(DMSO)：δ11.35(s，1H)，9.31(s?1H)，8.03(t，1H)，8.04(dd，1H)，7.31(dd，1H)，7.10-7.02(m，2H)，6.75(t，1H)，6.55(dd，1H)，4.19-4.14(m，4H)，3.80(s，3H)，1.23(t，3H).

HPLC-MS (method B): m/z=465 (M+1); Rt=4.14min.

Embodiment 125 (common processes (H1))

[(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-carbonyl) amino] acetic acid

¹H?NMR(DMSO)：δ12.67(br，1H)，11.36(s，1H)，9.24(s1H)，8.08(dd，1H)，7.78(s，1H)，7.10(t，1H)，6.95(dd，1H)，6.79(t，1H)，6.72-6.67(m，2H)，3.93(d，2H)，3.84(s，3H)，3.67(s，3H).

HPLC-MS (method B): m/z=491 (M+1); Rt=3.58min.

Embodiment 126 (common processes (H))

(5-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups }-[1,3,4] thiadiazoles-2-yl) acetic acid

¹H?NMR(DMSO)：δ12.96(br，1H)，11.33(br，1H)，9.31(s1H)，8.04(dd，1H)，7.33(dd，1H)，7.11-7.01(m，2H)，6.75(t，1H)，6.55(dd，1H)，4.10(s，2H)，3.80(s，3H).

HPLC-MS (method B): m/z=337 (M+1); Rt=3.47min.

Embodiment 127 (common processes (H))

5-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups }-[1,3,4] thiadiazoles-2-carboxylic acid ethyl ester

¹H?NMR(DMSO)：δ11.91(s，1H)，9.26(s?1H)，8.05(dd，1H)，7.10(t，1H)，6.95(dd，1H)，6.83(t，1H)，6.75-6.67(m，2H)，4.40(q，2H)，3.84(s，3H)，3.66(s，3H)，1.35(t，3H).

HPLC-MS (method B): m/z=463 (M+1); Rt=4.34min.

Embodiment 128 (common processes (H))

(5-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups }-[1,3,4] thiadiazoles-2-yl) the acetic acid ethyl ester

¹H?NMR(DMSO)：δ11.42(s，1H)，9.17(s?1H)，8.05(dd，1H)，7.09(t，1H)，6.95(dd，1H)，6.81(t，1H)，6.72(dd，1H)，6.67(dd，1H)，4.19-4.13(m，4H)，3.84(s，3H)，3.66(s，3H)，1.22(t，3H).

HPLC-MS (method B): m/z=477 (M+1); Rt=4.10min.

Embodiment 129 (common processes (H1))

3-[2-(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) kharophen] the propionic acid methyl ester

¹H?NMR(DMSO)：δ11.11(s，1H)，9.07(br?1H)，8.08(dd，1H)，7.98(t，1H)，7.08(d，1H)，6.94(dd，1H)，6.81(s，1H)，6.77(dd，1H)，6.70(dd，1H)，6.65(dd，1H)，3.84(s，3H)，3.66(s，3H)，3.58(s，3H)，3.39(s，2H)，3.27(q，2H)，2.46(t，2H).

HPLC-MS (method B): m/z=533 (M+1); Rt=3.71min.

Embodiment 130 (common processes (H1))

2-(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl)-N-(2-morpholine-4-base ethyl) ethanamide

¹H NMR (DMSO): selected data δ 11.11 (br, 1H), 9.08 (br 1H), 8.07 (dd, 1H), 7.09 (t, 1H), 6.94 (dd, 1H), 6.86 (s, 1H), 6.77 (t, 1H), 6.70 (dd, 1H), 6.66 (dd, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 3.43 (s, 2H), 3.03-2.99 (m, 4H), 1.74-1.71 (m, 4H).

HPLC-MS (method B): m/z=560 (M+1); Rt=2.75min.

Embodiment 131 (common processes (H1))

[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino] the acetic acid methyl ester

¹H?NMR(DMSO)：δ11.27(s，1H)，9.36(s?1H)，8.32(t，1H)，8.07(dd，1H)，7.79(s，1H)，7.33(dd，1H)，7.11-7.02(m，2H)，6.75(t，1H)，6.55(dd，1H)，4.03(d，2H)，3.80(s，3H)，3.66(s，3H).

HPLC-MS (method B): m/z=493 (M+1); Rt=3.91min.

Embodiment 132 (common processes (H1))

3-[2-(2-{3-[2-(2,3-dimethoxy phenoxy group)-5-fluorophenyl] urea groups } thiazole-4-yl) kharophen] propionic acid

¹H?NMR(DMSO)：δ12.21(br，1H)，11.09(br，1H)，9.06(br1H)，8.07(dd，1H)，7.98(t，1H)，7.09(t，1H)，6.94(dd，1H)，6.81(s，1H)，6.76(t，1H)，6.71(t，1H)，6.66(dd，1H)，3.84(s，3H)，3.66(s，3H)，3.39(s，2H)，3.24(q，2H)，2.38(t，2H).

Embodiment 133 (common processes (H1))

[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino] acetic acid

¹H?NMR(DMSO)：δ12.74(br，1H)，11.23(s，1H)，9.31(s1H)，8.17(t，1H)，8.07(dd，1H)，7.78(s，1H)，7.33(dd，1H)，7.11-7.01(m，2H)，6.75(t，1H)，6.54(dd，1H)，3.92(d，2H)，3.80(s，3H).

Embodiment 134 (common processes (H1))

(R) 3-[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino]-2-hydroxyl-propionic acid

¹H?NMR(DMSO)：δ12.62(br，1H)，11.32(s，1H)，9.23(s1H)，8.06(dd，1H)，7.79-7.76(m，2H)，7.33(dd，1H)，7.11-7.02(m，2H)，7.06(dd，1H)，6.75(t，1H)，6.54(dd，1H)，5.62(br，1H)，4.16(t，1H)，3.80(s，3H)，3.64-3.52(m，1H)，3.49-3.40(m，1H).

HPLC-MS (method B): m/z=509 (M+1); Rt=3.49min.

Embodiment 135 (common processes (H1))

2-[(2-{3-[5-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) phenyl] urea groups } thiazole-4-carbonyl) amino]-3-hydroxyl-propionic acid

¹H?NMR(DMSO)：δ12.88(br，1H)，11.42(s，1H)，9.17(s1H)，8.06(dd，1H)，7.92(d，1H)，7.80(s，1H)，7.32(dd，1H)，7.11-7.01(m，2H)，6.75(t，1H)，6.54(dd，1H)，5.10(br，1H)，4.46-4.43(m，1H)，3.89(m，4H).

Embodiment 136

1-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-3-thiazol-2-yl-urea

2-pentamethylene carbonyl-4-monomethylaniline (10.2g) is that (10.7g, 0.1mol) (9.5g 0.1mol) prepares according to common processes I with the pentamethylene formonitrile HCN from right-Tolylamine.1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (132mg) be from 2-pentamethylene carbonyl-4-monomethylaniline (102mg, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：330(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.69(m，2H)，1.91(m，2H)，2.37(s，3H)，3.76(m，1H)，6.89(d，1H)，7.35(d，1H)，7.71(s，2H)，8.42(d，1H)，11.57(br，1H)ppm.

Embodiment 137

1-(2-isobutyryl-4-aminomethyl phenyl)-3-thiazol-2-yl-urea

2-sec.-propyl carbonyl-4-monomethylaniline (7.0g) be from right-Tolylamine (10.7g, 0.1mol) and isopropyl cyanide (6.9g is 0.1mol) according to common processes I preparation.1-(2-isobutyryl-4-aminomethyl phenyl)-3-thiazol-2-yl-urea (113mg) be from 2-sec.-propyl carbonyl-4-monomethylaniline (8 8mg, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：304(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.97(d，6H)，2.37(s，3H)，3.72(m，1H)，6.90(d，1H)，7.36(d，1H)，7.69(s，2H)，8.44(s，1H)，11.51(br，1H)，11.72(br，1H)ppm.

Embodiment 138

1-[5-fluoro-2-(3-methylbutyryl base) phenyl]-3-thiazol-2-yl-urea

The 2-[(2-methyl)-the propyl group carbonyl]-5-fluoroaniline (6.82g) be from-fluoroaniline (11.1g, 0.1mol) and the 3-methylbutyronitrile (8.3g is 0.1mol) according to common processes I preparation.1-[5-fluoro-2-(3-methyl-butyryl radicals)-phenyl]-3-thiazol-2-yl-urea (128mg) is from the 2-[(2-methyl)-the propyl group carbonyl]-the 5-fluoroaniline (97mg, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：322(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ0.99(d，6H)，2.23(m，1H)，2.83(d，2H)，6.75(m，1H)，6.93(d，1H)，7.62(d，1H)，7.92(dd，1H)，8.43(dd，1H)，11.60(br，1H)，12.04(br，1H)ppm.

Embodiment 139

1-[5-methyl-2-(3-methylbutyryl base) phenyl]-3-thiazol-2-yl-urea

2-[2-methyl-propyl carbonyl]-5-monomethylaniline (6.8g) be from-Tolylamine (10.2g, 0.1mol) and isopropyl cyanide (8.3g is 0.1mol) according to common processes I preparation.1-[5-methyl-2-(3-methylbutyryl base) phenyl]-3-thiazol-2-yl-urea (114mg) is from 2-[2-methyl-propyl carbonyl]-the 5-monomethylaniline (95mg, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：318(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ0.98(d，6H)，2.31(m，1H)，2.37(s，3H)，2.44(d，2H)，6.91(m，1H)，7.27(m，1H)，7.51(d，1H)，7.68(dd，1H)，8.45(d，1H)，11.58(br，1H)，11.60(br，1H)ppm.

Embodiment 140

[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid ethyl ester

(4-amino-3-pentamethylene carbonyl phenyl) acetic acid ethyl ester (2.7g) is that (18.0g, 0.1mol) (9.5g 0.1mol) prepares according to common processes I with the pentamethylene formonitrile HCN from (4-aminophenyl) acetic acid ethyl ester.[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid ethyl ester (140mg) is from (4-amino-3-pentamethylene carbonyl phenyl) acetic acid ethyl ester (138mg, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：402(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.12(t，3H)，1.73(m，2H)，1.82(m，2H)，3.27(m，1H)，3.62(s，2H)，4.15(q，2H)，6.89(d，1H)，7.44(dd，1H)，7.62(d，1H)，7.86(s，1H)，8.51(s，1H)，11.62(br，1H)ppm.

Embodiment 141

[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid

[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid (168mg) is that (201mg 0.5mmol) prepares according to common processes J from [3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid ethyl ester.

LC-MS(m/z)：374(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.66(m，2H)，1.96(m，2H)，3.71(s，2H)，3.92(m，1H)，7.05(d，1H)，7.38(d，1H)，7.56(dd，1H)，8.08(s，1H)，8.55(s，1H)，11.26(br，1H)ppm.

Embodiment 142

2-[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl]-the N-methylacetamide

2-[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-N-methylacetamide (154mg) is from [3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups) phenyl] acetic acid (186mg, 0.5mmol) and the THF solution of 1M methylamine (0.5mL is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：387(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃/DMSO-d ₆)：δ1.51(m，2H)，1.73(m，2H)，2.58(s，3H)，3.36(s，2H)，3.59(m，1H)，6.67(m，1H)，7.21(m，2H)，7.71(s，1H)，8.26(bs，1H)，10.95(br，1H)ppm.

Embodiment 143

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (154mg) is from (2-amino-5-aminomethyl phenyl) (cyclopentyl) ketone (102mg, 0.5mmol) and ethyl 2-amino-4-thiazolyl acetate (93mg is 0.5mmol) according to common processes D preparation.

LC-MS(m/z)：416(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.23(t，3H)，1.67(m，2H)，1.87(m，2H)，2.34(s，3H)，3.70(s，2H)，4.18(m，3H)，6.68(s，1H)，7.25(s，2H)，7.32(d，1H)，7.67(s，1H)，8.45(s，1H)，9.75(br，1H)，11.51(br，1H)ppm.

Embodiment 144

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } acetic acid

{ 2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-acetic acid (198mg) is that (208mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS(m/z)：388(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.73(m，2H)，1.86(m，2H)，2.32(s，3H)，3.55(s，2H)，3.86(m?1H)，6.84(s，1H)，7.36(d，1H)，7.84(d，1H)，8.15(d，1H)，10.62(br，1H)，11.92(br，1H)，12.24(br，1H)ppm.

Embodiment 145

{ 3-pentamethylene carbonyl-4-{3-(4-ethoxycarbonylmethyl group thiazol-2-yl)-urea groups } phenyl } the acetic acid ethyl ester

{ 3-pentamethylene carbonyl-4-{3-(4-ethoxycarbonylmethyl group-thiazol-2-yl)-urea groups }-phenyl }-acetic acid ethyl ester (205mg) is from (4-amino-3-pentamethylene carbonyl-phenyl) acetic acid ethyl ester (138mg, 0.5mmol) and ethyl 2-amino-4-thiazolyl acetate (93mg is 0.5mmol) according to common processes D preparation.

LC-MS(m/z)：488(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.24(t，6H)，1.67(m，2H)，1.88(m，2H)，2.34(s，3H)，3.61(s，2H)，3.71(s，2H)，3.73(m，1H)，4.17(m，4H)，4.18(m，3H)，6.69(s，1H)，7.42(d，2H)，7.85(s，1H)，8.53(s，1H)，11.64(br，1H)ppm.

Embodiment 146

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea (149mg) is from 2-pentamethylene carbonyl-4-monomethylaniline (102mg; 0.5mmol) and 5-methylsulfonyl-thiazol-2-yl-amine (106mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：408(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.65-1.77(m，4H)，1.88-1.97(m，4H)，2.40(s，3H)，3.21(s，3H)，3.81(p，1H)，7.41(dd，1H)，7.78(s，1H)，8.31(d，1H)，8.43(d，1H)，11.57(br，1H)，11.95(br，1H)ppm.

Embodiment 147

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxylic acid's ethyl ester

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxylic acid's ethyl ester (3.6g) is from 2-pentamethylene carbonyl-4-monomethylaniline (2.04g, 10mmol) (1.72g 10mmol) prepares according to common processes D with ethyl 2-amino-4-thiazolyl acetic acid ester.

LC-MS(m/z)：402(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.35(t，3H)，1.62-1.78(m，4H)，1.83-1.96(m，4H)，2.37(s，3H)，3.74(p，1H)，4.33(q，2H)，7.36(d，1H)，7.72(s，1H)，7.81(s，1H)，8.44(d，1H)，9.25(br，1H)，11.84(br，1H)ppm.

Embodiment 148

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxylic acid (3.2g) is from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(3.6g 8.95mmol) prepares according to common processes J thiazole-4-carboxylic acid's ethyl ester.

LC-MS(m/z)：374(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.58(m，4H)，1.73(m，4H)，2.29(s，3H)，3.72(m，1H)，7.13(s，1H)，7.28(d，1H)，7.63(d，1H)，7.72(br，1H)，7.94(s，1H)，8.22(br，1H)，10.92(br，1H)ppm.

Embodiment 149

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxamide

2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-carboxamide (145mg) is from 2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-(187mg 0.5mmol) prepares according to common processes K the thiazole-4-carboxylic acid.

LC-MS(m/z)：373(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.61(m，4H)，1.73(m，2H)，1.88(m，2H)，2.32(s，3H)，3.86(m，1H)，7.38(d，1H)，7.56(s，1H)，7.68(s，1H)，7.84(s，1H)，7.93(s，1H)，8.14(d，1H)，10.73(br，1H)，11.86(br，1H)ppm.

Embodiment 150

2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-ethanamide

2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-ethanamide (325mg) is from 2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-(386mg 1.0mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS(m/z)：387(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.60(m，4H)，1.73(m，2H)，1.87(m，2H)，2.31(s，3H)，3.38(s，2H)，3.88(m，1H)，6.77(s，1H)，6.97(s，1H)，7.38(d，2H)，7.83(s，1H)，8.15(d，1H)，10.63(br，1H)，11.81(br，1H)ppm.

Embodiment 151

2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide

2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide (346mg) is from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(386mg 1.0mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS(m/z)：401(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.70(m，4H)，1.88(m，2H)，1.94(m，2H)，2.63(s，3H)，2.79(d，3H)，3.62(s，2H)，3.77(p，1H)，6.65(s，1H)，6.77(br，1H)，7.35(dd，1H)，7.71(s，1H)，8.43(d，1H)，9.15(br，1H)，11.70(br，1H)ppm.

Embodiment 152

4-(2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl }-ethanoyl)-1-methyl-piperazine _ chlorine

4-(2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl-ethanoyl)-1-methyl-piperazine (337mg) is from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-guanidine-acetic acid (386mg, 1.0mmol) and N methyl piperazine according to common processes K preparation.

4-(2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl-ethanoyl)-1-methyl-piperazine _ chlorine (392mg) be from 4-(2-{2-[3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea groups]-thiazole-4-yl-ethanoyl)-1-methyl-piperazine (386mg; 1.0mmol) handle, prepare succeeded by collecting solid product with anhydrous hydrogen chloride (5mL, the 4.0M solution in two _ alkane).

LC-MS(m/z)：471(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.60(m，4H)，1.72(m，2H)，1.87(m，2H)，2.32(s，3H)，2.47(s，3H)，2.76(d，2H)，2.94(m，2H)，3.37(m，2H)，3.73(d，2H)，3.84(m，2H)，4.22(d，1H)，?4.44(d，1H)，6.83(s，1H)，7.36(d，1H)，7.82(s，1H)，8.11(d，1H)，10.63(br，1H)，10.82(br，1H)ppm.

Embodiment 153

1-[4-methyl-2-(2-methyl propoxy-) phenyl]-3-thiazol-2-yl-urea

3-(2-methyl propoxy-)-4-nitrotoluene (0.78g) is that (0.46mL, 5.0mmol) (0.77g 5.0mmol) prepares according to common processes G with 3-fluoro-4-nitrotoluene from the 2-methylpropanol.According to common processes C, with its reduction, obtain 4-methyl-2-(2-methyl propoxy-) aniline (0.47g).N-[4-methyl-2-(2-methyl propoxy-) phenyl]-N '-(thiazol-2-yl) urea (210mg) be from 4-methyl-2-(2-methyl propoxy-) aniline (179mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：306(M+1) ⁺

¹H?NMR(400MHz，CDCl ₃)：δ1.01(d，6H)，2.16(m，1H)，2.32(s，3H)，3.78(d，2H)，6.70(s，1H)，6.75(d，1H)，6.86(d，1H)，7.40(d，1H)，8.07(d，1H)，9.30(br，1H)，10.72(br，1H)ppm.

Embodiment 154

2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (485mg) is from 4-methyl-2-(2-methyl propoxy-) aniline (360mg, 2.0mmol) and ethyl 2-amino-4-thiazolyl acetate (372mg is 2.0mmol) according to common processes D preparation.According to this ester of common processes J hydrolysis, obtain 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid (400mg).

LC-MS(m/z)：464(M+1?) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.01(d，6H)，2.07(m，1H)，2.23(s，3H)，3.53(s，2H)，3.77(d，2H)，6.67(d，1H)，6.81(s，2H)，7.91(d，1H)，8.01(br，1H)，11.45(br，1H)，12.35(br，1H)ppm.

Embodiment 155

2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide

{ 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide (150mg) is that (182mg is 0.5mmol) according to common processes K preparation from { 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid.

LC-MS(m/z)：477(M+1) ⁺

¹H?NMR(400MHz，DMSO-d ₆)：δ1.00(d，6H)，2.06(m，1H)，2.19(s，3H)，2.48(s，3H)，3.40(s，2H)，3.68(d，2H)，6.54(s，1H)，6.59(d，2H)，7.40(br，1H)，7.91(d，1H)，8.08(br，1H)，11.27(br，1H)ppm.

Embodiment 157

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-methyl-thiazol-2-yl)-urea (66mg, 77%) is that (51mg 0.25mmol) prepares according to common processes D from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone.

LC-MS (m/z): 344 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.60-175 (m, 4H), 1.80-194 (m, 4H), 2.32 (s, 3H), 2.36 (s, 3H), 3.73 (p, 1H), 6.44 (s, 1H), 7.28 (d, 1H), 7.35 (d, 1H), 7.67 (s, 1H), 8.44 (br, 1H) and 11.66 (br, 1H).

Embodiment 158

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-methoxymethyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-methoxymethyl-thiazol-2-yl)-urea (64mg, 69%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (50mg, 0.25mmol) and 4-methoxymethyl-thiazol-2-yl amine (54mg, 0.375mmol) according to common processes D preparation, obtain title compound.

LC-MS (m/z): 373 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.70 (m, 4H), 1.88 (m, 4H), 2.36 (s, 3H), 3.41 (s, 2H), 3.72 (m, 1H), 4.44 (s, 3H), 6.78 (dd, 1H), 7.32 (d, 1H), 7.70 (s, 1H), 8.42 (d, 1H), 10.52 (br, 1H) and 11.64 (br, 1H).

Embodiment 159

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea

Under 0 ℃, to 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-hydroxymethyl-thiazol-2-yl]-urea (1.8g, CH 5mmol) ₂Cl ₂(40mL) solution add Et3N (2.88mL, 20mmol), dimethyl sulfoxide (DMSO) (10mL) is succeeded by sulphur trioxide-pyridine (2.38g, 15.0mmo l).Reaction mixture is stirred 1h, pour into then in the water (30mL).Mixture CH ₂Cl ₂Extraction, with organic layer with 1.0N ammonium chloride (2 * 20mL), water (2 * 20mL), salt solution (1 * 20mL) washing, dry (Na ₂SO ₄), concentrate, obtain solid.(silicon-dioxide, hexane/EtOAc 20-50%), obtain 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (1.59g, 86%) to this solid, are white solid through the column chromatography purifying.

LC-MS (m/z): 358 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.64 (m, 4H), 1.74 (m, 2H), 1.90 (m, 2H), 2.35 (s, 3H), 3.89 (p, 1H), 7.41 (d, 1H), 7.88 (s, 1H), 8.17 (d, 1H), 8.24 (s, 1H), 9.76 (s, 1H), 10.75 (s, 1H) and 12.20 (br, 1H).

Embodiment 160

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-hydroxymethyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-hydroxymethyl-thiazol-2-yl)-urea (2.66g, 92%) be from acetic acid 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl ester (3.2g, 8.0mmol) according to common processes J preparation, obtain title compound.

LC-MS (m/z): 360 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.75 (m, 4H), 1.89 (m, 4H), 2.34 (s, 3H), 3.88 (m, 1H), 4.43 (d, 2H), 5.20 (t, 1H), 6.82 (s, 1H), 7.39 (d, 1H), 7.85 (s, 1H), 8.18 (d, 1H), 10.66 (br, 1H) and 11.72 (br, 1H).

Embodiment 161

1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (2.16g, 57.1%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (2.03g, 10.0mmol) and 4-chloromethyl-thiazol-2-yl amine (1.72g is 10.0mmol) according to common processes D preparation.

LC-MS (m/z): 378 (M+1) ⁺, ¹H NMR (400MHz, CDCl ₃): δ 1.68 (m, 4H), 1.88 (m, 4H), 2.36 (s, 3H), 3.76 (m, 1H), 4.52 (s, 2H), 6.88 (s, 1H), 7.34 (d, 1H), 7.73 (s, 1H), 8.42 (d, 1H), 11.36 (br, 1H) and 11.75 (br, 1H).

Embodiment 162

1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

(7.6g, methyl alcohol 100mmol) (150mL) solution add 1,3-Dichloro acetone, and (12.7g 100mmol), stirs reaction mixture 3-4 hour under rt to thiocarbamide.Enriched mixture obtains crude product in a vacuum, is hydrochloride.Then with this salt Et ₂The O washing (3 * 200mL), concentrate in a vacuum, obtain 4-chloromethyl-thiazol-2-yl amine, yield 95-100%.

(7.45g, 50.0mmol) at two _ alkane: the solution in the water mixture (8: 2) adds sodiumazide, and (4.87g 75.0mmo1), makes reaction mixture refluxed 2-3h to 4-chloromethyl-thiazol-2-yl amine.Enriched mixture to remove whole two _ alkane, is dissolved in EtOAc (200mL) with resistates in a vacuum.With the organic layer water (2 * 200mL), salt solution (2 * 200mL) washing, through Na ₂SO ₄Drying concentrates in a vacuum, obtains 4-azido methyl-thiazol-2-yl amine, yield 70-90%.

Make 4-azido methyl-thiazol-2-yl amine carry out the generation of urea according to common processes D, obtain required urea (1-(4-azido methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea), yield 65-85%.

To 1-(4-azido methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (7.7g, EtOH 20mmol) (100mL) solution adds the palladium on carbon (200mg) of catalytic amount, make reaction mixture hydrogenation (1atms) 3-4 hour, obtain 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.This crude product passes through the flash column chromatography purifying then, uses DCM: EtOAc (80: 20 to 50: 50) obtains required amine (5.7g, 80%) as eluent.

LC-MS (m/z): 359 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.48 (m, 2H), 1.64 (m, 4H), 1.82 (m, 2H), 2.30 (s, 3H), 3.46 (d, 2H), 3.54 (p, 1H), 3.76 (t, 2H), 6.84 (s, 1H), 7.07 (s, 1H), 7.76 (d, 1H), 8.32 (d, 1H), 9.64 (br, 1H) and 11.18 (br, 1H).

Embodiment 163

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-dimethylamino methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-dimethylamino methyl-thiazol-2-yl)-urea (79mg; 82%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and (30mg; 0.3mmol) and dimethyl amine (0.1mL; 2.0M solution among the THF) according to common processes O preparation, obtain title compound.

LC-MS (m/z): 387 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.62-1.72 (m, 4H), 1.78-1.88 (m, 4H), 2.23 (s, 6H), 2.34 (s, 3H), 3.53 (s, 2H), 3.70 (p, 1H), 6.64 (s, 1H), 7.30 (d, 1H), 7.64 (s, 1H), 8.32 (d, 1H), 10.25 (br, 1H) and 11.35 (br, 1H).

Embodiment 164

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-ethanamide

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-ethanamide (88mg, 88%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) and Acetyl Chloride 98Min. (0.02mL is 0.25mmol) according to common processes T preparation.

LC-MS (m/z): 401 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.56 (m, 4H), 1.72 (m, 2H), 1.78 (m, 2H), 2.22 (s, 3H), 2.82 (s, 3H), 3.18 (t, 1H), 3.64 (m, 1H), 4.07 (s, 2H), 6.55 (s, 1H), 7.22 (d, 1H), 7.53 (s, 1H), 8.18 (d, 1H), 10.18 (br, 1H) and 11.58 (br, 1H).

Embodiment 165

1-{4-[2-(tertiary butyl-dimethyl-silicon alkoxyl group)-ethyl]-thiazol-2-yl }-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-{4-[2-(tertiary butyl-dimethyl-silicon alkoxyl group)-ethyl]-thiazol-2-yl }-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (425mg, 87%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (203mg, 1.00mmol) and 4-[2-(tertiary butyl-dimethyl-silicon alkoxyl group)-ethyl]-(310mg 1.20mmol) prepares according to common processes D thiazol-2-yl amine.

LC-MS(m/z)：488(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ0.10(s，9H)，0.85(s，6H)，1.70-1.78(m，4H)，1.82-194(m，4H)，2.35(s，3H)，2.84(t，2H)，3.73(p，1H)，3.87(t，2H)，6.52(s，1H)，6.60(d，1H)，7.32(d，1H)，7.72(s，1H)，8.48(br，1H)，11.68(br，1H).

Embodiment 166

Acetic acid 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl ester

Acetic acid 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl ester (3.66g, 91%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (2.03g, 10.0mmol) and acetic acid 2-amino-thiazolyl--4-ylmethyl ester (2.05g is 12.0mmol) according to common processes D preparation.

LC-MS (m/z): 402 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.70 (m, 4H), 1.86 (m, 4H), 2.10 (s, 3H), 2.37 (s, 3H), 3.75 (m, 1H), 5.09 (s, 2H), 6.87 (s, 1H), 7.35 (d, 1H), 7.71 (s, 1H), 8.45 (d, 1H), 9.20 (br, 1H) and 11.75 (br, 1H).

Embodiment 167

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-1-methyl-3-thiazol-2-yl-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-1-methyl-3-thiazol-2-yl-urea (287mg, 83%) is that (217mg 1.00mmol) prepares according to common processes D from cyclopentyl-(5-methyl-2-methylamino-phenyl)-ketone.

LC-MS (m/z): 344 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.72 (m, 4H), 1.88 (m, 4H), 2.37 (s, 3H), 3.42 (s, 3H), 3.84 (p, 1H), 6.85 (d, 1H), 6.94 (d, 1H), 7.17 (d, 1H), 7.43 (d, 1H), 7.46 (s, 1H) and 9.62 (br, 1H).

Embodiment 168

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (109mg, 60%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg, 0.5mmol) and 5-chloro-thiazol-2-yl amine (0.06mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：364(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.72(m，4H)，1.93(m，4H)，2.38(s，3H)，3.80(m，1H)，7.37(d，1H)，7.64(s，1H)，7.74(s，1H)，8.44(d，1H)，11.69(br，1H).

Embodiment 169

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (127mg, 62%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg, 0.5mmol) and 5-bromo-thiazol-2-yl amine (108mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：409(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.72(m，4H)，1.93(m，4H)，2.38(s，3H)，3.78(m，1H)，7.38(d，1H)，7.66(s，1H)，7.74(s，1H)，8.44(d，1H)，11.67(br，1H).

Embodiment 170

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-5-fluoro-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-5-fluoro-phenyl)-urea (132mg, 64%) be from (2-amino-4-fluoro-phenyl)-cyclopentyl-ketone (104mg, 0.5mmol) and 5-bromo-thiazol-2-yl amine (108mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：413(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.72(m，4H)，1.93(m，4H)，2.38(s，3H)，3.74(m，1H)，6.81(m，1H)，7.61(s，1H)，8.01(dd，1H)，8.42(dd，1H)，11.02(br，1H)，12.16(br，1H).

Embodiment 171

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-4-methyl-thiazole-5-carboxylic acid ethyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-4-methyl-thiazole-5-carboxylic acid ethyl ester (154mg, 80%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg, 0.5mmol) and 2-amino-4-methyl-thiazole-5-carboxylic acid ethyl ester (112mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：416(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.33(t，3H)，1.66(m，4H)，1.87(m，4H)，2.37(s，3H)，2.59(s，3H)，3.72(m，1H)，4.28(q，2H)，7.37(s，1H)，7.70(s，1H)，8.48(s，1H)，10.35(br，1H)，11.81(br，1H).

Embodiment 172

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-4-methyl-thiazole-5-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-4-methyl-thiazole-5-carboxylic acid (198mg, 95%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(208mg 0.5mmol) prepares according to common processes J 4-methyl-thiazole-5-carboxylic acid ethyl ester.

LC-MS(m/z)：388(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.66(m，4H)，1.74(m，2H)，1.94(m，2H)，2.61(s，3H)，2.65(s，3H)，3.88(m，1H)，7.42(d，1H)，7.88(s，1H)，8.20(d，1H)，10.25(br，1H)，12.22(br，2H).

Embodiment 173

1-(2 '-amino-[4,4 '] connection thiazolyl-2-yl)-3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea

1-(2 '-amino-[4,4 '] connection thiazolyl-2-yl)-3-(2-pentamethylene carbonyl-4-aminomethyl phenyl)-urea (85mg, 79%) is that (51mg 0.25mmol) prepares according to common processes D from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone.

LC-MS (m/z): 428 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.25 (m, 4H), 1.73 (m, 4H), 2.37 (s, 3H), 3.77 (p, 1H), 5.24 (br, 2H), 6.99 (s, 1H), 7.02 (s, 1H), 7.53 (dd, 1H), 7.58 (s, 1H), 7.72 (s, 1H), 8.42 (br, 1H) and 11.78 (br, 1H).

Embodiment 174

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-methoxyl group-N-methyl-ethanamide

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-methoxyl group-N-methyl-ethanamide (88mg, 82.%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 431 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.72 (m, 4H), 1.93 (m, 4H), 2.35 (s, 3H), 2.80 (s, 2H), 3.70 (s, 3H), 3.85 (s, 3H), 4.21 (p, 1H), 6.67 (s, 1H), 6.91 (d, 1H), 7.54 (dd, 1H), 7.70 (d, 1H), 8.40 (br, 1H) and 11.52 (br, 1H).

Embodiment 175

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-morpholine-4-base-2-oxo-ethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-morpholine-4-base-2-oxo-ethyl)-thiazol-2-yl]-urea (92mg, 80%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 457 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.64 (m, 4H), 1.82 (m, 2H), 1.88 (m, 2H), 2.34 (s, 3H), 2.96-3.14 (dd, 2H), 3.49 (t (2H), 3.60 (m, 4H), 3.72 (p, 1H), 3.76 (s, 2H), 6.60 (s, 1H), 7.33 (d, 1H), 7.67 (s, 1H), 8.42 (d, 1H), 8.70 (br, 1H) and 11.28 (br, 1H).

Embodiment 176

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(4-methyl-piperazine-1-yl)-ethanamide

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(4-methyl-piperazine-1-yl)-ethanamide (105mg, 87%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 485 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.66 (m, 4H), 1.82 (m, 2H), 1.94 (m, 2H), 2.35 (s, 3H), 3.02 (m, 2H), 3.46 (s, 3H), 3.53 (t (2H), 3.64 (m, 4H), 3.76 (p, 1H), 3.80 (s, 2H), 5.36 (br, 1H), 6.56 (s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.46 (d, 1H), 8.82 (br, 1H) and 11.46 (br, 1H).

Embodiment 177

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(2-morpholine-4-base-ethyl)-ethanamide

2-{2-[3-{2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(2-morpholine-4-base-ethyl)-ethanamide (108mg, 86%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.2mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 500 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.22 (t, 2H), 1.35 (t, 4H), 1.70 (m, 2H), 1.86 (m, 2H), 1.94 (m, 2H), 2.32 (s, 3H), 2.88 (s, 2H), 2.96 (m, 4H), 3.22 (t, 4H), 3.77 (p, 1H), 5.30 (br, 1H), 6.58 (s, 1H), 7.34 (d, 1H), 7.90 (s, 1H), 8.38 (d, 1H), 9.14 (br, 1H) and 11.32 (br, 1H).

Embodiment 178

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-carboxylic acid's methyl nitrosourea

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-carboxylic acid's methyl nitrosourea (77mg, 80%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 387 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.74 (m, 4H), 1.82 (m, 2H), 1.94 (m, 2H), 2.38 (s, 3H), 3.00 (d, 3H), 3.13 (m, 1H), 3.78 (p, 1H), 6.94 (s, 1H), 7.34 (d, 1H), 7.51 (br, 1H), 7.72 (d, 1H), 8.40 (d, 1H) and 11.88 (br, 1H).

Embodiment 179

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea (92mg, 80%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 443 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.70 (m, 4H), 1.90 (m, 4H), 2.36 (s, 3H), 3.12 (m, 2H), 3.76 (m, 4H), 3.82 (m, 1H), 6.69 (s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.38 (d, 1H), 9.83 (br, 1H) and 11.86 (br, 1H).

Embodiment 180

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethanoyl)-Toluidrin

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethanoyl)-Toluidrin (88mg; 76%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 465 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.72 (m, 4H), 1.92 (m, 4H), 2.37 (s, 3H), 3.13 (s, 3H), 3.30 (s, 2H), 3.81 (p, 1H), 4.88 (br, 1H), 6.66 (s, 1H), 7.36 (d, 1H), 7.72 (d, 1H), 8.46 (d, 1H), 10.70 (br, 1H) and 11.72 (br, 1H).

Embodiment 181

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-carbonyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-carbonyl }-Toluidrin (103mg, 91%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes K thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 451 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.74 (m, 4H), 1.94 (m, 4H), 2.32 (s, 3H), 3.11 (s, 3H), 3.32 (p, 1H), 4.66 (br, 1H), 6.62 (s, 1H), 7.32 (d, 1H), 7.62 (d, 1H), 8.22 (br, 1H), 8.40 (d, 1H) and 11.68 (br, 1H).

Embodiment 182

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-urea (86mg, 73%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-(97mg 0.25mmol) prepares according to common processes M thiazole-4-guanidine-acetic acid.

LC-MS (m/z): 473 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.40 (t, 2H), 1.72 (m, 4H), 1.92 (m, 4H), 2.16 (s, 6H), 2.35 (s, 3H), 2.88 (m, 2H), 3.13 (s, 2H), 3.70 (p, 1H), 6.90 (s, 1H), 7.36 (d, 1H), 7.67 (s, 1H), 8.20 (d, 1H), 8.44 (br, 1H), 8.92 (br, 1H), 10.26 (br, 1H) and 11.90 (br, 1H).

Embodiment 183

(3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-urea groups)-acetic acid

(3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-urea groups)-acetic acid (96mg, 83%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-guanidine-acetic acid (97mg, 0.25mmol) and glycine methyl ester (48mg, 0.5mmol) according to common processes M, succeeded by utilizing common processes J hydrolysis to prepare.

LC-MS (m/z): 460 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.70 (m, 4H), 1.90 (m, 4H), 2.38 (s, 3H), 3.49 (s, 2H), 3.71 (s, 2H), 3.84 (p, 1H), 6.78 (s, 1H), 7.34 (d, 1H), 7.73 (s, 1H), 8.36 (d, 1H), 8.42 (br, 1H), 8.94 (br, 1H), 9.86 (br, 1H), 10.26 (br, 1H) and 11.64 (br, 1H).

Embodiment 184

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester hydrochloride

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester hydrochloride (103mg, 87%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-guanidine-acetic acid (97mg, 0.25mmol) and 2-N, (0.05mL is 0.5mmol) according to common processes M, the preparation succeeded by handling with the ethereal solution of HCl for the N-dimethyl ethanol.

LC-MS (m/z): 474 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.42 (t, 2H), 1.74 (m, 4H), 1.92 (m, 4H), 2.28 (s, 6H), 2.39 (s, 3H), 2.96 (m, 2H), 3.24 (s, 2H), 3.74 (p, 1H), 6.86 (s, 1H), 7.34 (d, 1H), 7.72 (s, 1H), 8.44 (d, 1H), 9.12 (br, 1H), 10.34 (br, 1H) and 11.22 (br, 1H).

Embodiment 185

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-N ', N '-dimethyl methyl acid amides

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-N ', N '-dimethyl methyl acid amides (104mg, 89%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) and the dimethylamino SULPHURYL CHLORIDE (0.06mL is 0.5mmol) according to common processes T preparation.

LC-MS (m/z): 466 (M+1) ^{+ 1}H NMR (400MHz, CDCl ³): δ 1.72 (m, 4H), 1.88 (m, 4H), 2.36 (s, 3H), 2.75 (s, 6H), 3.72 (p, 1H), 4.22 (d, 2H), 6.74 (s, 1H), 7.03 (br, 1H), 7.34 (d, 1H), 7.70 (s, 1H), 8.42 (d, 1H), 9.72 (br, 1H) and 11.66 (br, 1H).

Embodiment 186

3-[{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-(2-methoxycarbonyl-ethyl)-amino]-the propionic acid methyl ester

3-[{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-(2-methoxycarbonyl-ethyl)-amino]-propionic acid methyl ester (114mg, 86%) be to prepare like this, be about to 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) with methyl acrylate (0.1mL, 1.1mmol) and Cs ₂CO ₃(325mg, THF 1.0mmol) (5mL) solution heats 2h down at 60 ℃, succeeded by column purification [silicon-dioxide, DCM: ethyl acetate (80: 20 to 20: 80)].

LC-MS (m/z): 531 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.68 (m, 4H), 1.84 (m, 2H), 2.04 (m, 2H), 2.16 (s, 6H), 2.36 (s, 3H), 2.45 (t, 4H), 3.66 (m, 4H), 3.72 (p, 1H), 4.48 (s, 2H), 6.78 (s, 1H), 7.34 (d, 1H), 7.66 (s, 1H), 8.44 (d, 1H), 10.54 (br, 1H) and 11.62 (br, 1H).

Embodiment 187

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-methoxycarbonyl methyl-amino)-the acetic acid methyl ester

([2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-methoxycarbonyl methyl-amino)-acetic acid methyl ester (99mg, 79%) be to prepare like this, be about to 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) usefulness methyl bromoacetate (0.04mL, 0.5mmol) handle 2h with DCM (5mL) solution of pyridine (0.082mL) down at 60 ℃, succeeded by column purification [silicon-dioxide, DCM: ethyl acetate (80: 20 to 20: 80)].

LC-MS (m/z): 503 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.53 (m, 4H), 1.76 (m, 4H), 2.18 (s, 3H), 2.59-2.74, (m, 6H), 3.50 (s, 6H), 3.62 (m, 1H), 6.69 (s, 1H), 7.18 (d, 1H), 7.54 (s, 1H), 8.18 (d, 1H), 10.58 (br, 1H) and 11.28 (br, 1H).

Embodiment 188

(carboxymethyl-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-acetic acid

(carboxymethyl-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-acetic acid (44mg, 88%) be that (50mg is 0.1mmol) according to common processes J preparation from ({ 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-methoxycarbonyl methyl-amino)-acetic acid methyl ester.

LC-MS (m/z): 474 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.53 (m, 4H), 1.76 (m, 4H), 2.32 (s, 3H), 2.63 (s, 2H), 2.74 (s, 4H), 3.72 (m, 1H), 6.76 (s, 1H), 7.28 (d, 1H), 7.66 (s, 1H), 8.38 (d, 1H), 9.66 (br, 1H), 10.08 (br, 2H) and 11.46 (br, 1H).

Embodiment 189

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-2-dimethylamino-ethanamide

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-2-dimethylamino-ethanamide (86mg, 78%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) and N, (0.30mg 0.30mmol) prepares according to common processes K the N-N-methylsarcosine.

LC-MS (m/z): 444 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.70 (m, 4H), 1.92 (m, 4H), 2.30 (s, 3H), 2.82 (s, 3H), 2.96 (s, 3H), 3.75 (s, 2H), 3.82 (m, 1H), 4.28 (d, 2H), 6.98 (s, 1H), 7.38 (d, 1H), 7.67 (s, 1H), 8.02 (d, 1H), 8.44 (br, 1H), 9.22 (br, 1H) and 11.44 (br, 1H).

Embodiment 190

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-guanidine radicals methyl-thiazol-2-yl)-urea

To 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, THF 0.25mmol) (10mL) solution add pyrroles-1-carbonamidine (54mg, 0.50mmol) and DIEA (90mL).Reaction mixture is heated 3h down at 60 ℃, concentrate.Crude product obtains 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-guanidine radicals methyl-thiazol-2-yl)-urea (88mg, 88%) through purification by flash chromatography [silicon-dioxide, DCM: ethyl acetate (50: 50 to 10: 90)].

LC-MS (m/z): 401 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.50 (m, 4H), 1.72 (m, 4H), 2.23 (s, 3H), 3.08 (q, 1H), 3.62 (p, 1H), 4.26 (br, 2H), 4.32 (t, 2H), 6.71 (s, 1H), 7.16 (d, 1H), 7.48 (s, 1H), 7.96 (br, 1H), 8.12 (d, 1H), 8.70 (br, 1H) and 10.92 (br, 1H).

Embodiment 191

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(4-S-methyl-2,5-dioxo-imidazolidine-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(4-S-methyl-2,5-dioxo-imidazolidine-1-ylmethyl)-thiazol-2-yl]-urea (78mg, 69%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (358mg, 1.0mmol) and the t-Boc-L-L-Ala (100mg is 0.80mmol) according to common processes U preparation.

LC-MS (m/z): 456 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.43 (d, 3H), 1.64 (m, 4H), 1.88 (m, 4H), 2.35 (s, 3H), 3.56 (q, 1H), 3.74 (p, 1H), 4.73 (s, 2H), 5.52 (br, 1H), 6.84 (s, 1H), 7.32 (d, 1H), 7.68 (s, 1H), 8.40 (d, 1H), 9.84 (br, 1H) and 11.44 (br, 1H).

Embodiment 192

1-(4-{[pair-(3H-imidazol-4 yl methyl)-amino]-methyl }-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(4-{[pair-(3H-imidazol-4 yl methyl)-amino]-methyl }-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (110mg, 85%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) and imidazoles-2-formaldehyde (48mg is 0.50mmol) according to common processes O preparation.

LC-MS (m/z): 519 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.58 (m, 4H), 1.84 (m, 4H), 2.34 (s, 3H), 3.10 (s, 2H), 3.51 (s, 4H), 3.64 (p, 1H), 6.62 (s, 1H), 6.84 (s, 1H), 7.08 (s, 1H), 7.11 (d, 1H), 7.66 (d, 1H), 7.70 (s, 1H), 7.83 (d, 1H), 8.36 (d, 1H), 8.70 (br, 2H), 9.74 (br, 1H) and 11.30 (br, 1H).

Embodiment 193

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(N ', N ', N ", N " and tetramethyl--guanidine radicals methyl)-thiazol-2-yl]-urea

To 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) DMF solution add HBTU (94mg, 0.25mmo1) and DIEA (90 μ L).Reaction mixture is stirred 2h under rt.Reaction mixture is poured in the water (30mL), with ethyl acetate extraction (3 * 25mL).With organic layer washing (water, salt solution), dry (Na ₂SO ₄), concentrate in a vacuum.Crude product is through purification by flash chromatography [silicon-dioxide, DCM: ethyl acetate (50: 50 to 10: 90)], obtain 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(N ', N ', N ', N " tetramethyl--guanidine radicals methyl)-thiazol-2-yl]-urea (92mg, 81%).

LC-MS (m/z): 457 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.66 (m, 4H), 1.82 (m, 2H), 1.94 (m, 2H), 2.37 (s, 3H), 2.96 (s, 12H), 3.76 (p, 1H), 4.32 (s, 2H), 6.80 (s, 1H), 7.38 (d, 1H), 7.70 (s, 1H), 8.38 (d, 1H), 10.54 (br, 1H) and 11.58 (br, 1H).

Embodiment 194

2-amino-ethyl sulfonic acid 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-acid amides

2-amino-ethyl sulfonic acid 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-acid amides (104mg, 83%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg, 0.25mmol) and 2-(1,3-dioxo-1,3-dihydro-isoindole-2-yl)-(70mg 0.25mmol) prepares according to common processes T ethyl sulfonyl chloride.This intermediate and excessive hydrazine (0.2mL, the 1.0M solution among the THF) heating are gone protection.

LC-MS (m/z): 466 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.68 (m, 4H), 1.92 (m, 4H), 2.38 (s, 3H), 3.22 (t, 2H), 3.68 (m, 2H), 3.76 (p, 1H), 4.08 (s, 2H), 4.84 (br, 1H), 5.38 (br, 2H), 6.76 (s, 1H), 7.36 (d, 1H), 7.74 (s, 1H), 8.48 (d, 1H), 10.22 (br, 1H) and 11.36 (br, 1H).

Embodiment 195

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-2-methanesulfonamido-ethanamide

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-2-methanesulfonamido-ethanamide (103mg, 84%) be from 2-amino-N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-ethanamide (1 04mg, 0.25mmol) and methylsulfonyl chloride (0.04mL is 0.5mmol) according to common processes L preparation.

LC-MS (m/z): 494 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.70 (m, 4H), 1.88 (m, 4H), 2.36 (s, 3H), 3.28 (t, 2H), 3.38 (s, 3H), 3.74 (p, 1H), 4.16 (d, 2H), 6.84 (s, 1H), 6.96 (br, 1H), 7.38 (d, 1H), 7.44 (br, 1H), 7.69 (s, 1H), 8.36 (d, 1H), 10.58 (br, 1H) and 11.28 (br, 1H).

Embodiment 196

[(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carbamyl)-methyl]-amino }-acetic acid

[(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carbamyl)-methyl]-amino }-acetic acid (44mg; 88%) be that (50mg is 0.1mmol) according to common processes J preparation from ({ 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-methoxycarbonyl methyl-amino)-acetic acid methyl ester.

LC-MS (m/z): 474 (M+1) ^{+ 1}H NMR (400MHz, CD ₃0D): δ 1.58 (m, 4H), 1.84 (m, 4H), 2.31 (s, 3H), 2.79 (d, 2H), 3.58 (d, 2H) 3.70 (m, 1H), 4.18 (s, 2H), 4.96 (br, 1H), 6.82 (s, 1H), 7.03 (br, 1H), 7.30 (d, 1H), 7.72 (s, 1H), 8.44 (d, 1H), 9.66 (br, 1H), 10.08 (br, 1H) and 11.46 (br, 1H).

Embodiment 197

[(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carbamyl)-methyl]-amino }-the acetic acid methyl ester

[(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carbamyl)-methyl]-amino }-acetic acid methyl ester (44mg; 88%) be to prepare like this; be about to 2-amino-N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-ethanamide (104mg; 0.25mmol) usefulness methyl bromoacetate (0.023mL; 0.25mmol) THF (5mL) solution handle down 2h at 60 ℃; succeeded by column purification [silicon-dioxide, DCM: ethyl acetate (80: 20 to 20: 80)].

LC-MS (m/z): 488 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.64 (m, 4H), 1.82 (m, 4H), 2.38 (s, 3H), 2.66 (s, 2H), 2.78, (s, 2H), 3.18 (s, 2H), 3.52 (s, 3H), 3.72 (m, 1H), 6.76 (s, 1H), 7.06 (br, 1H), 7.28 (d, 1H), 7.66 (s, 1H), 8.38 (d, 1H), 8.86 (br, 1H), 9.74 (br, 1H) and 11.46 (br, 1H).

Embodiment 198

3-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-propionic acid

3-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-propionic acid (85mg; 87%) be that (101mg is 0.20mmol) according to common processes J preparation from 3-({ 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-propionic acid methyl ester.

LC-MS (m/z): 495 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.74 (m, 4H), 1.88 (m, 4H), 2.33 (s, 3H), 3.12 (t, 2H), 3.48 (t, 2H), 3.72 (p, 1H), 3.88 (d, 2H), 6.72 (s, 1H), 7.36 (d, 1H), 7.68 (s, 1H), 8.42 (d, 1H), 9.54 (br, 1H), 10.88 (br, 1H), 11.12 (br, 1H) and 11.54 (br, 1H).

Embodiment 199

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-2-methylsulfonyl-ethanamide

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-2-methylsulfonyl-ethanamide (103mg; 84%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg; 0.25mmol) and methylsulfonyl acetic acid (55mg is 0.4mmol) according to common processes T preparation.

LC-MS (m/z): 479 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.68 (m, 4H), 1.84 (m, 4H), 2.35 (s, 3H), 2.78 (s, 2H), 3.12 (s, 3H), 3.86 (m, 1H), 4.08 (d, 2H), 6.89 (s, 1H), 7.04 (br, 1H), 7.37 (d, 1H), 7.80 (s, 1H), 8.24 (d, 1H), 8.52 (br, 1H) and 11.36 (br, 1H).

Embodiment 200

1-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperidines-S-3-carboxylic acid ethyl ester

1-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperidines-S-3-carboxylic acid ethyl ester (107mg; 86%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and piperidines-S-3-carboxylic acid ethyl ester (40mg is 0.25mmol) according to common processes O preparation.

LC-MS (m/z): 499 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.22 (t, 3H), 1.63-1.70 (m, 6H), 1.89 (m, 4H), 2.22 (m, 1H), 2.35 (s, 3H), 2.60 (m, 2H), 2.84 (m, 2H), 3.00 (d, 2H), 3.55 (m, 2H), 3.72 (p, 1H), 4.10 (q, 2H), 6.67 (s, 1H), 7.33 (d, 1H), 7.68 (s, 1H), 8.40 (br, 1H), 10.50 (br, 1H) and 11.50 (br, 1H).

Embodiment 201

1-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperidines-S-3-carboxylic acid

1-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperidines-S-3-carboxylic acid (104mg, 81%) be from 1-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-(135mg 0.25mmol) prepares according to common processes J piperidines-S-3-carboxylic acid ethyl ester.

LC-MS (m/z): 471 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.58-1.64 (m, 4H), 1.84-1.96 (m, 6H), 2.16 (m, 1H), 2.28 (s, 3H), 2.80 (m, 1H), 3.05 (m, 1H), 3.34-3.49 (m, 2H), 3.66 (d, 1H), 3.93 (m, 1H), 4.34-4.50 (m, 2H), 4.70 (m, 1H), 6.83 (s, 1H), 7.36 (d, 1H), 7.60 (s, 1H), 8.25 (d, 1H), 9.00 (br, 1H), 10.20 (br, 1H) and 11.36 (br, 1H).

Embodiment 202

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-(tetrahydrochysene-pyrans-4-yl)-acetic acid methyl ester

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-(tetrahydrochysene-pyrans-4-yl)-acetic acid methyl ester (113mg; 88%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and amino-(tetrahydrochysene-pyrans-4-yl)-acetic acid methyl ester (44mg is 0.25mmol) according to common processes O preparation.

LC-MS (m/z): 515 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.42 (m, 4H), 1.66-1.73 (m, 4H), 1.80-193 (m, 4H), 2.35 (s, 3H), 3.14 (d, 2H), 3.32 (t, 2H), 3.64 (t, 2H), 3.72 (p, 1H), 3.78 (d, 2H), 3.92 (s, 3H), 6.24 (br, 1H), 6.64 (s, 1H), 7.32 (d, 1H), 7.68 (s, 1H), 8.42 (br, 1H), 9.78 (br, 1H) and 11.50 (br, 1H).

Embodiment 203

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-(tetrahydrochysene-pyrans-4-yl)-acetic acid

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-(tetrahydrochysene-pyrans-4-yl)-acetic acid (87mg, 87%) be that (128mg is 0.25mmol) according to common processes J preparation from ({ 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-amino)-(tetrahydrochysene-pyrans-4-yl)-acetic acid methyl ester.

LC-MS (m/z): 501 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.48 (m, 4H), 1.68-1.75 (m, 4H), 1.82-192 (m, 4H), 2.36 (s, 3H), 3.36 (d, 2H), 3.44 (t, 2H), 3.68 (t, 2H), 3.74 (p, 1H), 3.82 (d, 2H), 5.24 (br, 1H), 6.76 (s, 1H), 7.34 (d, 1H), 7.71 (s, 1H), 8.44 (d, 1H), 9.62 (br, 1H), 10.38 (br, 1H) and 11.20 (br, 1H).

Embodiment 204

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[(2-morpholine-4-base-ethylamino)-methyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[(2-morpholine-4-base-ethylamino)-methyl]-thiazol-2-yl }-urea (97mg; 82%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and 2-morpholine-4-base-ethylamine (35mg is 0.25mmol) according to common processes O preparation.

LC-MS (m/z): 472 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.66 (m, 4H), 1.88 (m, 4H), 2.33 (s, 3H), 2.38 (m, 2H), 2.50 (t, 2H), 2.80 (t, 2H), and 3.59-3.64 (m, 6H), 3.70p, 1H), 3.85 (m, 2H), 5.88 (br, 1H), 6.58 (s, 1H), 7.32 (d, 1H), 7.66 (s, 1H), 8.42 (d, 1H), 10.08 (br, 1H) and 11.28 (br, 1H).

Embodiment 205

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-morpholine-4-ylmethyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-morpholine-4-ylmethyl-thiazol-2-yl)-urea (83mg; 78%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and (30mg; 0.3mmol) and morpholine (0.25mL is 0.3mmol) according to common processes O preparation.

LC-MS (m/z): 429 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.62-1.80 (m, 4H), 1.80-1.94 (m, 4H), 2.35 (s, 3H), 2.50 (m, 4H), 3.53 (s, 2H), 3.70 (t, 4H), 3.75 (m, 1H), 6.70 (s, 1H), 7.34 (d, 1H), 7.69 (s, 1H), 8.40 (d, 1H), 9.75 (br, 1H) and 11.58 (br, 1H).

Embodiment 206

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(3-oxo-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(3-oxo-piperazine-1-ylmethyl)-thiazol-2-yl]-urea (79mg; 82%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and piperazine-2-ketone (30mg is 0.30mmol) according to common processes O preparation.

LC-MS (m/z): 442 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.60-1.74 (m, 4H), 1.80-1.94 (m, 4H), 2.35 (s, 3H), 2.67 (t, 2H), 3.30 (s, 2H), 3.38 (m, 2H), 3.58 (s, 2H), 3.73 (p, 1H), 6.66 (s, 1H), 7.32 (d, 1H), 7.67 (s, 1H), 7.78 (br, 1H), 8.38 (d, 1H), 10.44 (br, 1H) and 11.40 (br, 1H).

Embodiment 207

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-the acetic acid ethyl ester

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-acetic acid ethyl ester (79mg; 82%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and piperazine-1-base-acetic acid ethyl ester (43mg is 0.25mmol) according to common processes O preparation.

LC-MS (m/z): 514 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.28 (t, 3H), 1.46-1.62 (m, 4H), 1.66-1.86 (m, 4H), 2.35 (s, 3H), 3.28 (m, 2H), 3.42 (s, 2H), 3.40-3-64 (m, 4H), 3.83 (m, 1H), 3.92 (s, 2H), 4.12 (m, 2H), 4.48 (s, 2H), 6.84 (s, 1H), 7.29 (d, 1H), 7.67 (s, 1H), 8.28 (d, 1H), 11.14 (br, 1H) and 11.62 (br, 1H).

Embodiment 208

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-acetic acid

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-acetic acid (40mg, 83%) be from (4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl-piperazine-1-yl)-(52mg is 0.10mmol) according to common processes J preparation for the acetic acid ethyl ester.

LC-MS (m/z): 486 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.44-1.58 (m, 4H), 1.62-1.80 (m, 4H), 2.22 (s, 3H), 2.98 (s, 2H), 3.18 (m, 2H), 3.62 (p, 1H), 4.02-4.18 (m, 8H), 7.00 (s, 1H), 7.22 (d, 1H), 7.58 (s, 1H), 8.18 (d, 1H), 9.54 (br, 1H), 10.78 (br, 1H) and 11.44 (br, 1H).

Embodiment 209

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-the propionic acid ethyl ester

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-propionic acid ethyl ester (118mg; 89%) be from 2-[3-(2-1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(4-formyl radical-thiazol-2-yl)-urea (89mg; 0.25mmol) and 3-piperazine-1-base-propionic acid ethyl ester (61mg is 0.30mmol) according to common processes O preparation.

LC-MS (m/z): 528 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.24 (t, 3H), 1.44-1.64 (m, 4H), 1.64-1.80 (m, 4H), 2.36 (s, 3H), 3.22-3.38 (m, 6H), 3.40-3-64 (m, 4H), 3.83 (m, 1H), 3.96 (m, 2H), 4.08 (m, 2H), 4.58 (s, 2H), 6.97 (s, 1H), 7.14 (d, 1H), 7.64 (s, 1H), 8.16 (d, 1H), 11.04 (br, 1H) and 11.22 (br, 1H).

Embodiment 210

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-propionic acid

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-piperazine-1-yl)-propionic acid (38mg, 76%) be from 3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl-piperazine-1-yl)-(53mg is 0.10mmol) according to common processes J preparation for the propionic acid ethyl ester.

LC-MS (m/z): 500 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.42-1.60 (m, 4H), 1.64-1.78 (m, 4H), 2.26 (s, 3H), and 3.38-3.44 (m, 6H), 3.48-3.66 (m, 4H), 3.77 (m, 1H), 4.02 (m, 2H), 4.64 (s, 2H), 6.88 (s, 1H), 7.30 (d, 1H), 7.73 (s, 1H), 8.28 (d, 1H), 9.88 (br, 1H), 10.38 (br, 1H) and 11.34 (br, 1H).

Embodiment 211

(3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-urea groups)-acetic acid

(3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-urea groups)-acetic acid methyl ester (106mg, 90%) be from 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-guanidine-acetic acid (97mg, 0.25mmol) and glycine methyl ester (48mg is 0.5mmol) according to common processes M preparation.

LC-MS (m/z): 460 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.73 (m, 4H), 1.88 (m, 4H), 2.36 (s, 3H), 3.46 (s, 2H), 3.66 (s, 2H), 3.78 (p, 1H), 6.74 (s, 1H), 7.36 (d, 1H), 7.71 (s, 1H), 8.28 (d, 1H), 8.44 (br, 1H), 8.92 (br, 1H), 9.96 (br, 1H) and 11.68 (br, 1H).

Embodiment 212

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2,5-dioxo-imidazolidine-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2,5-dioxo-imidazolidine-1-ylmethyl)-thiazol-2-yl]-urea (78mg, 69%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (358mg, 1.0mmol) and the t-Boc-glycine (90mg is 0.80mmol) according to common processes U preparation.

LC-MS (m/z): 442 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.66 (m, 4H), 1.90 (m, 4H), 2.38 (s, 3H), 3.43 (s, 2H), 3.76 (p, 1H), 4.24 (s, 2H), 5.48 (br, 1H), 6.78 (s, 1H), 7.34 (d, 1H), 7.72 (s, 1H), 8.44 (d, 1H), 9.66 (br, 1H) and 11.64 (br, 1H).

Embodiment 213

4-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-phenylformic acid

4-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-phenylformic acid (78mg; 58%) be that (90mg 0.25mmol) prepares according to common processes T from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 543 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.73 (m, 4H), 1.88 (m, 4H), 2.33 (s, 3H), 3.68 (m, 2H), 3.74 (p, 1H), 5.88 (br, 1H), 6.82 (s, 1H), 7.36 (d, 1H), 7.48 (d, 2H), 7.68 (d, 2H), 7.74 (s, 1H), 8.48 (d, 1H), 9.76 (br, 1H), 10.38 (br, 1H) and 11.44 (br, 1H).

Embodiment 214

3-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-the propionic acid methyl ester

3-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-sulfamyl)-propionic acid methyl ester (116mg; 91%) be from 1-(4-amino methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (90mg; 0.25mmol) and 3-chlorosulfonyl-propionic acid methyl ester (47mg is 0.25mmol) according to common processes T preparation.

LC-MS (m/z): 509 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.73 (m, 4H), 1.88 (m, 4H), 2.33 (s, 3H), 3.04 (t, 2H), 3.42 (t, 2H), 3.74 (p, 1H), 4.06 (d, 2H), 4.26 (s, 3H), 6.58 (s, 1H), 7.32 (d, 1H), 7.72 (s, 1H), 8.48 (d, 1H), 9.76 (br, 1H), 10.38 (br, 1H) and 11.52 (br, 1H).

Embodiment 215

2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (154mg, 80%) be from 2-amino-4 methyl-phenyl-cyclopentyl-ketone (102mg, 0.5mmol) and ethyl 2-amino-4-thiazolyl acetate (112mg is 0.5mmol) according to common processes D preparation.

LC-MS(m/z)：416(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.26(t，3H)，1.69(m，4H)，1.88(m，4H)，2.41(s，3H)，3.70(s，2H)，3.72(m，1H)，4.18(m，2H)，6.71(s，1H)，6.88(d，1H)，7.7.81(d，1H)，8.44(s，1H)，9.48(br，1H)，11.82(br，1H).

Embodiment 216

2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (175mg, 90%) be that (208mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS(m/z)：388(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.74(m，4H)，1.87(m，4H)，2.35(s，3H)，3.56(s?2H)，3.84(m，1H)，6.85(s，1H)，6.96(d，1H)，7.95(d，1H)，8.17(s，1H)，10.96(br，1H)，12.22(br，1H)，12.40(br，1H).

Embodiment 217

2-[3-(2-pentamethylene carbonyl-5-fluoro-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (168mg, 80%) be from 2-amino-4-methyl fluoride-phenyl-cyclopentyl-ketone (103mg, 0.5mmol) and ethyl 2-amino-4-thiazolyl acetate (112mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：420(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.26(t，3H)，1.69(m，4H)，1.88(m，4H)，3.67(m，1H)，3.72(s，2H)，4.18(m，2H)，6.68(d，1H)，6.75(m，1H)，7.93(t，1H)，8.44(d，1H)，10.20(br，1H)，11.90(br，1H).

Embodiment 218

2-[3-(2-pentamethylene carbonyl-5-fluoro-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (180mg, 92%) be that (209mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-5-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS(m/z)：392(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.61(m，4H)，1.74(m，2H)，1.87(m，2H)，3.57(s?2H)，3.84(m，1H)，6.88(s，1H)，6.98(t，1H)，8.21(m，2H)，11.23(br，1H)，12.20(br，1H).

Embodiment 219

2-[3-(4-bromo-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(4-bromo-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (192mg, 80%) be from 2-amino-5-bromo-phenyl-cyclopentyl-ketone (134mg, 0.5mmol) and ethyl 2-amino-4-thiazolyl acetate (112mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：481(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.27(t，3H)，1.70(m，4H)，1.87(m，4H)，3.67(m，1H)，3.72(s，2H)，4.19(m，2H)，6.70(s，1H)，7.59(dd，1H)，7.99(s，1H)，8.53(br，1H)，9.59(br，1H)，11.56(br，1H).

Embodiment 220

2-[3-(4-bromo-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(4-bromo-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (204mg, 90%) be that (240mg is 0.5mmol) according to common processes J preparation from { 2-[3-(4-bromo-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS(m/z)：453(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.72(m，4H)，1.82(m，4H)，3.54(s?2H)，3.78(m，1H)，6.86(s，1H)，7.72(br，1H)，8.10(br，1H)，8.22(s，1H)，10.65(br，1H)，11.70(br，1H)，12.40(br，1H).

Embodiment 221

4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-the acetic acid ethyl ester

4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid ethyl ester (157mg; 72%) be from ethyl (4-methyl carboxyl)-2-pentamethylene anilid (138mg; 0.5mmol) and 5-chloro-thiazol-2-yl amine (81mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：436(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ0.90(t，3H)，1.62(m，2H)，1.46(m，2H)，1.62(m，4H)，3.73(s，2H)，3.85(m，1H)，4.15(q，2H)，7.42(s，1H)，7.48(d，1H)，7.98(s，1H)，8.20(d，1H)，10.79(br，1H)，12.10(br?1H).

Embodiment 222

4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid

4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid (180mg, 88%) be that (218mg is 0.5mmol) according to common processes J preparation from { 4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid ethyl ester.

LC-MS(m/z)：408(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.73(m，4H)，1.89(m，4H)，3.35(s，2H)，3.85(m，1H)，7.42s，1H)，7.47(d，1H)，7.96(s，1H)，8.20(d，1H)，10.79(s，1H)，12.20(br，1H)，

Embodiment 223

2-{4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-N-(2-methylsulfonyl-ethyl)-ethanamide

2-{4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-N-(2-methylsulfonyl-ethyl)-ethanamide (180mg; 70%) be from { 4-[3-(5-chloro-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid (204mg; 0.5mmol) and 2-methylsulfonyl-ethylamine (62mg is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：514(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.75(m，4H)，1.91(m，4H)，2.97(s，3H)，3.07(q，2H)，3.23(t，2H)，3.42(s，2H)，3.84(m，1H)，7.42(s，1H)，7.44(d，1H)，7.94(s，1H)，8.18(d，1H)，8.35(t，1H)，10.77(s，1H)，12.01(br，1H)，

Embodiment 224

[2-(3-{2-pentamethylene carbonyl-4-[(2-methylsulfonyl-ethyl carbamyl)-methyl]-phenyl }-urea groups)-thiazole-4-yl]-the acetic acid ethyl ester

[2-(3-{2-pentamethylene carbonyl-4-[(2-methylsulfonyl-ethyl carbamyl)-methyl]-phenyl }-urea groups)-thiazole-4-yl]-acetic acid ethyl ester (174mg; 65%) be from 2-(4-amino-3-pentamethylene carbonyl-phenyl)-N-(2-methylsulfonyl-ethyl)-ethanamide (176mg; 0.5mmol) and (2-amino-thiazolyl--4-yl)-acetic acid ethyl ester (112mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：565(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.28(t，3H)，1.65(m，4H)，1.79(m，2H)，1.88(m，2H)，3.01(s，3H)，3.31(t，2H)，3.53(s，2H)，3.68(s，2H)，3.83(m，1H)，4.20(m，3H)，7.42(s，1H)，7.44(d，1H)，7.94(s，1H)，8.18(d，1H)，8.35(t，1H)，10.77(s，1H)，12.01(br，1H)，

Embodiment 225

2-(3-{2-pentamethylene carbonyl-4-[2-methylsulfonyl-ethyl carbamyl)-methyl]-phenyl }-urea groups)-thiazole-4-base-acetic acid

2-(3-{2-pentamethylene carbonyl-4-[2-methylsulfonyl-ethyl carbamyl)-methyl]-phenyl }-urea groups)-thiazole-4-base-acetic acid (214mg; 80%) be from 2-(3-{2-pentamethylene carbonyl-4-[2-methylsulfonyl-ethyl carbamyl)-methyl]-phenyl }-urea groups)-(282mg 0.5mmol) prepares according to common processes J thiazole-4-base-acetic acid ethyl ester.

LC-MS(m/z)：537(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.65(m，4H)，1.79(m，2H)，1.88(m，2H)，2.97(s，3H)，3.22(t，2H)，3.45(m，2H)，3.47(s，2H)，3.56(s，2H)，3.82(m，1H)，6.84(s，1H)，7.42(d，1H)，7.92(s，1H)，8.18(d，1H)，8.33(t，1H)，10.70(s，1H)，11.84(br，1H)，

Embodiment 226

[3-pentamethylene carbonyl-4-(3-[1,3,4] thiadiazoles-2-base-urea groups)-phenyl]-the acetic acid ethyl ester

3-pentamethylene carbonyl-4-(3-[1,3,4] thiadiazoles-2-base-urea groups)-phenyl]-acetic acid ethyl ester (147mg, 73%) be from (4-amino-3-pentamethylene carbonyl-phenyl)-acetic acid ethyl ester (138mg, 0.5mmol) and [1,3,4] thiadiazoles-(60mg 0.6mmol) prepares according to common processes D 2-base amine.

LC-MS(m/z)：403(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.27(t，6H)，1.67(m，4H)，1.91(m，4H)，3.64(s，2H)，3.77(m，1H)，4.17(m，4H)，7.46(d，1H)，7.89(s，2H)，8.47(s，1H)，8.77(s，1H)，10.40(br，1H)，11.89(br，1H).

Embodiment 227

1-[2-pentamethylene carbonyl-4-(2-morpholine-4-base-2-oxo-ethyl)-phenyl]-3-thiazol-2-yl-urea

1-[2-pentamethylene carbonyl-4-(2-morpholine-4-base-2-oxo-ethyl)-phenyl]-3-thiazol-2-yl-urea (151mg, 68%) be from [3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-acetic acid (186mg, 0.5mmol) and morpholine (44mg is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：443(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃/DMSO-d ₆)：δ1.67(m，4H)，1.88(m，4H)，3.51(t，4H)，3.69(t，4H)，3.74(m，3H)，6.91(d，1H)，7.37(dd，1H)，7.64(d，1H)，7.84(s，1H)，8.52(br，2H)，11.32(br，1H).

Embodiment 228

1-{2-pentamethylene carbonyl-4-[2-(4-methyl-piperazine-1-yl)-2-oxo-ethyl]-phenyl }-3-thiazol-2-yl-urea

1-{2-pentamethylene carbonyl-4-[2-(4-methyl-piperazine-1-yl)-2-oxo-ethyl]-phenyl }-3-thiazol-2-yl-urea (137mg, 60%) be from [3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-acetic acid (186mg, 0.5mmol) and N methyl piperazine (50mg is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：456(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃/DMSO-d ₆)：δ1.67(m，4H)，1.89(m，4H)，2.29(s，3H)，3.51(t，4H)，3.61(s，2H)，3.69(m，5H)，6.92(d，1H)，7.38(d，1H)，7.58(s，1H)，7.84(s，1H)，8.53(d，1H)，11.56(br，1H)，11.67(br，1H).

Embodiment 229

2-[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-kharophen }-acetic acid

2-[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-kharophen }-ra-butyl acetate (158mg, 65%) be from [3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-acetic acid (186mg, 0.5mmol) and tert-butyl glycinate (60mg is 0.5mmol) according to common processes K preparation.(122mg 0.25mmol) with after the TFA hydrolysis, obtains { 2-[3-pentamethylene carbonyl-4-(3-thiazol-2-yl-urea groups)-phenyl]-kharophen }-acetic acid (86mg, 80%) with the ester intermediate.

LC-MS(m/z)：431(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃/DMSO-d ₆)：δ1.67(m，4H)，1.94(m，4H)，3.69(dd，2H)，3.82(m，3H)，3.95(t，1H)，6.99(m，1H)，7.32(dd，1H)，7.39(d，1H)，7.75(d，1H)，8.45(d，1H)，12.16(br，1H).

Embodiment 230

2-[3-(2-pentamethylene carbonyl-4-methyl carbamyl methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methyl carbamyl methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (153mg; 65%) be from 2-(4-amino-3-pentamethylene-carbonyl-phenyl)-N-methyl-ethanamide (130mg; 0.5mmol) and (2-amino-thiazolyl--4-yl)-acetic acid ethyl ester (112mg is 0.6mmol) according to common processes D preparation.(236mg 0.5mmol), obtains { 2-[3-(2-pentamethylene carbonyl-4-methyl carbamyl methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (167mg, 75%) according to common processes J ester hydrolysis intermediate.

LC-MS(m/z)：445(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.62(m，4H)，1.74(m，2H)，1.90(m，2H)，2.57(d，3H)，3.43(s，2H)，3.56(s，2H)，3.81(m，1H)，6.85(d，2H)，7.41(d，1H)，7.92(s，1H)，7.96(d，1H)，8.18(d，1H)，10.69(s，1H)，11.96(br，1H).

Embodiment 231

3-pentamethylene carbonyl-4-[3-(4-methyl carbamyl methyl-thiazol-2-yl)-urea groups]-phenyl }-the acetic acid ethyl ester

3-pentamethylene carbonyl-4-[3-(4-methyl carbamyl methyl-thiazol-2-yl)-urea groups]-phenyl }-acetic acid ethyl ester (153mg; 65%) be from (4-amino-3-pentamethylene-carbonyl-phenyl)-acetic acid ethyl ester (138mg; 0.5mmol) and 2-(2-amino-thiazolyl--4-yl)-N-methyl-ethanamide (103mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：473(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.26(t，3H)，1.70(m，4H)，1.86(m，2H)，1.92(m，2H)，2.81(d，3H)，3.62(s，2H)，3.65(s，2H)，3.77(m，1H)，4.16(q，2H)，6.65(s，1H)，6.71(br，1H)，7.44(dd，1H)，7.88(s，1H)，8.52(d，1H)，9.39(br，1H)，11.71(br，1H).

Embodiment 232

2-{3-pentamethylene carbonyl-4-[3-(4-methyl carbamyl methyl-thiazol-2-yl)-urea groups]-phenyl }-N-methyl-ethanamide

3-pentamethylene carbonyl-4-[3-(4-methyl carbamyl methyl-thiazol-2-yl)-urea groups]-phenyl }-acetic acid (155mg; 70%) be that (236mg is 0.5mmol) according to common processes J preparation from { 3-pentamethylene carbonyl-4-[3-(4-methyl carbamyl methyl-thiazol-2-yl)-urea groups]-phenyl }-acetic acid ethyl ester.According to common processes K make acid (222mg, 0.5mmol) with the coupling of 1N methylamine, obtain 2-{3-pentamethylene carbonyl-4-[3-(4-methyl carbamyl methyl-thiazol-2-yl)-urea groups]-phenyl-N-methyl-ethanamide (137mg, 60%).

LC-MS(m/z)：458(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃/DMSO-d ₆)：δ1.69(m，4H)，1.82(m，4H)，2.65(d，3H)，3.68(d，3H)，3.43(s，2H)，3.48(s，2H)，3.67(m，1H)，6.51(d，1H)，7.14(br，1H)，7.31(m，2H)，7.54(d，1H)，7.75(dd，1H)，8.31(d，1H)，11.13(br，1H).

Embodiment 233

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridine-2-base oxygen base)-ethyl]-thiazol-2-yl]-urea

Under 0 ℃, to 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-(0.38g, THF 1.0mmol) (5mL) solution drips 1.0M BH to acetic acid ₃-THF solution (3.0mL, 3.0mmol).After stirring 1h under 0 ℃, excessive BH3-THF title complex MeOH quencher.Concentrated solution under vacuum, purifying on silica gel with 1: 1 EtOAc/ hexane wash-out, obtains alcohol, is white powder, yield 80%.

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridine-2-base oxygen base)-ethyl]-thiazol-2-yl]-urea (30mg, 50%) be from 1-[2-(pentamethylene carbonyl-4-methyl-phenyl]-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-urea (0.05g, 0.134mmol), (0.013g is 0.143mmol) according to common processes P preparation for 2 hydroxy pyrimidine.

LC/MS(m/z)：451(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)d1.67-1.72(m，4H)，1.89-1.85(m，4H)，2.36(s，3H)，3.13(t，2H)，3.64-3.80(m，1H)，4.60(t，2H)，6.60(s，1H)，6.72(d，1H)，6.86(m，1H)，7.34(d，1H)，7.56(m，1H)，7.70(s，1H)，8.15(d，1H)，8.45(br，1H)，11.85(br，1H).

Embodiment 234

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-yl oxygen base)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-yl oxygen base)-ethyl]-thiazol-2-yl }-urea (50mg, 42%) be from 1-[2-(pentamethylene carbonyl-4-methyl-phenyl]-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-urea (0.10g, 0.27mmol) and the 4-pyridone (0.05g is 0.54mmol) according to common processes P preparation.

LC/MS(m/z)：451(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)d1.62-1.73(m，4H)，1.80-1985(m，4H)，2.37(s，3H)，2.85(t，2H)，3.87(t，2H)，3.75(br，1H)，6.52(s，1H)，7.46(d，2H)7.48(d，2H)，7.52(d，1H)，7.70(s，1H)，8.44(d，1H)，

Embodiment 235

5-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) the nicotinic acid methyl ester

5-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) nicotinic acid methyl ester (30mg, 4 4%) be from 1-[2-(pentamethylene carbonyl-4-methyl-phenyl]-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-urea (0.05g, 0.134mmol) and 5-hydroxy niacin methyl ester (0.04g is 0.27mmol) according to common processes P preparation.

LC/MS(m/z)：509(M+1) ⁺； ¹H?NMR(400MHz，CD ₃OD)d1.65-1.74(br，4H)，1.83-1.89(br，4H)，2.35(s，3H)，3.15(t，2H)，3.74(br，1H)，3.92(s，3H)，4.42(t，2H)，6.75(s，1H)，7.72(s，1H)，7.85(d，1H)，8.27(s，1H)，8.42(d，1H)，8.57(s，1H)，8.67(s，1H)，

Embodiment 236

5-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) nicotinic acid

5-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) nicotinic acid (23mg, 95%) be from 5-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl oxyethyl group) the nicotinic acid methyl ester (0.025g, 0.05mmol) and 2.5M LiOH (20ul) according to common processes J preparation.

LC/MS(m/z)：495(M+1) ⁺； ¹H?NMR(400MHz，CD ₃OD)d1.65-1.75(br，4H)，1.83-1.90(br，4H)，2.31(s，3H)，3.05(t，2H)，3.72-3.80(m，1H)，4.42(t，2H)，6.85(s，1H)，7.57(s，1H)，7.74(d，1H)，8.30(s，1H)，8.48(d，1H)，8.52(s，1H)，8.65(s，1H)，11.43(br，1H).

Embodiment 237

4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) benzoic acid methyl ester

4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) benzoic acid methyl ester (50mg, 37%) be from 1-[2-(pentamethylene carbonyl-4-methyl-phenyl]-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-urea (0.10g, 0.27mmol) and 4-hydroxy-benzoic acid methyl ester (0.08g is 0.54mmol) according to common processes P preparation.

LC/MS(m/z)：508(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)d1.64-1.78(m，4H)，1.82-1.90(m，4H)，2.32(s，3H)，3.04(t，2H)，3.60-3.85(m，1H)，3.92(s，3H)，4.32(t，2H)，6.81(s，1H)，6.98(d，2H)，7.33(d，1H)，7.80(s，1H)，7.86(d，2H)，8.15(br，1H)，10.70(br，1H)，11.88(br，1H).

Embodiment 238

4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) phenylformic acid

4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group) phenylformic acid (19mg, 96%) be from 4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl oxyethyl group) benzoic acid methyl ester (0.020g, 0.04mmol) and 2.5M LiOH (20uL) according to common processes J preparation.

LC/MS(m/z)：494(M+1) ⁺； ¹H?NMR(400MHz，DMSO)d1.65-1.78(m，4H)，1.80-1.92(m，4H)，2.32(s，3H)，3.04(t，2H)，3.60-3.85(m，1H)，4.34(t，2H)，6.82(s，1H)，7.01(d，2H)，7.36(d，2H)，7.81(s，1H)，7.86(d，2H)，8.13(br，1H)，8.88(s，1H)，10.66(br，1H).

Embodiment 239

[4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group)-phenyl] the acetic acid methyl ester

[4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group)-phenyl] acetic acid methyl ester (56mg, 40%) be from 1-[2-(pentamethylene carbonyl-4-methyl-phenyl]-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-urea (0.10g, 0.27mmol) and 4-hydroxyphenyl acetic acid methyl ester (0.09g is 0.54mmol) according to common processes P preparation.

LC/MS (m/z)：522(M+1) ⁺.

Embodiment 240

[4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group)-phenyl] acetic acid

[4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group)-phenyl] acetic acid (25mg, 86%) be from [4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group)-phenyl] the acetic acid methyl ester (0.03g, 0.06mmol) and 2.5M LiOH (20uL) according to common processes J preparation.

LC/MS(m/z)：508(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)d1.65-1.76(m，4H)，1.83-1.95(m，4H)，2.36(s，3H)，3.10(t，2H)，3.70-3.82(m，1H)，4.24(t，2H)，4.96-5.02(m，2H)，6.50(s，1H)，6.88(d，2H)，7.20(d，2H)，7.30(d，1H)，7.68(s，1H)，8.45(br，1H)，11.45(br，1H).

Embodiment 241

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-morpholine-4-base-ethyl)-thiazol-2-yl]-urea

Under 0 ℃, to 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-hydroxyl-ethyl)-thiazol-2-yl]-CH of urea (2.68mmol) ₂Cl ₂(20mL) solution adds Et ₃N (1.64mL, 11.70mmol), dimethyl sulfoxide (DMSO) (10mL) succeeded by sulphur trioxide-pyridine (1.46g, 9.21mmol).Reaction mixture is stirred 1h, can pour in the water (30mL) mixture CH then into ₂Cl ₂Extraction, with organic layer with 1.0N ammonium chloride (2 * 20mL), water (2 * 20mL), salt solution (1 * 20mL) washing, dry (Na ₂SO ₄), concentrate, obtain solid.(silicon-dioxide, hexane/EtOAc 20-50%), obtain aldehyde to solid, are white solid, yield 50% through the column chromatography purifying.

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-morpholine-4-base-ethyl)-thiazol-2-yl]-urea (15mg, 31%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-oxo-ethyl)-thiazol-2-yl]-urea (0.04g, 0.11mmol) and morpholine (0.009g is 0.11mmol) according to common processes O preparation.

LC/MS(m/z)：443(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.68-1.72(m，4H)，1.88-1.91(m，4H)，2.36(s，3H)，2.53(br，4H)，2.72(t，2H)，2.85(t，2H)，3.72-3.74(m，5H)，6.52(s，1H)，7.35(d，1H)，7.70(s，1H)，8.45(br，1H)，11.62(br，1H).

Embodiment 242

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazol-2-yl]-urea (23mg, 44%) be from (0.04g, 0.11mmol) and 4-ethylamino morpholine (0.014g is 0.11mmol) according to common processes O preparation.

LC/MS(m/z)：486(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.69-1.73(m，4H)，1.88-1.92(m，4H)，2.35(s，3H)，2.50(t，2H)，2.53(br，4H)，2.72(t，2H)，2.80(t，2H)，2.85(t，2H)，3.72-3.74(m，5H)，6.53(s，1H)，7.35(d，1H)，7.70(s，1H)，8.45(br，1H)，11.60(br，1H).

Embodiment 243

1-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-piperidines-3-carboxylic acid ethyl ester

1-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-piperidines-3-carboxylic acid ethyl ester (28mg, 50%) be from (0.04g, 0.11mmol) and (s)-(+)-(0.017g 0.11mmol) prepares according to common processes O piperidines-3-formic acid.

LC/MS (m/z)：528(M+1) ⁺.

Embodiment 244

1-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-piperidines-3-carboxylic acid

1-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-piperidines-3-carboxylic acid (18mg, 95%) be from 1-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl-ethyl)-piperidines-3-carboxylic acid ethyl ester (0.02g, 0.04mmol) and 2.5M LiOH (20uL) according to common processes J preparation.

LC/MS(m/z)：513(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.60-1.69(m，4H)，1.80-1.98(m，4H)，2.34(s，3H)，2.90-3.05(m，5H)，3.10-3.20(m，4H)，3.65-3.75(m，1H)，6.49(s，1H)，7.34(d，1H)，7.63(s，1H)，8.25(d，1H)，11.40(br，1H).

Embodiment 245

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-piperazine-1-base-ethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-piperazine-1-base-ethyl)-thiazol-2-yl]-urea (35mg, 70%) be from methylsulfonic acid 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl ester (0.06g, 0.13mmol) and piperazine (0.50g is 5.82mmol) according to common processes Z preparation.

LC/MS(m/z)：442(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.66-1.72(m，4H)，1.86-1.90(m，4H)，2.36(s，3H)，2.45-2.60(br，4H)，2.71(t，2H)，2.84(t，2H)，2.89-2.98(m，4H)，3.70-3.80(m，1H)，6.47(s，1H)，7.34(d，1H)，7.69(s，1H)，8.45(br，1H)，11.45(br，1H).

Embodiment 246

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(4-methylsulfonyl-piperazine-1-base-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(4-methylsulfonyl-piperazine-1-base-ethyl]-thiazol-2-yl }-urea (14mg; 40%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-piperazine-1-base-ethyl)-thiazol-2-yl]-urea (0.03g; 0.07mmol) and SULPHURYL CHLORIDE (0.008g is 0.068mmol) according to common processes T preparation.

LC/MS(m/z)：520(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.65-1.75(m，4H)，1.85-1.95(m，4H)，2.37(s，3H)，2.60-2.64(br，4H)，2.76-2.95(m，4H)，2.78(s，3H)，3.25(br，4H)，3.70-3.80(m，1H)，6.50(s，1H)，7.35(d，1H)，7.70(s，1H)，8.45(br，1H)，11.65(br，1H).

Embodiment 247

1-[4-(2-amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-[4-(2-amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.15g, 94%) be from 1-[4-(2-azido--ethyl)-thiazol-2-yl]-(0.17g 0.43mmol) prepares according to common processes T 3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC/MS(m/z)：373(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.68-1.74(m，4H)，1.88-1.93(m，4H)，2.36(s，3H)，2.84(t，2H)，3.28(t，2H)，3.72-3.80(m，1H)，4.5(br，2H)，6.47(s，1H)，7.34(d，1H)，7.69(s，1H)，8.55(d，1H)，11.34(br，1H).

Embodiment 248

3-(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethylamino)-propionic acid

Make 1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.03g, 0.08mmol) and succinyl oxide (0.02g, 0.16mmol) 2h that in 10mLDCM, refluxes.The concentration response thing, purifying on silica gel is used the 5%MeOH/EtOAc wash-out, obtains pure products (20mg, 53%).

LC/MS(m/z)：473(M+1?) ⁺； ¹H?NMR(400MHz，DMSO)δ1.60-1.75(m，4H)，1.85-1.92(m，4H)，2.38(s，3H)，2.67(t，2H)，3.28-3.32(m，4H)，3.80-3.92(br，1H)，4.02(t，2H)，6.70(s，1H)，7.38(d，1H)，7.83(s，1H)，8.15(d，1H)，10.65(br，1H).

Embodiment 249

(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethylamino)-the acetic acid methyl ester

To 1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.03g, 0.08mmol) 10mL DCM solution add methyl bromoacetate (0.01g, 0.08mmol) succeeded by Et3N (0.008g, 0.08mmol).After at room temperature stirring was spent the night, the concentration response thing through the flash chromatography on silica gel purifying, was used the 5%MeOH/EtOAc wash-out, obtains product, yield 50%.

LC/MS (m/z)：445(M+1) ⁺

Embodiment 250

(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethylamino)-acetic acid

(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethylamino)-acetic acid (18mg, 95%) be from (2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl-ethylamino)-the acetic acid ethyl ester (0.02g, 0.05mmol) and 2.5M LiOH (20uL) according to common processes J preparation.

LC/MS(m/z)：431(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.63-1.74(m，4H)，1.86-1.92(m，4H)，2.36(s，3H)，2.81(t，2H)，3.07(t，2H)，3.59(s，2H)，3.69-3.76(m，1H)，6.54(s，1H)，7.33(d，1H)，7.70(s，1H)，8.46(br，1H)，11.60(br，1H).

Embodiment 251

N-(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-ethanamide

Under 0 ℃, to 1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.05g, 0.13mmol) 10mL DCM solution add Acetyl Chloride 98Min. (0.02g, 0.27mmol) succeeded by pyridine (0.02g, 0.21mmol).After stirring 3h, the concentration response thing through the flash chromatography on silica gel purifying, with 50%EtOAc/ hexane wash-out, obtains product, yield 64%.

LC/MS(m/z)：415(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.65-1.75(m，4H)，1.84-1.90(m，4H)，1.97(s，3H)，2.37(s，3H)，2.84(t，2H)，3.58(t，2H)，3.70-3.80(m，1H)，6.54(s，1H)，7.34(d，1H)，7.70(s，1H)，8.45(br，1H)，11.65(br，1H).

Embodiment 252

N-(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-Toluidrin

Under 0 ℃, to 1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.05g, 0.13mmol) 10mL DCM solution add methylsulfonyl chloride (0.02g, 0.13mmol) succeeded by pyridine (0.02g, 0.21mmol).Reactant stirred at ambient temperature spend the night, concentrate, through the flash chromatography on silica gel purifying, with 20-50%EtOAc/ hexane wash-out, obtain product, be white solid, yield 75%.

LC/MS(m/z)：451(M+1) ⁺； ¹H?NMR(400MHz，DMSO)δ1.62-1.76(m，4H)，1.82-1.92(m，4H)，2.32(s，3H)，2.75(t，2H)，2.84(s，3H)，3.80-3.90(m，1H)，4.10(t，2H)，6.76(s，1H)，7.37(d，1H)，7.83(s，1H)，8.16(d，1H)，10.64(br，1H)，11.80(br，1H).

Embodiment 253

N-(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-2-dimethylamino ethanamide

N-(2-{-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-2-dimethylamino ethanamide (37mg, 61%) be from 1-[4-(amino-ethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (0.05g, 0.13mmol), (0.02g is 0.13mmol) according to common processes K preparation for dimethylamino acetic acid.

LC/MS(m/z)：458(M+1) ⁺； ¹H?NMR(400MHz，CD ₃OD)δ1.63-1.70(m，4H)，1.80-1.95(m，4H)，2.36(s，3H)，2.70(s，6H)，2.85(t，2H)，3.60(t，2H)，3.62(s，2H)，3.86(br，1H)，6.65(s，1H)，7.38-7.28(m，2H)，7.65-7.74(m，1H)，7.80(br，1H)，8.20(br，1H)，

Embodiment 254

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl)-succinamic acid

Make 1-[4-(amino-methyl)-thiazol-2-yl]-(0.10g is 0.28mmol) with succinyl oxide (0.08g, 10mLDCM solution backflow 2h 0.78mmol) for 3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.The concentration response thing, purifying on silica gel is used the 5%MeOH/EtOAc wash-out, obtains required product (77mg, 60%).

LC/MS(m/z)：459(M+1) ⁺； ¹H?NMR(400MHz，CD ₃OD)δ1.70-1.77(m，4H)，1.85-1.95(m，4H)，2.39(s，3H)，2.62-2.72(m，4H)，3.71(s，2H)，3.80-3.90(m，1H)，6.08(s，1H)，7.40-(d，1H)，7.75(s，1H)，8.70(d，1H)，11.30(s，1H)，

Embodiment 255

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the vinylformic acid ethyl ester

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-vinylformic acid ethyl ester (70mg, 58%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(1-oxo-methyl)-thiazol-2-yl]-urea (0.10g, 0.28mmol) and (ethoxycarbonyl methylene radical)-triphenyl phosphine (0.12g is 0.34mmol) according to common processes X preparation.

LC/MS(m/z)：428(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.29(t，3H)，1.67-1.75(m，4H)，1.80-1.95(m，4H)，2.37(s，3H)，3.70-3.80(m，1H)，4.19-4.22(q，2H)，6.56(d，1H)，7.07(s，1H)，7.36(d，1H)，7.50(d，1H)，7.72(s，1H)，8.45(d，1H)，

Embodiment 256

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the propionic acid ethyl ester

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-propionic acid ethyl ester (48mg, 96%) be from 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-(0.05g is 0.12mmol) with the preparation of the hydrogenization of Pd/C for the vinylformic acid ethyl ester.

LC/MS(m/z)：430(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.22(t，3H)，1.64-1.70(m，4H)，1.80-1.95(m，4H)，2.35(s，3H)，2.69(t，2H)，2.98(t，2H)，3.67-3.80(m，1H)，4.01-4.15(q，2H)，6.50(s，1H)，7.32(d，1H)，7.68(s，1H)，8.45(br，1H)，11.60(br，1H).

Embodiment 257

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-propionic acid

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-propionic acid (15mg, 88%) be from 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl-the propionic acid ethyl ester (0.03g, 0.04mmol) and 2.5M LiOH (20mL) according to common processes J preparation.

LC/MS(m/z)：402(M+1) ⁺； ¹H?NMR(400MHz，CD ₃OD)δ1.70-1.80(m，4H)，1.82-1.95(m，4H)，2.34(s，3H)，2.58(t，2H)，2.80(t，2H)，3.82-3.94(m，1H)，6.69(s，1H)，7.38(d，1H)，7.85(s，1H)，8.19(br，1H)，10.65(br，1H).

Embodiment 258

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-but-2-ene acid ethyl ester

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-but-2-ene acid ethyl ester (50mg, 42%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(2-oxo-ethyl)-thiazol-2-yl]-urea (0.10g, 0.27mmol) and (ethoxycarbonyl methylene radical)-triphenyl phosphine (0.09g is 0.27mmol) according to common processes X preparation.

LC/MS(m/z)：442(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.28(t，3H)，1.67-1.73(m，4H)，2.37(s，3H)，3.56(d，1H)，3.70-3.80(m，1H)，4.15-4.21(q，2H)，5.88(d，1H)，6.55(s，1H)，7.37(d，1H)，7.65(s，1H)，8.43(br，1H)，11.65(br，1H).

Embodiment 259

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(1H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(1H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-urea (76mg, 69%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 442 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.76 (m, 4H), 1.92 (m, 4H), 2.32 (s, 3H), 3.88 (p, 1H), 4.43 (s, 2H), 6.94 (s, 1H), 7.11 (d, 1H), 7.36 (d, 1H), 7.88 (d, 1H), 7.71 (s, 1H), 8.52 (d, 1H), 10.34 (br, 2H) and 11.42 (br, 1H).

Embodiment 260

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl methyl)-thiazol-2-yl]-urea (93mg, 79%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 458 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.73 (m, 4H), 1.88 (m, 4H), 2.37 (s, 3H), 3.76 (p, 1H), 3.86 (s, 3H), 4.55 (s, 2H), 6.88 (s, 1H), 7.34 (d, 1H), 7.70 (s, 1H), 8.40 (d, 1H), 8.52 (br, 1H) and 11.78 (br, 1H).

Embodiment 261

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-base sulfenyl methyl)-thiazol-2-yl]-urea (106mg, 86%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 494 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.66 (m, 4H), 1.84 (m, 4H), 2.21 (s, 3H), 3.72 (p, 1H), 4.29 (s, 2H), 4.63 (br, 1H), 6.78 (s, 1H), 7.11 (s, 1H), 7.28 (d, 1H), 7.75 (s, 1H), 8.13 (s, 1H), 8.42 (d, 1H), 9.24 (br, 1H) and 11.40 (br, 1H).

Embodiment 262

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-alkylsulfonyl methyl)-thiazol-2-yl]-urea (78mg; 74%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(9H-purine-6-base sulfenyl methyl)-thiazol-2-yl]-urea (99mg; 0.20mmol) according to common processes R preparation, obtain title compound.

LC-MS (m/z): 526 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.58 (m, 4H), 1.66 (m, 2H), 1.74 (m, 2H), 2.32 (s, 3H), 3.74 (p, 1H), 4.58 (s, 2H), 6.71 (d, 1H), 7.06 (d, 1H), 7.16 (s, 1H), 7.42 (d, 1H), 7.72 (br, 1H), 8.18 (d, 1H), 8.98 (s, 1H), 9.88 (br, 1H) and 10.26 (br, 1H).

Embodiment 263

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-urea (79mg, 70%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 453 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.68 (m, 4H), 1.86 (m, 4H), 2.36 (s, 3H), 3.76 (p, 1H), 4.21 (s, 2H), 6.78 (s, 1H), 7.16-7.20 (dd, 2H), 7.34 (d, 1H), 7.70 (s, 1H), 8.13 (s, 1H), 8.38 (dd, 1H), 8.42 (d, 1H), 9.46 (br, 1H) and 11.70 (br, 1H).

Embodiment 264

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(pyridine-4-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(pyridine-4-alkylsulfonyl methyl)-thiazol-2-yl]-urea (73mg; 75%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-(90mg 0.20mmol) prepares according to common processes R urea.

LC-MS (m/z): 485 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.66 (m, 4H), 1.86 (m, 4H), 2.37 (s, 3H), 3.78 (p, 1H), 4.49 (s, 2H), 6.88 (s, 1H), 7.36 (d, 1H), 7.62 (dd, 2H), 7.72 (s, 1H), 8.42 (d, 1H), 8.86 (d, 2H), 9.40 (br, 1H) and 11.52 (br, 1H).

Embodiment 265

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-tetrazolium-1-yl)-acetic acid

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-tetrazolium-1-yl)-acetic acid (100mg, 80%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 501 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.74 (m, 4H), 1.90 (m, 4H), 2.33 (s, 3H), 3.72 (p, 1H), 4.22 (s, 2H), 5.00 (s, 2H), 6.92 (s, 1H), 7.52 (d, 1H), 7.72 (s, 1H), 8.38 (d, 1H), 9.82 (br, 1H), 10.32 (br, 1H) and 11.70 (br, 1H).

Embodiment 266

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-4-cyclopropyl-4H-[1,2,4] triazole-3-ylmethyl)-the carboxylamine tertiary butyl ester

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-4-cyclopropyl-4H-[1,2,4] triazole-3-ylmethyl)-carboxylamine tertiary butyl ester (136mg, 89%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 612 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.04 (m, 2H), 1.14 (m, 2H), 1.40 (s, 9H), 1.66 (m, 4H), 1.84 (m, 4H), 2.35 (s, 3H), 2.88 (p, 1H), 3.70 (p, 1H), 4.52 (s, 2H), 4.54 (s, 2H), 5.78 (br, 1H), 6.80 (s, 1H), 7.34 (d, 1H), 7.66 (s, 1H), 8.32 (d, 1H), 10.24 (br, 1H) and 11.36 (br, 1H).

Embodiment 267

1-[4-(5-amino methyl-4-cyclopropyl-4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea hydrochloride

1-[4-(5-amino methyl-4-cyclopropyl-4 H-[1; 2; 4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (51mg; 99%) be from (5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol-4-cyclopropyl-4H-[1; 2; 4] triazole-3-ylmethyl)-the carboxylamine tertiary butyl ester (61mg, 0.10mmol) and hydrochloric acid (4mL, the 4.0M solution in two _ alkane) go to protect prepared according to general.

LC-MS (m/z): 512 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.24 (m, 2H), 1.38 (m, 2H), 1.72 (m, 4H), 1.94 (m, 4H), 2.38 (s, 3H), 2.92 (p, 1H), 3.65 (s, 2H), 3.77 (s, 2H), 4.08 (m, 1H), 5.24 (br, 2H), 6.90 (s, 1H), 7.52 (d, 1H), 7.72 (s, 1H), 8.42 (d, 1H), 10.24 (br, 1H) and 11.36 (br, 1H).

Embodiment 268

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-1H-imidazoles-4-carboxylic acid ethyl ester

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-1H-imidazoles-4-carboxylic acid ethyl ester (112mg, 88%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 486 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.36 (t, 3H), 1.74 (m, 4H), 1.90 (m, 4H), 2.36 (s, 3H), 3.78 (p, 1H), 4.08 (q, 2H), 4.34 (s, 2H), 6.84 (s, 1H), 7.34 (d, 1H), 7.72 (d, 1H), 7.88 (d, 1H), 8.18 (d, 1H), 8.38 (d, 1H), 10.24 (br, 1H) and 11.88 (br, 1H).

Embodiment 269

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-1H-imidazoles-4-carboxylic acid (91mg, 94%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-(102mg 0.20mmol) prepares according to common processes J 1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS (m/z): 474 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.74 (m, 4H), 1.92 (m, 4H), 2.34 (s, 3H), 3.87 (p, 1H), 4.37 (s, 2H), 6.89 (s, 1H), 7.39 (d, 1H), 7.68 (d, 1H), 7.84 (d, 1H), 8.15 (d, 1H), 8.26 (d, 1H), 9.28 (br, 1H), 10.66 (br, 1H) and 11.90 (br, 1H).

Embodiment 270

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid ethyl ester

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid ethyl ester (35mg; 64%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-(51mg 0.10mmol) prepares according to common processes R 1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS (m/z): 546 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.42 (t, 3H), 1.63 (m, 4H), 1.76 (m, 2H), 1.88 (m, 2H), 2.34 (s, 3H), 3.88 (p, 1H), 4.12 (q, 2H), 4.82 (s, 2H), 6.94 (s, 1H), 7.38 (d, 1H), 7.55 (d, 1H), 7.72 (d, 1H), 7.91 (d, 1H), 6 (d, 1H), 9.78 (br, 1H) and 11.90 (br, 1H).

Embodiment 271

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid (43mg; 83%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-base methylsulfonyl }-(52mg 0.10mmol) prepares according to common processes J 1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS (m/z): 518 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.63 (m, 4H), 1.74 (m, 2H), 1.86 (m, 2H), 2.34 (s, 3H), 3.85 (p, 1H), 4.82 (s, 2H), 6.92 (s, 1H), 7.38 (d, 1H), 7.54 (d, 1H), 7.72 (d, 1H), 7.90 (s, 1H), 7.96 (br, 1H), 8.22 (d, 1H), 10.58 (br, 1H) and 11.88 (br, 1H).

Embodiment 272

4-amino-2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-pyrimidine-5-carboxylic acid's ethyl ester

4-amino-2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-pyrimidine-5-carboxylic acid's ethyl ester (113mg, 84%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 541 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.34 (t, 3H), 1.72 (m, 4H), 1.88 (m, 4H), 2.34 (s, 3H), 3.62 (br, 2H), 3.74 (p, 1H), 4.10 (q, 2H), 4.36 (s, 2H), 6.90 (s, 1H), 7.36 (d, 1H), 7.74 (d, 1H), 8.18 (dd, 1H), 8.56 (s, 1H), 10.12 (br, 1H) and 11.78 (br, 1H).

Embodiment 273

4-amino-2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-pyrimidine-5-carboxylic acid

4-amino-2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-pyrimidine-5-carboxylic acid (94mg, 91%) be from 4-amino-2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-(108mg 0.20mmol) prepares according to common processes J pyrimidine-5-carboxylic acid's ethyl ester.

LC-MS (m/z): 513 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.72 (m, 4H), 1.88 (m, 4H), 2.34 (s, 3H), 3.66 (br, 2H), 3.86 (p, 1H), 4.36 (s, 2H), 7.07 (s, 1H), 7.32 (d, 1H), 7.72 (d, 1H), 8.20 (dd, 1H), 8.56 (s, 1H), 9.76 (br, 1H), 10.64 (br, 1H) and 11.74 (br, 1H).

Embodiment 274

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-4-hydroxyl-pyrimidine-5-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-4-hydroxyl-pyrimidine-5-carboxylic acid (104mg, 81%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-(135mg 0.25mmol) prepares according to common processes J 4-hydroxyl-pyrimidine-5-carboxylic acid's ethyl ester.

LC-MS (m/z): 514 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 1.74 (m, 4H), 1.90 (m, 4H), 2.36 (s, 3H), 3.84 (p, 1H), 4.28 (s, 2H), 6.98 (s, 1H), 7.36 (d, 1H), 7.70 (d, 1H), 8.36 (dd, 1H), 8.56 (s, 1H), 9.04 (br, 1H), 9.76 (br, 1H), 10.64 (br, 1H) and 11.74 (br, 1H).

Embodiment 275

1-[4-(5-amino-thiazolyl--2-base sulfenyl methyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-[4-(5-amino-thiazolyl--2-base sulfenyl methyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (96mg, 81%) be that (94mg 0.25mmol) prepares according to common processes Q from 1-(4-chloromethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea.

LC-MS (m/z): 474 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.68 (m, 4H), 1.84 (m, 4H), 2.37 (s, 3H), 3.72 (p, 1H), 4.34 (s, 2H), 5.18 (br, 2H), 6.58 (s, 1H), 7.16 (s, 1H), 7.36 (d, 1H), 7.64 (s, 1H), 8.26 (d, 1H), 10.56 (br, 1H) and 11.60 (br, 1H).

Embodiment 276

2-[3-(2-pentamethylene carbonyl-5-methanesulfonamido-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(2-pentamethylene carbonyl-5-methanesulfonamido-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (102mg, 80%) be from N-(5-amino-4-pentamethylene carbonyl-2-methyl-phenyl)-Toluidrin (198mg, 0.5mmol) and ethyl 2-amino-4-thiazolyl acetate (93mg is 0.5mmol) according to common processes D preparation.

LC-MS (m/z): 509 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.27 (t, 3H), 1.70 (m, 4H), 1.88 (m, 4H), 2.29 (s, 3H), 3.30 (s, 2H), 3.68 (s, 3H), 4.19 (q, 2H), 4.24 (p, 1H), 6.48 (s, 1H), 6.72 (s, 1H), 7.74 (s, 1H), 8.64 (br, 1H), 9.62 (br, 1H) and 11.82 (br, 1H).

Embodiment 277

2-[3-(2-pentamethylene carbonyl-5-methanesulfonamido-4-methyl-phenyl)-urea groups]-thiazole-4-yl)-acetic acid

2-[3-(2-pentamethylene carbonyl-5-methanesulfonamido-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (116mg, 97%) be that (127mg is 0.25mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-5-methanesulfonamido-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS (m/z): 481 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.68 (m, 4H), 1.84 (m, 4H), 2.38 (s, 3H), 3.03 (s, 3H), 3.64 (s, 2H), 4.24 (p, 1H), 5.36 (br, 1H), 6.50 (s, 1H), 6.78 (s, 1H), 7.68 (s, 1H), 9.62 (br, 1H), 11.24 (br, 1H) and 12.54 (br, 1H).

Embodiment 278

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(1H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(1H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea (25mg, 50%) be from methylsulfonic acid 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl ester (0.05g, 0.11mmol) and 1H-imidazoles-2-mercaptan (0.009g is 0.11mmol) according to common processes Z preparation.

LC/MS(m/z)：456(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)？1.63-1.68(m，4H)，1.83-1.88(m，4H)，2.35(s，3H)，2.87-2.93(m，2H)，3.25-3.28(m，2H)，3.60-3.75(m，1H)，6.74(s，1H)，6.85-7.10(m，2H)，7.33(d，1H)，7.65(s，1H)，8.4(d，1H)，11.35(br，1H).

Embodiment 279

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea (45mg, 43%) be from methylsulfonic acid 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl ester (0.10g, 0.22mmol) and 1-methyl isophthalic acid H-imidazoles-2-mercaptan (0.04g is 0.33mmol) according to common processes Z preparation.

LC/MS(m/z)：470(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.73-1.76(m，4H)，1.90-1.93(m，4H)，2.36(s，3H)，3.04(t，2H)，3.35(t，2H)，3.63(s，3H)，3.65-3.80(m，1H)，6.51(s，1H)，6.71(d，2H)，7.33(d，1H)，7.68(s，1H)，8.40(br，1H)，11.43(br，1H).

Embodiment 280

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridine-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridine-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea (24mg, 467%) be from methylsulfonic acid 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl ester (0.05g, 0.11mmol) and the 2-mercaptopyridine (0.012g is 0.11mmol) according to common processes Z preparation.

LC/MS(m/z)：467(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)？1.62-1.74(m，4H)，1.85-1.93(m，4H)，2.36(s，3H)，3.05(t，2H)，3.50(t，2H)，3.72-3.80(m，1H)，6.54(s，1H)，7.13-7.10(m，2H)，7.60-7.65(m，3H)，8.46-8.49(m，2H)，11.72(br，1H).

Embodiment 281

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-yl sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{4-[2-(pyridin-4-yl sulfenyl)-ethyl]-thiazol-2-yl }-urea (74mg, 60%) be from methylsulfonic acid 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethyl ester (0.12g, 0.27mmol) and the 2-mercaptopyridine (0.04g is 0.39mmol) according to common processes Z preparation.

LC/MS(m/z)：467(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)δ1.69-1.73(m，4H)，1.87-1.92(m，4H)，2.37(s，3H)，3.03(t，2H)，3.34(t，2H)，3.75-3.79(m，1H)，6.58(s，1H)，7.16(d，2H)，7.25(d，2H)，7.36(d，1H)，7.71(s，1H)，8.46(d，1H)，11.74(s，1H).

Embodiment 282

3-{2-[3-(2-ethanoyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-propionic acid

3-(2-amino-thiazolyl--4-methylthiol)-propionic acid methyl ester (0.75g, 60%) is that (1.00g, 5.41mmol) (0.97g 8.11mmol) prepares according to technology Z with 3-sulfydryl-propionic acid methyl ester from 4-chloromethyl-thiazol-2-yl amine.

3-{2-[3-(2-ethanoyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-propionic acid methyl ester (0.28g; 61%) be from 3-(2-amino-thiazolyl--4-methylthiol)-propionic acid methyl ester (0.23g; 0.99mmol) and (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (0.24g; 1.49mmol), prepare according to technology D.

3-{2-[3-(preparation of 2-ethanoyl-4-methyl-phenyl)-urea groups]-thiazole-4-methylthiol }-propionic acid (40mg; 83%) be from [4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } oxyethyl group)-phenyl] the acetic acid methyl ester (0.05g, 0.11mmol) and 2.5M LiOH (20uL) according to common processes J preparation.

LC/MS(m/z)：448(M+1) ⁺； ¹H?NMR(400MHz，DMSO)？1.70-1.80(m，4H)，1.85-1.97(m，4H)，2.28(s，3H)，2.67(t，2H)，2.83(t，2H)，3.70(s，2H)，3.85-3.90(m，1H)，6.89(s，1H)，7.20(d，2H)，7.85(s，1H)，8.20(d，1H)，10.64(br，1H)，10.73(br，1H)，12.14(br，1H).

Embodiment 283

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea (94mg, 25%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) and sodium methyl mercaptide (140mg is 2mmol) according to common processes Q preparation.

LC-MS(m/z)：376(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.74(m，4H)，1.93(m，4H)2.38(s，3H)，2.43(s，3H)，3.79(m，1H)，7.37(d，1H)，7.73(s，2H)，8.45(d，1H)，11.65(br，1H)，12.20(br，1H).

Embodiment 284

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-the acetic acid methyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-acetic acid methyl ester (130mg, 30%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) and sulfydryl-acetic acid methyl ester (212mg is 2mmol) according to common processes Q preparation.

LC-MS(m/z)：434(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.91(m，4H)，2.38(s，3H)，3.47(s，3H)，3.72(s，3H)，3.79(m，1H)，7.39(d，1H)，7.75(d，2H)，8.43(d，1H)，11.40(br，1H)，11.66(br，1H).

Embodiment 285

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-acetic acid (161mg, 75%) be that (229mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-acetic acid methyl ester.

LC-MS(m/z)：420(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.61(m，4H)，1.74(m，2H)，1.89(m，2H)，2.33(s，3H)，3.49(s，3H)，3.88(m，1H)，7.41(d，2H)，7.92(d，1H)，8.33(d，1H)，10.80(br，1H)，10.98(br，1H)，12.12(br，1H).

Embodiment 286

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-the acetic acid methyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-acetic acid methyl ester (175mg; 75%) be that (217mg is 0.5mmol) by carrying out oxygenizement according to common processes R preparation with m-cpba from { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-sulfenyl }-acetic acid methyl ester.

LC-MS(m/z)：466(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.91(m，4H)，2.38(s，3H)，3.78(m，4H)，4.24(s，2H)，7.41(d，1H)，7.77(s，1H)，8.30(s，1H)，8.42(d，1H)，11.89(br，1H).

Embodiment 287

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-acetic acid (158mg; 70%) be that (233mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-acetic acid methyl ester.

LC-MS (m/z): 452 (M+1) ^{+ 1}H NMR (400MHz, acetone-d ₆): δ 1.67 (m, 4H) .1.71 (m, 4H), 1.91 (m, 4H), 2.38 (s, 3H), 3.95 (m, 1H), 4.44 (s, 2H), 7.44 (d, 1H), 7.97 (s, 2H), 8.42 (d, 1H), 11.15 (br, 1H), 11.35 (br, 1H).

Embodiment 288

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-the propionic acid methyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid methyl ester (125mg, 28%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) and sulfydryl-propionic acid methyl ester (240mg is 2mmol) according to common processes Q preparation.

LC-MS(m/z)：448(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.91(m，4H)，2.38(s，3H)，2.65(s，2H)，3.51(s，2H)，3.66(s，3H)，3.78(m，1H)，6.90(d，1H)，7.38(d，1H)，7.73(s，1H)，8.42(d，1H)11.62(br，1H)，11.65(br，1H).

Embodiment 289

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid (138mg, 72%) be that (217mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid methyl ester.

LC-MS(m/z)：433(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.67(m，4H)，1.89(m，4H)，2.36(s，3H)，2.51(s，2H)，3.59(s，2H)，3.78(m，1H)，6.90(d，1H)，7.41(d，1H)，7.93(s，1H)，8.45(d，1H)，9.56(br，1H)，11.16(br，1H)，11.25(br，1H).

Embodiment 290

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-the propionic acid methyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-propionic acid methyl ester (163mg; 68%) be that (224mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation from { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-sulfenyl }-propionic acid methyl ester.

LC-MS(m/z)：480(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，6H)，1.91(m，2H)，2.40(s，3H)，2.85(m，2H)，3.56(m，2H)，3.67(s，3H)，3.81(m，1H)，7.41(dd，1H)，7.78(s，2H)，8.29(s，1H)，8.42(d，1H)，11.40(br，1H)，11.91(br，1H).

Embodiment 291

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-propionic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-propionic acid (168mg; 72%) be that (240mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-propionic acid methyl ester.

LC-MS(m/z)：466(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.91(m，4H)，2.38(s，3H)，2.89?(s，2H)，3.63(s，2H)，3.81(m，1H)，7.39(d，1H)，7.75(d，2H)，8.43(d，1H)，11.40(br，1H)，11.66(br，1H).

Embodiment 292

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base-sulfenyl }-ethyl)-ethanamide

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base-sulfenyl }-ethyl)-ethanamide (156mg, 35%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) and N-(2-sulfydryl-ethyl)-ethanamide (240mg is 2mmol) according to common processes Q preparation.

LC-MS(m/z)：447(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.91(m，4H)，1.99(s，3H)，2.38(s，3H)，2.85(t，3H)，3.46(q，2H)，3.79(m，1H)，5.95(br，1H)，7.37(d，1H)，7.69(d，2H)，8.42(d，1H)，11.35(br，1H)，11.57(br，1H).

Embodiment 293

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base-alkylsulfonyl }-ethyl)-ethanamide

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base-alkylsulfonyl }-ethyl)-ethanamide (167mg; 70%) be from N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base-sulfenyl-ethyl)-(223mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for ethanamide.

LC-MS(m/z)：479(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.70(m，4H)，1.92(m，4H)，2.01(s，3H)，2.39(s，3H)，3.42(m，2H)，3.76(m，3H)，6.32(m，1H)，7.39(d，1H)，7.76(s，2H)，8.13(s，1H)，8.40(d，1H)，11.66(br，1H).

Embodiment 294

2-acetylaminohydroxyphenylarsonic acid 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-the propionic acid methyl ester

2-acetylaminohydroxyphenylarsonic acid 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid methyl ester (156mg, 35%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (354mg 2mmol) prepares according to common processes Q with 2-acetylaminohydroxyphenylarsonic acid 3-sulfydryl-propionic acid methyl ester.

LC-MS(m/z)：505(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，6H)，1.91(m，2H)，2.03(s，3H)，2.38(s，3H)，3.24(m，2H)，3.66(s，3H)，3.79(m，1H)，4.84(m，1H)，6.42(d，1H)，7.39，d，1H)，7.60(s，1H)，7.73(s，1H)，8.43(d，1H)，10.88(br，1H)，11.64(br，1H).

Embodiment 295

2-acetylaminohydroxyphenylarsonic acid 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid

2-acetylaminohydroxyphenylarsonic acid 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid (187mg, 76%) be from 2-acetylaminohydroxyphenylarsonic acid 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(245mg 0.5mmol) prepares according to common processes J the propionic acid methyl ester.

LC-MS (m/z): 491 (M+1) ^{+ 1}H NMR (400MHz, acetone-d ₆): δ 1.68 (m, 4H), 1.84 (m, 4H), 1.97 (s, 3H), 2.37 (s, 3H), 3.10 (m, 1H), 3.26 (m, 1H), 3.94 (m, 1H), 4.64 (m, 1H), 5.8 (br, 1H), 7.45 (d, 1H), 7.54 (d, 1H), 8.01 (s, 1H), 8.43 (d, 1H), 11.20 (br, 1H), 11.44 (br, 1H).

Embodiment 296

2-t-butoxycarbonyl amino-3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups] thiazole-5-base sulfenyl }-the propionic acid methyl ester

2-t-butoxycarbonyl amino-3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups] thiazole-5-base sulfenyl }-propionic acid methyl ester (196mg, 35%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (470mg 2mmol) prepares according to common processes Q with 2-t-butoxycarbonyl amino-3-sulfydryl-propionic acid methyl ester.

LC-MS(m/z)：563(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.55(s，9H)，1.71(m，4H)，1.91(m，4H)，2.37(s，3H)，3.18(m，2H)，3.76(m，4H)，4.53(m，1H)，5.45(m，1H)，7.35(d，1H)，7.65(s，1H)，7.72(s，1H)，8.43(d，1H)，11.60(br，1H)，11.66(br，1H).

Embodiment 297

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-ethyl)-the carboxylamine tertiary butyl ester

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-ethyl)-carboxylamine tertiary butyl ester (202mg, 40%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (354mg 2mmol) prepares according to common processes Q with (2-sulfydryl-ethyl)-carboxylamine tertiary butyl ester.

LC-MS(m/z)：505(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.45(s，9H)，1.71(m，4H)，1.92(m，4H)，2.38(s，3H)，2.83(m，2H)，3.32(m，2H)，3.78(m，1H)，4.95(br，1H)，7.36(d，1H)，7.73(s，2H)，8.43(d，1H)，11.48(br，1H)，11.62(br，1H).

Embodiment 298

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-ethyl-ammonium chloride

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-ethyl-ammonium chloride (183mg, 90%) be to prepare like this, even (2-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-ethyl)-(253mg is 0.5mmol) with two _ alkane solution reaction of 4N HCl for the carboxylamine tertiary butyl ester.

LC-MS(m/z)：406(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.63(m，4H)，1.73(m，2H)，1.91(m，2H)，2.33(s，3H)，2.91(m，2H)，3.18(m，2H)，3.87(m，1H)，7.39(d，1H)，7.56(s，2H)，7.85(s，1H)，8.16(d，1H)，10.71(br，1H)，12.20(br，1H).

Embodiment 299

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-ethyl) the carboxylamine tertiary butyl ester

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-ethyl)-carboxylamine tertiary butyl ester (195mg; 73%) be from (2-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-sulfenyl-ethyl) (252mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for the carboxylamine tertiary butyl ester.

LC-MS(m/z)：537(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.44(s，9H)，1.71(m，4H)，1.91(m，4H)，2.38(s，3H)，3.46(t，2H)，3.78(m，3H)，3.81(m，1H)，7.39(d，1H)，7.75(d，2H)，8.43(d，1H)，11.40(br，1H)，11.66(br，1H).

Embodiment 300

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-ethyl ammonium chloride

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-ethyl-ammonium chloride (185mg; 85%) be to prepare like this; even (2-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-ethyl)-(253mg is 0.5mmol) with two _ alkane solution reaction of 4N HCl for the carboxylamine tertiary butyl ester.

LC-MS(m/z)：438(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.61(m，4H)，1.72(m，2H)，1.88(m，2H)，2.34(s，3H)，3.01(br，2H)，3.70(t，2H)，3.88(m，1H)，7.41(d，1H)，7.87(s，1H)，8.13(d，1H)，8.15(br，1H)，10.75(br，1H)，11.62(br，1H).

Embodiment 301

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-dimethylamino-ethylmercapto group)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-dimethylamino-ethylmercapto group)-thiazol-2-yl]-urea (130mg, 30%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (210mg 2mmol) prepares according to common processes Q with 2-dimethylamino-sulfur alcohol.

LC-MS(m/z)：433(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.92(m，4H)，2.24(s，6H)，2.38(s，3H)，2.55(m，2H)，2.83(m，2H)，3.78(m，1H)，7.36(d，1H)，7.69(s，1H)，7.74(s，1H)，8.44(d，1H)，11.65(br，1H).

Embodiment 302

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-hydroxyl-ethylmercapto group)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-hydroxyl-ethylmercapto group)-thiazol-2-yl]-urea (114mg, 28%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (158mg 2mmol) prepares according to common processes Q with 2-hydroxyl-sulfur alcohol.

LC-MS (m/z): 406 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃/ acetone-d ₆): δ 1.52 (m, 4H), 1.68 (m, 2H), 1.75 (m, 2H), 2.33 (s, 3H), 2.71 (t, 3H), 3.58 (m, 2H), 3.90 (m, 1H), 7.17 (d, 1H), 7.31 (s, 1H), 7.56 (s, 1H), 8.27 (d, 1H), 11.20 (br, 1H).

Embodiment 303

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-hydroxyl-ethylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-hydroxyl-ethylsulfonyl)-thiazol-2-yl]-urea (153; 70%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-hydroxyl-ethylmercapto group)-thiazol-2-yl]-(204mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for urea.

LC-MS (m/z): 438 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃/ acetone-d ₆): δ 1.66 (m, 4H), 1.89 (m, 4H), 2.37 (s, 3H), 3.48 (m, 2H), 3.72 (m, 2H), 4.07 (m, 2H), 7.37 (d, 1H), 7.54 (d, 1H), 7.66 (d, 1H), 8.01 (d, 1H), 11.88 (br, 1H).

Embodiment 304

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea (140mg, 32%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (222mg 2mmol) prepares according to common processes Q with the 2-mercaptopyridine.

LC-MS(m/z)：439(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.63(m，4H)，1.86(m，4H)，2.37(s，3H)，3.76(m，1H)，7.04(m，2H)，7.37(d，1H)，7.51(m，1H)，7.73(s，1H)，7.92(s，1H)，8.42(d，1H)，8.48(d，1H)，11.16(br，1H)，11.81(br，1H).

Embodiment 305

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea (176mg; 75%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfenyl)-thiazol-2-yl]-(219mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for urea.

LC-MS(m/z)：471(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.68(m，4H)，1.93(m，4H)，2.39(s，3H)，3.79(m，1H)，7.39(d，1H)，7.48(m，1H)，7.76(s，1H)，7.93(dd，1H)，8.15(d，1H)，8.33(br，1H)，8.42(d，1H)，8.70(d，1H)，10.8(br，1H)，11.93(br，1H).

Embodiment 306

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-base sulfenyl)-thiazol-2-yl]-urea (142mg, 32%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (222mg 2mmol) prepares according to common processes Q with the 2-mercaptopyrimidine.

LC-MS(m/z)：440(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.64(m，4H)，1.89(m，4H)，2.36(s，3H)，3.81(m，1H)，7.01(t，1H)，7.34(d，2H)，7.72(s，1H)，7.87(s，1H)，8.47(d，1H)，8.58(d，1H)，8.67(d，1H)，11.70(br，1H)，11.78(br，1H).

Embodiment 307

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-base alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-alkylsulfonyl)-thiazol-2-yl]-urea (169mg; 72%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyrimidine-2-sulfenyl)-thiazol-2-yl]-(220mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for urea.

LC-MS(m/z)：472(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.71(m，4H)，1.91(m，4H)，2.38(s，3H)，3.78(m，1H)，7.39(d，1H)，7.49(t，1H)，7.76(s，1H)，8.31(s，1H)，8.43(d，1H)，8.93(d，2H)，11.80(br，1H)，11.94(br，1H).

Embodiment 308

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-yl sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-yl sulfenyl)-thiazol-2-yl]-urea (110mg, 25%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (222mg 2mmol) prepares according to common processes Q with the 4-mercaptopyridine.

LC-MS(m/z)：439(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.62(m，4H)，1.84(m，4H)，2.35(s，3H)，3.73(m，1H)，7.10(d，2H)，7.34(d，2H)，7.71(s，1H)，7.95(s，1H)，8.38(d，1H)，8.42(d，1H)，11.65(br，1H)，11.75(br，1H).

Embodiment 309

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea (141mg, 32%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (228mg 2mmol) prepares according to common processes Q with 1-methyl isophthalic acid H-imidazoles-2-mercaptan.

LC-MS(m/z)：442(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.66(m，4H)，1.88(m，4H)，2.35(s，3H)，3.74(m，1H)，3.77(s，3H)，6.93(s，1H)，7.06(s，1H)，7.32(d，1H)，7.69(s，1H)，7.82(s，1H)，8.40(d，1H)，11.51(br，1H)，12.20(br，1H).

Embodiment 310

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea (149mg, 35%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (200mg 2mmol) prepares according to common processes Q with 1H-imidazoles-2-mercaptan.

LC-MS(m/z)：428(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.70(m，4H)，1.91(m，4H)，2.37(s，3H)，3.83(m，1H)，7.10(s，1H)，7.34(d，1H)，7.57(s，2H)，7.66(s，1H)，7.78(s，1H)，8.42(d，1H)，11.22(br，1H).

Embodiment 311

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(7H-purine-6-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(7H-purine-6-base sulfenyl)-thiazol-2-yl]-urea (124mg, 28%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (304mg 2mmol) prepares according to common processes Q with 7H-purine-6-mercaptan.

LC-MS(m/z)：480(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.61(m，4H)，1.81(m，4H)，2.26(s，3H)，3.64(m，1H)，7.21d，2H)，7.54(d，2H)，8.02(s，1H)，8.26(d，1H)，8.56(s，1H)，11.12(br，1H)，11.62(br，1H).

Embodiment 312

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-the nicotinic acid methyl ester

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid methyl ester (124mg, 25%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (340mg 2mmol) prepares according to common processes Q with 2-sulfydryl-nicotinic acid methyl ester.

LC-MS(m/z)：497(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.64(m，4H)，1.85(m，4H)，2.36(s，3H)，3.74(m，1H)，3.98(s，3H)，7.08(dd，1H)，7.34?(d，2H)，7.71(s，1H)，7.79(s?1H)，8.22(dd，1H)，8.45(d，1H)，8.49(dd，1H)，11.45(br，1H)，11.75(br，1H).

Embodiment 313

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid (186mg, 75%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(248mg 0.5mmol) prepares according to common processes J the nicotinic acid methyl ester.

LC-MS(m/z)：483(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.62(m，4H)，1.75(m，2H)，1.89(m，2H)，2.33(s，3H)，3.88(m，1H)，7.23(dd，1H)，7.39(d，1H)，7.47(s，1H)，7.86(s，1H)，8.19(m，2H)，8.24(dd，1H)，10.70(br，1H)，12.23(br，1H)

Embodiment 314

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-the nicotinic acid methyl ester

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-nicotinic acid methyl ester (185mg; 70%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(248mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for the nicotinic acid methyl ester.

LC-MS(m/z)：529(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ1.68(m，4H)，1.85(m，2H)，1.95(m，2H)，2.38(s，3H)，3.95(m，1H)，3.99(s，3H)，7.42(d，1H)，7.79(dd，2H)，7.97(s，1H)，8.14(s，1H)，8.15(d，1H)，8.82(d，1H)，8.79(d，1H)，11.35(br，1H)，11.68(br，1H).

Embodiment 315

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-nicotinic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-nicotinic acid (200mg; 78%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-(264mg 0.5mmol) prepares according to common processes J the nicotinic acid methyl ester.

LC-MS (m/z): 515 (M+1) ^{+ 1}H NMR (400MHz, acetone-d ₆): δ 1.67 (m, 4H), 1.84 (m, 2H), 1.95 (m, 2H), 2.38 (s, 3H), 3.95 (m, 1H), 7.44 (d, 1H), 7.76 (dd, 1H), 7.96 (s, 1H), 8.05 (s, 1H), 8.18 (d, 1H), 8.42 (d, 1H), 8.77 (d, 1H), 11.23 (br, 1H), 11.36 (br, 1H).

Embodiment 316

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-the nicotinic acid methyl ester

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid methyl ester (100mg, 20%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (340mg 2mmol) prepares according to common processes Q with 6-sulfydryl-nicotinic acid methyl ester.

LC-MS(m/z)：497(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.64(m，4H)，1.85(m，4H)，2.33(s，3H)，3.79(m，1H)，3.99(s，3H)，7.10(dd，1H)，7.34(dd，1H)，7.71(s，1H)，7.79(s?1H)，8.22(dd，1H)，8.45(d，1H)，8.50(dd，1H)，8.79(s，1H)，11.50(br，1H)，11.75(br，1H).

Embodiment 317

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid (169mg, 70%) be from 6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(248mg 0.5mmol) prepares according to common processes J the nicotinic acid methyl ester.

LC-MS(m/z)：483(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.62(m，4H)，1.75(m，2H)，1.89(m，2H)，2.33(s，3H)，3.89(m，1H)，7.12(d，1H)，7.38(d，1H)，7.75(s，1H)，7.87(s，1H)，8.12(dd，2H)，8.24(dd，1H)，8.85(s，1H)，10.76(br，1H)，12.60(br，1H).

Embodiment 318

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-the nicotinic acid methyl ester

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-nicotinic acid methyl ester (172mg; 65%) be from 6-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(248mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for the nicotinic acid methyl ester.

LC-MS(m/z)：529(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.74(m，4H)，1.97(m，4H)，2.38(s，3H)，3.81(m，1H)，3.98(s，3H)，7.44(t，1H)，7.58(d，1H)，8.02(dd，1H)，8.11(s，1H)，8.23(d，1H)，8.52(dd，1H)，9.26(d，1H)，10.56(br，1H)，12.11(br，1H).

Embodiment 319

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-the pyridine-2-carboxylic acids methyl ester

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-pyridine-2-carboxylic acids methyl ester (149mg, 30%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (340mg 2mmol) prepares according to common processes Q with 3-sulfydryl-pyridine-2-carboxylic acids methyl ester.

LC-MS(m/z)：497(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.59(m，4H)，1.80(m，2H)，1.91(m，2H)，2.37(s，3H)，3.73(m，1H)，4.01(s，3H)，7.29(dd，1H)，7.36(d，1H)，7.52(dd，1H)，7.72(s，1H)，7.97(s，1H)，8.11(dd，1H)，8.46(m，1H)，11.83(br，1H).

Embodiment 320

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-pyridine-2-carboxylic acids

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-pyridine-2-carboxylic acids (181mg, 75%) be from 3-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(248mg 0.5mmol) prepares according to common processes J the pyridine-2-carboxylic acids methyl ester.

LC-MS(m/z)：483(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.62(m，4H)，1.75(m，2H)，1.91(m，2H)，2.32(s，3H)，3.88(m，1H)，7.38(d，2H)，7.51(dd，1H)，7.72(s，1H)，7.87(s，1H)，8.13(d，1H)，8.44(d，1H)，10.74(br，1H)，12.25(br，1H).

Embodiment 321

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-1H-imidazoles-4-carboxylic acid ethyl ester

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-1H-imidazoles-4-carboxylic acid ethyl ester (190mg, 38%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (340mg 2mmol) prepares according to common processes Q with 2-sulfydryl-1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS(m/z)：500(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.27(t，3H)，1.62(m，4H)，1.72(m，2H)，1.89(m，2H)，2.34(s，3H)，3.87(m，1H)，4.16(q，2H)，6.60(br，1H)，7.39(d，1H)，7.70(s，1H)，7.82(s，2H)，8.15(d，1H)，10.22(br，1H)，11.90(br，1H).

Embodiment 322

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-1H-imidazoles-4-carboxylic acid (167mg, 71%) be from 2-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-(250mg 0.5mmol) prepares according to common processes J 1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS(m/z)：472(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.61(m，4H)，1.73(m，2H)，1.89(m，2H)，2.33(s，3H)，3.87(m，1H)，6.53(br，1H)，7.37(d，1H)，7.64(s，1H)，7.83(s，2H)，8.14(d，1H)，10.70(br，1H)，12.20(br，1H).

Embodiment 323

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-1H-imidazoles-4-carboxylic acid ethyl ester

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-1H-imidazoles-4-carboxylic acid ethyl ester (181mg; 68%) be from 2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-(250mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for 1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS(m/z)：532(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.27(t，3H)，1.71(m，4H)，1.91(m，4H)，2.36(s，3H)，3.73(m，1H)，4.38(q，2H)，6.98(s，1H)，7.34(d，1H)，7.71(s，1H)，7.83(s，1H)，8.22(br，1H)，8.38(d，1H)，11.80(br，1H).

Embodiment 324

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-1H-imidazoles-4-carboxylic acid (171mg; 68%) be from 2-{2-[3-(2-pentamethylene-carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base alkylsulfonyl }-(266mg 0.5mmol) prepares according to common processes J 1H-imidazoles-4-carboxylic acid ethyl ester.

LC-MS(m/z)：504(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.61(m，4H)，1.75(m，2H)，1.89(m，2H)，2.33(s，3H)，3.88(m，1H)，7.41(d，1H)，7.53(dd，2H)，7.69(dd，1H)，7.88(m，1H)，8.01(br，1H)，8.14(d，1H)，10.86(br，1H).

Embodiment 325

(3-pentamethylene carbonyl-4-{3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl)-the acetic acid ethyl ester

(3-pentamethylene carbonyl-4-{3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl)-acetic acid ethyl ester (153mg, 30%) be from { 4-[3-(5-bromo-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid ethyl ester (480mg, 1mmol) (222mg 2mmol) prepares according to common processes Q with 2-sulfydryl-pyridine.

LC-MS(m/z)：511(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.26(t，3H)，1.61(m，4H)，1.85(m，4H)，3.62(s，2H)，3.76(m，1H)，4.16(q，2H)，7.01(dd，1H)，7.06(d，1H)，7.45(d，1H)，7.51(d，1H)，7.89(s，1H)，7.93(s，1H)，8.41(dd，1H)，8.55(d，1H)，11.70(br，1H)，11.89(br，1H).

Embodiment 326

(3-pentamethylene carbonyl-4-{3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl)-acetic acid

(3-pentamethylene carbonyl-4-{3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl)-acetic acid (173mg, 72%) be from (3-pentamethylene carbonyl-4-{3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea groups-phenyl)-(255mg is 0.5mmol) according to common processes J preparation for the acetic acid ethyl ester.

LC-MS (m/z): 483 (M+1) ^{+ 1}H NMR (400MHz, acetone d ₆): δ 1.64 (m, 4H), 1.86 (m, 2H), 1.98 (m, 4H), 3.71 (s, 2H), 3.94 (m, 1H), 7.08 (d, 1H), 7.15 (dd, 1H), 7.53 (d, 1H), 7.61 (s, 1H), 7.68 (m, 1H), 8.11 (s, 1H), 8.39 (m, 1H), 8.52 (d, 1H), 11.30 (br, 1H), 11.35 (br, 1H).

Embodiment 327

(3-pentamethylene carbonyl-4-{3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl) the acetic acid ethyl ester

(3-pentamethylene carbonyl-4-{3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl) acetic acid ethyl ester (120mg, 24%) be from { 4-[3-(5-bromo-thiazol-2-yl)-urea groups]-3-pentamethylene carbonyl-phenyl }-acetic acid ethyl ester (480mg, 1mmol) (200mg 2mmol) prepares according to common processes Q with 1H-imidazoles-2-mercaptan.

LC-MS(m/z)：500(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.21(t，3H)，1.58(m，4H)，1.83(m，4H)，3.61(m，3H)，4.17(q，1H)，6.73(s，1H)，7.04(m，2H)，7.38(d，1H)，7.61(br，1H)，7.81(s，1H)，8.41(d，1H)，11.23(br，1H)，11.49(br，1H).

Embodiment 328

(3-pentamethylene carbonyl-4-{3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl)-acetic acid

(3-pentamethylene carbonyl-4-{3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea groups }-phenyl)-acetic acid (177mg, 72%) be from (3-pentamethylene carbonyl-4-{3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea groups-phenyl)-(250mg is 0.5mmol) according to common processes J preparation for the acetic acid ethyl ester.

LC-MS (m/z): 472 (M+1) ^{+ 1}H NMR (400MHz, acetone d ₆): δ 1.61 (m, 4H), 1.91 (m, 4H), 3.58 (s, 2H), 3.72 (m, 1H), 6.77 (s, 1H), 7.04 (d, 1H), 7.33m, 2H), 7.64 (br, 1H), 7.80 (s, 1H), 8.43 (d, 1H), 11.44 (br, 1H), 11.59 (br, 1H).

Embodiment 329

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea (133mg, 30%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (202mg 2mmol) prepares according to common processes Y with 1-methyl isophthalic acid H-tetrazolium-5-mercaptan.

LC-MS(m/z)：444(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ1.70(m，4H)，1.91(m，4H)，2.37(s，3H)，3.78(m，1H)，4.06(s，3H)，7.37(d，1H)，7.73(s，1H)，7.93(s，1H)，8.41(d，1H)，9.30(br，1H)，11.74(br，1H).

Embodiment 330

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-tetrazolium-1-yl)-acetic acid

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-tetrazolium-1-yl)-acetic acid (136mg, 28%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (320mg 2mmol) prepares according to common processes Y with (5-sulfydryl-tetrazolium-1-yl)-acetic acid.

LC-MS(m/z)：488(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.70(m，4H)，1.91(m，4H)，2.34(s，3H)，3.89(m，1H)，5.48(s，2H)，7.42(d，1H)，7.81(s，1H)，7.88(s，1H)，8.17(d，1H)，10.76(br，1H)，12.25(br，2H).

Embodiment 331

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1 H-tetrazolium-5-base sulfenyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-base sulfenyl]-thiazol-2-yl }-urea (125mg, 25%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) and 1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-mercaptan (346mg is 2mmol) according to common processes Y preparation.

LC-MS(m/z)：501(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.70(m，4H)，1.91(m，4H)，2.28(s，6H)，2.34(s，3H)，2.76(t，2H)，3.74(m，1H)，4.42(t，2H)，7.32(d，1H)，7.68(s，1H)，7.83(s，1H)，8.36(d，1H)，11.25(br，1H)，11.40(br，1H).

Embodiment 332

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4] triazole-3-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4] triazole-3-base sulfenyl)-thiazol-2-yl]-urea (129mg, 30%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) and 2H-[1,2,4] (202mg 2mmol) prepares according to common processes Y triazole-3-mercaptan.

LC-MS(m/z)：429(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.63(m，4H)，1.70(m，2H)，1.91(m，2H)，2.34(s，3H)，3.89(m，1H)，7.41(d，1H)，7.63(s，1H)，7.87(s，1H)，8.17(d，1H)，10.72(br，1H)，12.18(br，1H).

Embodiment 333

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-base sulfenyl)-thiazol-2-yl]-urea (125mg, 25%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) with 4-methyl-4 H-[1,2,4] (230mg 2mmol) prepares according to common processes Y triazole-3-mercaptan.

LC-MS(m/z)：443(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.63(m，4H)，1.75(m，2H)，1.91(m，1H)，2.34(s，3H)，3.70(s，3H)，3.89(m，1H)，7.41(d，1H)，7.73(s，1H)，7.87(s，1H)，8.16(d，1H)，8.62(s，1H)，10.72(br，1H)，12.15(br，1H).

Embodiment 334

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1; 2; 4] triazole-3-alkylsulfonyl)-thiazol-2-yl]-urea (171mg; 72%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1; 2; 4] triazole-3-sulfenyl)-thiazol-2-yl]-(221mg, 0.5mmol) oxygenizement by m-cpba is according to common processes R preparation for urea.

LC-MS(m/z)：475(M+1)+，1H?NMR(400MHz，DMSO-d6)：δ1.73(m，4H)，1.85(m，2H)，1.91(m，2H)，2.34(s，3H)，3.70(s，3H)，3.89(m，1H)，7.51(d，1H)，7.73(s，1H)，7.87(s，1H)，8.16(d，1H)，8.62(s，1H)，10.72(br，1H)，12.15(br，1H).

Embodiment 335

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-phenyl)-acetic acid

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-phenyl)-acetic acid (140mg, 30%) be from 1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (408mg, 1mmol) (336mg 2mmol) prepares according to common processes Y with (4-sulfydryl-phenyl)-acetic acid.

(LC-MS(m/z)：496(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.63(m，4H)，1.75(m，2H)，1.91(m，2H)，2.33(s，3H)，3.59(s，2H)，3.89(m，1H)，7.20(m，3H)，7.40(d，2H)，7.68(s，1H)，7.87(s，1H)，8.16(d，1H)，12.36(br，3H).

Embodiment 336

1-(5-ethanoyl-4-methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-ethanoyl-4-methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (116mg; 60%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg; 0.5mmol) and 1-(2-amino-4-methyl-thiazole-5-yl)-(94mg 0.6mmol) prepares according to common processes D ethyl ketone.

LC-MS(m/z)：386(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.63(m，4H)，1.76(m，2H)，1.91(m，2H)，2.35(s，3H)，2.45(s，3H)，2.55(s，3H)，3.89(m，1H)，7.42(d，1H)，7.88(s，1H)，8.20(s，1H)，10.80(br，1H)，12.25(br，1H).

Embodiment 337

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-nitro-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-nitro-thiazol-2-yl)-urea (103mg, 55%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg, 0.5mmol) and 5-nitro-thiazol-2-yl amine (87mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：375(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.64(m，4H)，1.76(m，2H)，1.91(m，2H)，2.36(s，3H)，3.91(m，1H)，7.44(d，1H)，7.91(d，1H)，8.21(d，1H)，8.58(s，1H)，10.97(br，1H)，12.25(br，1H).

Embodiment 338

1-(the 4-tertiary butyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(the 4-tertiary butyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea (127mg, 66%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg, 0.5mmol) and the 4-tertiary butyl-thiazol-2-yl amine (94mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：386(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.24(s，9H)，1.62(m，4H)，1.76(m，2H)，1.91(m，2H)，2.32(s，3H)，3.87(m，1H)，6.63(s，1H)，7.37(d，1H)，7.83(d，1H)，8.13(d，1H)，10.53(br，1H)，11.82(br，1H).

Embodiment 339

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-pyridine-2-base-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-pyridine-2-base-urea (94mg, 58%) is that (102mg, 0.5mmol) (57mg 0.6mmol) prepares according to common processes D with the 2-aminopyridine from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone.

LC-MS(m/z)：324(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.63(m，4H)，1.76(m，2H)，1.91(m，2H)，2.35(s，3H)，3.90(m，1H)，6.03(d，1H)，7.42(d，1H)，7.80(m，4H)，8.21(s，1H)，10.77(br，1H)，12.24(br，1H).

Embodiment 340

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-formyl radical-thiazol-2-yl)-gland

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-formyl radical-thiazol-2-yl)-urea (116mg; 65%) be from (2-amino-5-methyl-phenyl)-cyclopentyl-ketone (102mg; 0.5mmol) and 2-amino-thiazolyl--5-formaldehyde (77mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：358(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.65(m，4H)，1.76(m，2H)，1.90(m，2H)，2.35(s，3H)，3.89(m?1H)，7.43(d，1H)，7.89(d，1H)，8.19(d，1H)，8.36(s，1H)，9.89(s，1H)，10.85(br，1H)，12.5(br，1H).

Embodiment 341

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(oximido-methyl)-thiazol-2-yl]-urea

At room temperature, to 2M NaHCO ₃(72mg, 0.2mmol) mixture in THF (5mL) adds oxammonium hydrochloride (200mg) to the aqueous solution (5mL), stirs simultaneously with 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-formyl radical-thiazol-2-yl)-urea.The gained mixture is heated 12h down at 60 ℃.With the reaction mixture cooling, use ethyl acetate extraction.With organic phase washing (salt solution), dry (Na ₂SO ₄), concentrate, obtain 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(oximido-methyl)-thiazol-2-yl]-urea (56mg, 76%), for cis-with trans-mixture of isomers.

LC-MS(m/z)：373(M+1) ⁺.

Embodiment 342

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylene amino oxygen base }-acetic acid

At room temperature, to 2M NaHCO ₃(72mg, 0.2mmol) mixture in THF (5mL) adds oxammonium hydrochloride (200mg) to the aqueous solution (5mL), stirs simultaneously with 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-formyl radical-thiazol-2-yl)-urea.The gained mixture is heated 12h down at 60 ℃.With the reaction mixture cooling, be acidified to pH6.5 (citric acid), use ethyl acetate extraction.With organic layer washing (salt solution), dry (Na ₂SO ₄), concentrate, obtain { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylene amino oxygen base }-acetic acid (56mg, 76%), for cis-with trans-mixture of isomers.

LC-MS(m/z)：431(M+1) ⁺.

Embodiment 343

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-the acetic acid methyl ester

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-acetic acid methyl ester (38mg; 45%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-formyl radical-thiazol-2-yl)-urea (0.072g, 0.2mmol) and glycine methyl ester hydrochloride according to common processes O preparation.

LC-MS(m/z)：431(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.64(m，4H)，1.76(m，2H)，1.91(m，2H)，2.33(s，3H)，3.33(s，2H)，3.35(br，1H)，3.63(s，3H)，3.83(s，2H)，3.91(m，1H)，7.14(s，1H)，7.38(d，1H)，7.83(s，1H)，8.17(s，1H)，10.63(br，1H)，11.56(br，1H).

Embodiment 344

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-the vinylformic acid ethyl ester

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-vinylformic acid ethyl ester (96mg; 80%) be from 1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-formyl radical-thiazol-2-yl)-urea (100mg; 0.28mmol) and (ethoxycarbonyl methylene radical)-triphenyl phosphine (0.12g is 0.34mmol) according to common processes X preparation.

LC-MS(m/z)：428(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ1.33(t，3H)，1.69(m，4H)，1.92(m，4H)，2.38(s，3H)，3.78(m，1H)，4.24(q，2H)，6.10(d，1H)，7.25(d，1H)，7.38(d，1H)，7.46(m，2H)，7.99(s，1H)，8.46(d，1H)，10.40(br，1H)，11.72(br，1H).

Embodiment 345

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-the propionic acid ethyl ester

3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-the propionic acid ethyl ester is from 3-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-the vinylformic acid ethyl ester prepares via hydrogenization under the described condition of common processes C.

LC-MS(m/z)：430(M+1) ⁺.

Embodiment 346

1-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-3-thiazol-2-yl-urea

(2-amino-4-methyl-phenyl)-(2-methoxyl group-phenyl)-ketone (723g, 30%) is that (1.51g 10mmol) prepares according to common processes S from 2-amino-4-methyl-phenylformic acid.1-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-3-thiazol-2-yl-urea (129mg; 70%) be from (2-amino-4-methyl-phenyl)-(2-methoxyl group-phenyl)-ketone (121mg; 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：368(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.42(s，3H)，3.75(s，3H)，6.78(d，1H)，6.91(d，1H)，6.98(d，1H)，7.04(t，1H)，7.26(t，1H)，7.33(d，1H)，7.46(m，1H)，7.64(d，1H)，8.46(s，1H)，11.02(br，1H)，11.67(br，1H).

Embodiment 347

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-thiazol-2-yl-urea

(2-amino-5-methyl-phenyl)-(2-methoxyl group-phenyl)-ketone (843g, 35%) is that (1.51g 0.1mol) prepares according to common processes S from 2-amino-5-methyl-phenylformic acid.1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-thiazol-2-yl-urea (132mg; 72%) be from (2-amino-5-methyl-phenyl)-(2-methoxyl group-phenyl)-ketone (121mg; 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：368(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.23(s，3H)，3.76(s，3H)，6.91(d，1H)，7.01(d，1H)，7.05(t，1H)，7.23(bs，1H)，7.29(d，1H)，7.36(d，1H)，7.48(t，1H)，7.59(d，1H)，8.48(s，1H)，10.56(br，1H)，11.45(br，1H).

Embodiment 348

1-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-thiazol-2-yl-urea

(2-amino-4-fluoro-phenyl)-(2-methoxyl group-phenyl)-ketone (784mg, 32%) is that (1.55g 0.1mol) prepares according to common processes S from 2-amino-4-fluoro-phenylformic acid.1-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-thiazol-2-yl-urea (127mg; 68%) be from (2-amino-4-fluoro-phenyl)-(2-methoxyl group-phenyl)-ketone (123mg; 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：372(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.75(s，3H)，6.66(m，1H)，6.93(d，1H)，6.98(t，1H)，7.05(t，1H)，7.29(d，1H)，7.48(m，2H)，7.63(d，1H)，8.45(dd，1H)，11.18(br，1H)，11.84(br，1H).

Embodiment 349

1-[5-fluoro-2-(thiophene-2-carbonyl)-phenyl]-3-thiazol-2-yl-urea

(2-amino-4-fluoro-phenyl)-thiophene-2-base-ketone (618g, 28%) is that (1.55g 10mmol) prepares according to common processes S from 2-amino-4-fluoro-phenylformic acid.N-[5-fluoro-2-(thiophene-2-carbonyl)-phenyl]-N '-(thiazol-2-yl) urea (113mg, 65%) be from (2-amino-4-fluoro-phenyl)-thiophene-2-base-ketone (110mg, 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：348(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ7.03(m，1H)，7.12(d，1H)，7.27(t，1H)，7.35(d，1H)，7.64(d，1H)，7.80(dd，1H)，8.07(d，1H)，8.14(d，1H)，9.63(br，1H)，11.60(br，1H).

Embodiment 350

N-[2-(2-methoxyl group-benzoyl)-5-methoxyl group-phenyl]-N '-(thiazol-2-yl) urea

(2-amino-4-methoxyl group-phenyl)-(2-methoxyl group-phenyl)-ketone (720mg, 28%) is that (1.67g 0.1mol) prepares according to common processes S from 2-amino-4-methoxyl group-phenylformic acid.N-[2-(2-methoxyl group-benzoyl)-5-methoxyl group-phenyl]-N '-(thiazol-2-yl) urea (131mg; 68%) be from (2-amino-4-methoxyl group-phenyl)-(2-methoxyl group-phenyl)-ketone (129mg; 0.5mmol) and thiazolamine (0.060g is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：384(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.77(s，3H)，3.93(s，3H)，6.91(d，1H)，6.98(d，1H)，7.04(t，1H)，7.23(d，1H)，7.25(d，1H)，7.36(d，1H)，7.45(m，1H)，7.54(br，1H)，8.27(d，1H)，10.20(br，1H)，12.10(br，1H).

Embodiment 351

(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl--phenyl]-urea groups }-thiazole-4-yl)-the acetic acid ethyl ester

(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid ethyl ester (163mg; 72%) be from (2-amino-4-methyl-phenyl)-(2-methoxyl group-phenyl)-ketone (121mg; 0.5mmol) and (2-amino-thiazolyl--4-yl)-acetic acid ethyl ester (111mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：454(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.25(t，3H)，2.40(s，3H)，3.69(s，2H)，3.72(s，3H)，4.20(q，2H)，6.71(s，1H)，6.76(d，1H)，6.96(d，1H)，7.02(t，1H)，7.23(d，1H)，7.30(d，1H)，7.44(t，1H)，8.47(s，1H)，9.47(br，1H)，11.57(br，1H).

Embodiment 352

(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid

(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid (181mg; 85%) be from (2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups-thiazole-4-yl)-(227mg is 0.5mmol) according to common processes J preparation for the acetic acid ethyl ester.

LC-MS(m/z)：426(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ2.36(s，3H)，3.57(s，2H)，3.68(s，3H)，6.86(s，1H)，7.07(t，1H)，7.22(m，2H)，7.31(d，1H)，7.50(t，2H)，8.26(s，1H)，10.92(br，1H)，12.20(br，1H).

Embodiment 353

2-(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide

2-(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide (164mg; 75%) be from (2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups-thiazole-4-yl)-acetic acid (213mg; 0.5mmol) and the THF solution of 1N methylamine (0.5mL is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：439(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.41(s，3H)，2.74(d，3H)，3.62(s，2H)，3.73(s，3H)，6.66(s，1H)，6.79(d，1H)，6.97(d，1H)，7.03(t，1H)，7.24(d，1H)，7.32(d，1H)，7.46(m，1H)，8.45(s，1H)，11.60(br，1H)，11.82(br，1H).

Embodiment 354

2-(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-(methoxyl group-ethyl)-ethanamide

2-(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-(methoxyl group-ethyl)-ethanamide (169mg; 70%) be from (2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups-thiazole-4-yl)-acetic acid (213mg; 0.5mmol) and 2-methoxy ethyl amine (38mg is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：483(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.41(s，3H)，3.33(s，3H)，3.48(m，4H)，3.61(s，2H)，3.73(s，3H)，6.65(s，1H)，6.76(d，1H)，6.97(d，1H)，7.03(t，1H)，7.25(d，1H)，7.31(d，1H)，7.42(bs，1H)，7.46(m，1H)，8.48(s，1H)，10.02(br，1H)，11.62(br，1H).

Embodiment 355

N-(2-methylsulfonyl-ethyl)-2-(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-ethanamide

N-(2-methylsulfonyl-ethyl)-2-(2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups }-thiazole-4-yl)-ethanamide (181mg; 68%) be from (2-{3-[2-(2-methoxyl group-benzoyl)-5-methyl-phenyl]-urea groups-thiazole-4-yl)-acetic acid (213mg; 0.5mmol) and 2-methylsulfonyl-ethylamine (61mg is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：531(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.41(s，3H)，2.93(s，3H)，3.33(t，3H)，3.63(s，2H)，3.74(s，3H)，3.78(m，2H)，6.61(s，1H)，6.76(d，1H)，6.98(d，1H)，7.04(t，1H)，7.25(d，1H)，7.31(d，1H)，7.46(m，1H)，7.97(t，1H)，8.48(s，1H)，11.40(br，1H)，11.51(br，1H).

Embodiment 356

(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-the acetic acid ethyl ester

(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-acetic acid ethyl ester (164mg; 72%) be from (2-amino-4-fluoro-phenyl)-(2-methoxyl group-phenyl)-ketone (123mg; 0.5mmol) and (2-amino-thiazolyl--4-yl)-acetic acid ethyl ester (111mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：458(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ1.24(t，3H)，3.68(s，2H)，3.78(s，3H)，6.68(s，1H)，6.74(d，1H)，6.93(d，1H)，7.06(t，1H)，7.24(m，1H)，7.30(d，1H)，7.44(t，1H)，8.47(s，1H)，9.47(br，1H)，11.57(br，1H).

Embodiment 357

(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-acetic acid

(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-acetic acid (161mg; 75%) be from (2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups-thiazole-4-yl)-the acetic acid ethyl ester (229,0.5mmol) according to common processes J preparation.

LC-MS(m/z)：430(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ3.57(s，2H)，3.69(s，3H)，6.89(m，2H)，7.08(t，1H)，7.18(d，1H)，7.33(d，1H)，7.40(m，1H)，7.54(m，1H)，8.28(d，1H)，11.12(br，1H)，12.32(br，1H).

Embodiment 358

2-(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide

2-(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide (144mg; 65%) be from (2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups-thiazole-4-yl)-acetic acid (215mg; 0.5mmol) and the THF solution of 1N methylamine (0.5mL is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：443(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.71(d，3H)，3.66(s，2H)，3.70(s，s，3H)，6.64m，2H)，6.85(br，1H)，7.36(m，2H)，6.95(d，1H)，7.02(t，1H)，7.24(dd，1H)，7.44(m，2H)，8.43(dd，1H)，10.72(br，1H)，11.84(br，1H).

Embodiment 359

2-(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-N-(2-methoxyl group-ethyl)-ethanamide

2-(2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-thiazole-4-yl)-N-(2-methoxyl group-ethyl)-ethanamide (158mg; 65%) be from (2-{3-[5-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups-thiazole-4-yl)-acetic acid (215mg; 0.5mmol) and the 2-methoxyethyl amine (38mg is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：487(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.21(s，3H)，3.48(m，4H)，3.62(s，2H)，3.73(s，3H)，6.62-6.66(m，2H)，6.97(d，1H)，7.04(t，1H)，7.28(d，1H)，7.42(br，1H)，7.42-7.50(m，2H)，8.46(dd，1H)，10.20(br，1H)，11.28(br，1H)，

Embodiment 360

1-[2-(oximido-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea

1-[2-(oximido-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea (101mg, 60%) be from (2-amino-phenyl)-phenyl-ketoxime (106mg, 0.5mmol) and thiazolamine (0.06mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：339(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ7.2(dd，1H)，7.06(d，1H)，7.15(m，1H)，7.30(d，1H)，7.34-7.43(m，6H)，8.03(d，1H)，8.05(br，1H)，11.07(br，1H)，11.63(br，1H)，

Embodiment 361

1-[5-chloro-2-(oximido-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea

1-[5-chloro-2-(oximido-phenyl-methyl)-phenyl]-3-thiazol-2-yl-urea (93mg, 50%) be from (2-amino-4-chloro-phenyl)-phenyl-ketoxime (123mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：373(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ7.04(dd，1H)，7.12(d，1H)，7.16(m，1H)，7.36(d，1H)，7.36-7.48(m，5H)，8.03(d，1H)，8.12(br，1H)，11.23(br，1H)，11.72(br，1H)，

Embodiment 362

1-(2-benzoyl-5-methyl-phenyl)-3-thiazol-2-yl-urea

1-(2-benzoyl-5-methyl-phenyl)-3-thiazol-2-yl-urea (60mg, 65%) is from ((55mg 0.25mmol) prepares according to common processes D 2-(2-amino-4-methyl-phenyl)-phenyl-ketone.

LC-MS(m/z)：338(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.40(s，3H)，6.93(s，1H)，7.19(t，1H)，7.28(s，1H)，7.48(t，1H)，7.54-7.61(m，4H)，7.68(dd，1H)，8.54(d，1H)，10.64(br，1H)，11.22(br，1H).

Embodiment 363

1-[4-bromo-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea

1-[4-bromo-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea (73mg, 69%) is that (73mg 0.25mmol) prepares according to common processes D from (2-amino-5-bromo-phenyl)-(2-fluoro-phenyl)-ketone.

LC-MS(m/z)：420(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ6.93(s，1H)，7.19(t，1H)，7.28(s，1H)，7.48(t，1H)，7.54-7.61(m，3H)，7.68(dd，1H)，8.54(d，1H)，10.64(br，1H)，11.22(br，1H).

Embodiment 364

1-[5-chloro-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea

1-[5-chloro-2-(2-fluoro-benzoyl)-phenyl]-3-thiazol-2-yl-urea (132mg; 70%) be from (2-amino-4-chloro-phenyl)-(2-fluoro-phenyl)-ketone (125mg; 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：376(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ6.76(s，1H)，6.89(s，1H)，7.16(m，1H)，7.25(d，1H)，7.48(m，4H)，8.58(br，1H)，10.88(br，1H).

Embodiment 365

1-[4-fluoro-2-(2-methylthio group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea

4-fluoro-2-(2-methylthio group phenoxy group)-1-oil of mirbane (1.06g, 68%) is that (0.77g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A 5-two fluoro-1-nitro-benzene from 2-hydroxyl thioanisole.According to common processes C, it is reduced to 4-fluoro-2-(2-methylthio group-phenoxy group)-phenyl amine (0.52g, 62%).1-[4-fluoro-2-(2-methylthio group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea (117mg, 60%) be from 4-fluoro-2-(2-methylthio group phenoxy group) aniline (125mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：376(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.41(s，3H)，6.41(dd，1H)，6.56(br，1H)，6.76(d，1H)，6.94(d，1H)，7.15-7.34(m，4H)，8.26(dd，1H)，9.88(br，1H)，11.12(br，1H)，

Embodiment 366

2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-6-methoxyl group-benzoic acid methyl ester

2-(4-fluoro-2-nitro-phenoxy group)-6-methoxyl group-benzoic acid methyl ester (0.94g, 58%) be from 2-hydroxyl-6-methoxyl group-benzoic acid methyl ester (1.01g, 5.5mmol) and 2,5-, two fluoro-1-nitro-benzene (0.80g is 5.0mmol) according to common processes A preparation.According to common processes C, it is reduced to 2-(2-amino-4-fluoro-phenoxy group)-6-methoxyl group-benzoic acid methyl ester (0.51g, 60%).2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-6-methoxyl group-benzoic acid methyl ester (129mg, 62%) be from 2-(2-amino-4-fluoro-phenoxy group)-6-methoxyl group-benzoic acid methyl ester (145mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：418(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.62(s，3H)，3.64(s，3H)，6.31(s，1H)，6.45(dd，1H)，6.55(s，1H)，7.05(d，1H)，7.22(t，1H)，7.33(br，1H)，7.45(d，1H)，78.02(d，1H)，8.63(br，1H)，11.74(br，1H).

Embodiment 367

2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-6-methoxyl group-N-methyl-benzamide

2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-6-methoxyl group-N-methyl-benzamide (150mg, 72%) be from 2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-6-methoxyl group-phenylformic acid (201mg, 0.5mmol) and the THF solution of 1N methylamine (0.5mL is 0.5mmol) according to common processes K preparation.

LC-MS(m/z)：417(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ3.42(d，3H)，3.67(s，3H)，6.51(dd，1H)，6.67(m，1H)，7.14(m，2H)，7.29(m，2H)，7.37(d，1H)，7.98(dd，1H)，8.11(d，1H)，9.13(dd，1H)，11.20(br，1H).

Embodiment 368

1-[5-fluoro-2-(2-methylsulfonyl-phenoxy group)-phenyl]-3-thiazol-2-yl-urea

1-[5-fluoro-2-(2-methylsulfonyl-phenoxy group)-phenyl]-3-thiazol-2-yl-urea (153mg, 75%) is from 1-[5-fluoro-2-(2-methylthio group-phenoxy group)-phenyl]-(187mg 0.5mmol) prepares according to common processes R 3-thiazol-2-yl-urea.

LC-MS(m/z)：408(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.44(s，3H)，6.80(m，1H)，6.84(d，1H)，7.03(d，1H)，7.27(m，2H)，7.33(d，1H)，7.56(m，1H)，8.05(dd，1H)，8.27(dd，1H)，9.13(br，1H)，11.12(br，1H).

Embodiment 369

1-[2-(4,5-dimethoxy-2-methyl-phenoxy group)-phenyl]-3-thiazol-2-yl-urea

1-[2-(4,5-dimethoxy-2-methyl-phenoxy group)-phenyl]-3-thiazol-2-yl-urea (131mg, 68%) is from 2-(4,5-dimethoxy-2-methyl-phenoxy group)-phenyl amine (130mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：386(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ2.29(s，3H)，3.80(s，3H)，3.94(s，3H)，6.76(s，1H)，6.92(d，1H)，7.02(t，1H)，7.44(d，1H)，7.55(t，2H)，7.76(d，1H)，8.54(d，1H)，11.34(br，1H).

Embodiment 370

3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-benzoic acid methyl ester

3-(4-fluoro-2-nitro-phenoxy group)-benzoic acid methyl ester (0.73g, 50%) is that (0.84g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A 5-two fluoro-1-nitro-benzene from 3-hydroxy-benzoic acid methyl ester.According to common processes C, it is reduced to 2-(2-amino-4-fluoro-phenoxy group)-benzoic acid methyl ester (0.37g, 58%).3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-benzoic acid methyl ester (145mg, 75%) be from 3-(2-amino-4-fluoro-phenoxy group)-benzoic acid methyl ester (130mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：388(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.87(s，3H)，6.78(m，1H)，6.89(d，1H)，7.12(m，1H)，7.18(br，1H)，7.34(m，1H)，7.41(m，1H)，7.60(m，1H)，7.72(d，1H)，8.22(dd，1H)，10.50(br，1H).

Embodiment 371

3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-phenylformic acid

3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-phenylformic acid (150mg, 80%) is from 3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-(194mg 0.5mmol) prepares according to common processes J benzoic acid methyl ester.

LC-MS(m/z)：374(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ6.85(m，1H)，7.01(dd，1H)，7.13(d，1H)，7.26(dd，1H)，7.34(d，1H)，7.42(m，1H)，7.52(t，1H)，8.14(dd，1H)，9.47(br，1H)，11.28，br，1H).

Embodiment 372

2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-benzoic acid methyl ester

2-(4-fluoro-2-nitro-phenoxy group)-benzoic acid methyl ester (0.81g, 55%) is that (0.84g, 5.5mmol) with 2, (0.80g 5.0mmol) prepares according to common processes A 5-two fluoro-1-nitro-benzene from 2-hydroxy-benzoic acid methyl ester.According to common processes C, it is reduced to 2-(2-amino-4-fluoro-phenoxy group)-benzoic acid methyl ester (0.43g, 60%).2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-benzoic acid methyl ester (125mg, 65%) be from 2-(2-amino-4-fluoro-phenoxy group)-benzoic acid methyl ester (130mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：388(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.84(s，3H)，6.73(m，1H)，6.85(d，1H)，7.14(m，1H)，7.13(br，1H)，7.31(m，1H)，7.41(m，1H)，7.54(m，1H)，7.71(d，1H)，8.22(dd，1H)，10.54(br，1H).

Embodiment 373

2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-N-methyl-benzamide

2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-N-methyl-benzamide is from 2-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-(0.5mL is 0.5mmol) according to common processes K preparation for the THF solution of phenylformic acid and 1N methylamine.

LC-MS(m/z)：387(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.53(d，3H)，6.73(m，1H)，5.86(br，1H)，6.88(d，1H)，7.16(m，1H)，7.18(br，1H)，7.35(m，1H)，7.41(m，1H)，7.60(m，1H)，7.76(d，1H)，8.23(dd，1H)，10.22(br，1H).

Embodiment 374

N-{3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-2-methoxyl group-phenyl }-Toluidrin

N-[3-(4-fluoro-2-nitro-phenoxy group)-2-methoxyl group-phenyl]-Toluidrin (0.86g, 48%) be from N-(3-hydroxyl-2-methoxyl group-phenyl)-Toluidrin (1.2g, 5.5mmol) and 2,5-, two fluoro-1-nitro-benzene (0.80g is 5.0mmol) according to common processes A preparation.According to common processes C, it is reduced to N-[3-(2-amino-4-fluoro-phenoxy group)-2-methoxyl group-phenyl]-Toluidrin (0.51g, 70%).N-{3-[4-fluoro-2-(3-thiazol-2-yl-urea groups)-phenoxy group]-2-methoxyl group-phenyl }-Toluidrin (144mg, 64%) be from N-[3-(2-amino-4-fluoro-phenoxy group)-2-methoxyl group-phenyl]-Toluidrin (123mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LC-MS(m/z)：453(M+1) ⁺； ¹H?NMR(400MHz，CDCl ₃)：δ3.27(s，3H)，3.89(s，3H)，6.52(d，1H)，6.72(m，1H)，6.95(d，1H)，7.04(m，1H)，7.16(m，1H)，7.34(d，1H)，7.45(dd，1H)，7.63(d，1H)，8.21(dd，1H)，8.44(br，1H)，8.85(br，1H).

Embodiment 375

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-ethanamide

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-ethanamide (81mg, 78%) be from N-[3-amino-4-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(72mg 0.25mmol) prepares according to common processes D ethanamide.

LC-MS (m/z): 417 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.78 (s, 3H), 3.43 (s, 3H), 6.32 (m, 1H), 6.44 (dd, 1H), 6.48 (d, 1H), 6.63 (t, 1H), 6.86 (dd, 1H), 6.97 (d, 1H), 7.13 (d, 1H), 7.88 (d, 1H), 8.90 (br, 1H), 9.32 (br, 1H) and 10.46 (br, 1H).

Embodiment 376

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-Toluidrin

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl] Toluidrin (101mg, 89%) be from N-[3-amino-4-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(81mg 0.25mmol) prepares according to common processes L Toluidrin.

LC-MS (m/z): 453 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 3.13 (s, 3H), 4.00 (s, 3H), 6.70 (d, 1H), 6.98 (dd, 1H), 7.14 (t, 1H), 7.21 (d, 1H), 7.38 (t, 1H), 7.46 (q, 1H), 7.55 (t, 1H), 8.14 (br, 1H), 8.38 (dd, 1H), 8.46 (d, 1H) and 10.86 (br, 1H).

Embodiment 377

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups }-thiazole-4-yl)-the acetic acid ethyl ester

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups }-thiazole-4-yl)-acetic acid ethyl ester (118mg, 87%) be from N-[3-amino-4-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(81mg 0.25mmol) prepares according to common processes D Toluidrin.

LC-MS (m/z): 539 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 1.24 (t, 2H), 3.03 (s, 3H), 3.74 (s, 2H), 3.80 (s, 3H), 4.21 (q, 3H), 6.59 (d, 1H), 6.68 (s, 1H), 6.78 (s, 1H), 6.83 (dd, 1H), 7.12-7.19 (m, 2H), 8.12 (d, 1H), 8.42 (s, 1H), 9.60 (br, 1H) and 11.84 (br, 1H).

Embodiment 378

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups }-thiazole-4-yl)-acetic acid

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups }-thiazole-4-yl)-acetic acid (85mg, 83%) be from (2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups-thiazole-4-yl)-(108mg is 0.20mmol) according to common processes J preparation for the acetic acid ethyl ester.

LC-MS (m/z): 511 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.12 (s, 3H), 3.54 (s, 2H), 3.81 (s, 3H), 6.54 (d, 1H), 6.64 (s, 1H), 6.84 (s, 1H), 6.92 (d, 1H), 7.11 (m, 1H), 7.16 (s, 1H), 7.44 (m, 1H), 8.46 (s, 1H), 9.40 (br, 1H), 10.83 (br, 1H) and 11.84 (br, 1H).

Embodiment 379

N, N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl] two Toluidrins

N, N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl] two Toluidrin (115mg, 87%) being from N-[3-amino-4-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl] (101mg 0.25mmol) prepares according to common processes D-two Toluidrins.

LC-MS (m/z): 531 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 3.22 (s, 3H), 3.24 (s, 3H), 4.11 (s, 3H), 6.78 (d, 1H), 6.89 (d, 1H), 7.11 (dd, 1H), 7.24 (d, 1H), 7.29 (m, 1H), 7.42 (t, 1H), 7.63 (m, 1H), 8.54 (d, 1H), 8.65 (dd, 1H) and 11.38 (br, 1H).

Embodiment 380

N-[4-isobutoxy-3-(3-thiazol-2-yl-urea groups)-phenyl]-Toluidrin

N-[4-isobutoxy-3-(3-thiazol-2-yl-urea groups)-phenyl]-Toluidrin (77mg, 80%) is that (64mg 0.25mmol) prepares according to common processes D from N-(3-amino-4-isobutoxy-phenyl)-Toluidrin.

LC-MS (m/z): 385 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.20 (d, 6H), 1.70 (m, 1H), 3.05 (d, 2H), 3.82 (s, 3H), 6.76 (dd, 1H), 6.86 (d, 1H), 6.94 (m, 1H), 7.36 (d, 1H), 7.42 (d, 1H), 8.42 (d, 1H), 9.56 (br, 1H) and 11.63 (br, 1H).

Embodiment 381

1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea

1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea (3.52g; 94%) be from 3-amino-4-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-carboxylamine tertiary butyl ester (3.48g; 10.0mmol) prepare according to common processes D; again product [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-carboxylamine tertiary butyl ester of corresponding t-BOC protection is gone protection with hydrochloric acid (40mL, the 4.0M solution in two _ alkane).

LC-MS (m/z): 375 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.76 (s, 3H), 5.24 (br, 2H), 6.68 (d, 1H), 6.88 (q, 1H), 6.98 (d, 1H), 7.16 (m, 1H), 7.38 (dd, 1H), 7.63 (dd, 1H), 8.34 (dd, 1H), 8.44 (d, 1H), 8.86 (br, 1H) and 11.27 (br, 1H).

Embodiment 382

Pyridine-2-carboxylic acids [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

Pyridine-2-carboxylic acids [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (98mg, 82%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes K 3-thiazol-2-yl-urea.

LC-MS (m/z): 480 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 3.74 (s, 3H), 6.64 (d, 1H), 6.74 (d, 1H), 6.78 (s, 1H), 6.82 (m, 1H), 7.16 (q, 1H), 7.46 (dd, 1H), 7.48 (d, 1H), 7.54 (t, 1H), 7.72 (br, 1H), 7.84 (dd, 1H), 7.88 (t, 1H), 8.24 (d, 1H), 8.38 (br, 1H), 8.62 (d, 1H) and 10.06 (br, 1H).

Embodiment 383

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-Isonicotinamide

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-Isonicotinamide (104mg, 86%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes K 3-thiazol-2-yl-urea.

LC-MS (m/z): 480 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.58 (s, 3H), 6.32 (d, 1H), 6.62 (dd, 1H), 6.64 (d, 1H), 6.66 (d, 1H), 6.96 (m, 2H), 7.06 (d, 1H), 7.18 (dd, 1H), 7.60 (d, 2H), 8.12 (d, 1H), 8.40 (br, 1H), 8.48 (d, 1H), 9.62 (d, 1H) and 11.34 (br, 1H).

Embodiment 384

5-methyl-pyrazine-2-carboxylic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

5-methyl-pyrazine-2-carboxylic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (103mg, 83%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes K 3-thiazol-2-yl-urea.

LC-MS (m/z): 495 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 2.68 (s, 3H), 3.63 (s, 3H), 6.52 (d, 1H), 6.61 (d, 1H), 6.66 (d, 2H), 7.06 (q, 1H), 7.36 (s, 1H), 7.78 (d, 1H), 8.20 (br, 1H), 8.43 (s, 1H), 8.76 (br, 1H), 9.32 (s, 1H), 9.62 (s, 1H) and 11.80 (br, 1H).

Embodiment 385

2,2,2-, three fluoro-ethyl sulfonic acids [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

2,2,2-three fluoro-ethyl sulfonic acids [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (105mg, 81%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 521 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.75 (s, 3H), 3.86 (q, 2H), 6.48 (d, 1H), 6.80 (m, 2H), 6.88 (d, 1H), 7.16 (q, 1H), 7.28 (d, 1H), 7.47 (s, 1H), 8.08 (d, 1H), 8.40 (br, 1H), 9.62 (d, 1H) and 11.34 (br, 1H).

Embodiment 386

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-C-methylsulfonyl-Toluidrin

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-C-methylsulfonyl-Toluidrin (102mg; 77%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 530 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.01 (s, 3H), 3.27 (s, 2H), 3.82 (s, 3H), 6.56 (d, 1H), 6.85 (t, 1H), 6.94 (d, 1H), 7.21 (q, 1H), 7.34 (d, 1H), 7.46 (m, 1H), 7.96 (s, 1H), 8.22 (d, 1H), 8.40 (br, 1H), 9.62 (br, 1H) and 10.94 (br, 1H).

Embodiment 387

1-methyl isophthalic acid H-imidazoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

1-methyl isophthalic acid H-imidazoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (108mg, 83%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 519 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.00 (s, 3H), 3.78 (s, 3H), 6.46 (d, 1H), 6.74 (dd, 1H), 6.83 (d, 2H), 6.91 (d, 1H), 7.16-7.22 (m, 1H), 7.31 (d, 1H), 7.48 (m, 1H), 7.66 (s, 1H), 7.99 (d, 1H), 8.18 (d, 1H), 9.88 (br, 1H) and 11.24 (br, 1H).

Embodiment 388

1,2-dimethyl-1H-imidazoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

1,2-dimethyl-1H-imidazoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (115mg, 86%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 533 (M+1) ^{+ 1}H NMR (400MHz, DMSO-d ₆): δ 2.74 (s, 3H), 3.20 (s, 3H), 3.99 (s, 3H), 6.79 (d, 1H), 7.09 (dd, 1H), 7.34 (t, 1H), 7.44 (d, 1H), 7.48 (d, 1H), 7.67 (q, 1H), 7.78 (d, 1H), 8.01 (s, 1H), 8.36 (s, 1H), 8.46 (d, 1H), 9.88 (br, 1H) and 11.24 (br, 1H).

Embodiment 389

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methylamino-phenyl]-3-thiazol-2-yl-urea

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methylamino-phenyl]-3-thiazol-2-yl-urea (85mg, 88%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes O 3-thiazol-2-yl-urea.

LC-MS (m/z): 389 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 3.66 (s, 3H), 4.09 (s, 3H), 5.62 (br, 1H), 6.82 (d, 1H), 6.99 (s, 1H), 7.16 (m, 1H), 7.40 (d, 1H), 7.45-7.53 (m, 1H), 7.58 (d, 1H), 7.64 (d, 1H), 8.76 (d, 1H), 9.38 (br, 1H) and 11.27 (br, 1H).

Embodiment 390

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-(1-methyl-3-thiazol-2-yl-urea groups)-phenyl]-3-thiazol-2-yl-urea

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-(1-methyl-3-thiazol-2-yl-urea groups)-phenyl]-3-thiazol-2-yl-urea (86mg, 67%) be from 4-(2-fluoro-6-methoxyl group-phenoxy group)-N ' 1 '-methyl-benzene-1, (64mg 0.25mmol) prepares according to common processes D the 3-diamines.

LC-MS (m/z): 515 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 3.32 (s, 3H), 3.73 (s, 3H), 5.40 (br, 1H), 6.46 (d, 2H), 6.54 (d, 1H), 6.74 (d, 1H), 6.80 (d, 1H), 7.08 (d, 2H), 7.22 (d, 1H), 7.33 (br, 1H), 8.38 (d, 1H), 9.03 (br, 1H) and 11.27 (br, 1H).

Embodiment 391

1-[5-dimethylamino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea

1-[5-dimethylamino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea (85mg, 85%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes O 3-thiazol-2-yl-urea.

LC-MS (m/z): 403 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 2.93 (s, 6H), 3.66 (s, 3H), 6.38 (d, 1H), 6.49 (t, 1H), 6.62-6.74 (m, 2H), 7.07 (t, 1H), 7.39 (d, 1H), 7.84 (s, 1H), 8.00 (br, 1H), 8.42 (br, 1H) and 11.52 (br, 1H).

Embodiment 392

1-{2-(2-fluoro-6-methoxyl group-phenoxy group)-5-[(pyridin-3-yl methyl)-amino]-phenyl }-3-thiazol-2-yl-urea

1-{2-(2-fluoro-6-methoxyl group-phenoxy group)-5-[(pyridin-3-yl methyl)-amino]-phenyl }-3-thiazol-2-yl-urea (98mg, 84%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes O 3-thiazol-2-yl-urea.

LC-MS (m/z): 466 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.16 (s, 2H), 3.62 (s, 3H), 6.42 (d, 1H), 6.68 (t, 1H), 6.78 (d, 1H), 6.88 (m, 1H), 7.05 (q, 1H), 7.21 (s, 1H), 7.41 (m, 1H), 7.52 (m, 1H), 7.81 (br, 1H), 8.00 (br, 1H), 8.16 (d, 1H), 8.42 (d, 1H), 8.56 (d, 1H), 8.70 (m, 1H) and 11.38 (br, 1H).

Embodiment 393

1-[5-(two-pyridine-2-base-amino)-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea

1-[5-(two-pyridine-2-base-amino)-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-3-thiazol-2-yl-urea (111mg, 84%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes O 3-thiazol-2-yl-urea.

LC-MS (m/z): 529 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.67 (s, 3H), 6.42 (d, 1H), 6.46 (d, 1H), 6.50 (d, 2H), 6.72 (q, 2H), 6.87 (m, 4H), 7.02-7.10 (m, 2H), 7.42 (m, 1H), 7.54 (m, 1H), 8.14 (d, 2H), 9.70 (br, 1H) and 11.58 (br, 1H).

Embodiment 394

Propane-1-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

Propane-1-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (100mg, 83%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 481 (M+1) ^{+ 1}H NMR (400MHz, acetone-d ₆): δ 1.02 (t, 3H), 1.84 (m, 2H), 3.08 (t, 2H), 3.82 (s, 3H), 6.56 (d, 1H), 6.88 (d, 1H), 6.96-7.00 (m, 1H), 7.24 (q, 1H), 7.34 (dd, 1H), 7.88 (s, 1H), 7.99 (br, 1H), 8.32 (d, 1H), 8.48 (d, 1H), 8.64 (br, 1H) and 11.12 (br, 1H).

Embodiment 395

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-C-phenyl methanesulfonamide acid amides

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-C-phenyl methanesulfonamide acid amides (104mg, 79%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 529 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.36 (s, 2H), 3.83 (s, 3H), 6.54 (d, 1H), 6.86 (m, 2H), 6.94 (m, 2H), 7.22 (q, 1H), 7.38 (m, 5H), 7.42 (d, 1H), 7.96 (br, 1H), 8.06 (d, 1H), 9.34 (br, 1H) and 11.24 (br, 1H).

Embodiment 396

N-{4-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl sulfamoyl base]-phenyl }-ethanamide

N-{4-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl sulfamoyl base]-phenyl }-ethanamide (113mg; 79%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 572 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.02 (s, 3H), 3.85 (s, 3H), 6.48 (d, 1H), 6.86 (m, 2H), 6.98 (br, 1H), 7.03 (m, 2H), 7.41 (m, 3H), 7.76 (m, 3H), 8.23 (d, 1H), 9.06 (br, 1H), 9.54 (br, 1H) and 11.24 (br, 1H).

Embodiment 397

1-{2-(2-fluoro-6-methoxyl group-phenoxy group)-5-[(5-methyl-3H-imidazol-4 yl methyl)-amino]-phenyl }-3-thiazol-2-yl-urea

1-{2-(2-fluoro-6-methoxyl group-phenoxy group)-5-[(5-methyl-3H-imidazol-4 yl methyl)-amino]-phenyl }-3-thiazol-2-yl-urea (98mg, 84%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes O 3-thiazol-2-yl-urea.

LC-MS (m/z): 469 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 2.29 (s, 3H), 2.55 (s, 2H), 3.68 (s, 3H), 6.46 (d, 1H), 6.86 (m, 2H), 6.96 (br, 1H), 7.08 (d, 1H), 7.41 (m, 1H), 7.49 (m, 2H), 7.54s, 1H), 7.64 (s, 1H), 7.72 (d, 1H), 9.46 (br, 1H) and 11.44 (br, 1H).

Embodiment 398

4-ethanoyl-N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-benzsulfamide

4-ethanoyl-N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-benzsulfamide (98mg; 84%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 557 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 2.61 (s, 3H), 3.78 (s, 3H), 6.48 (d, 1H), 6.88 (m, 2H), 7.06 (m, 2H), 7.08 (d, 1H), 7.22 (br, 1H), 7.36 (d, 1H), 7.82 (m, 1H), 7.92 (d, 2H), 7.98 (t, 1H), 8.12 (d, 1H), 8.24 (br, 1H) and 11.88 (br, 1H).

Embodiment 399

4-cyano group-N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl] benzsulfamide

4-cyano group-N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl] benzsulfamide (115mg, 85%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 540 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 3.76 (s, 3H), 6.52 (d, 1H), 6.80 (m, 1H), 6.88 (d, 1H), 7.08 (d, 2H), 7.12-7.18 (m, 1H), 7.30 (d, 1H), 7.38 (d, 1H), 7.54 (d, 1H), 7.71 (t, 1H), 7.91 (q, 1H), 8.01 (s, 1H), 8.08 (br, 1H), 8.22 (d, 1H) and 11.22 (br, 1H).

Embodiment 400

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-4-sec.-propyl-benzsulfamide

N-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-4-sec.-propyl-benzsulfamide (103mg, 74%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 557 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 1.22 (d, 6H), 1.56 (m, 1H), 3.74 (s, 3H), 6.54 (d, 1H), 6.78 (m, 2H), 6.84 (d, 1H), 6.98 (m, 1H), 7.06 (d, 1H), 7.12-7.18 (m, 2H), 7.22 (d, 1H), 7.34 (d, 1H), 7.72 (d, 1H), 8.00 (br, 1H), 8.22 (d, 1H), 8.58 (br, 1H) and 10.74 (br, 1H).

Embodiment 401

N-{5-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl sulfamoyl base]-4-methyl-thiazol-2-yl }-ethanamide

N-{5-[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl sulfamoyl base]-4-methyl-thiazol-2-yl }-ethanamide (121mg; 82%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 593 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 2.32 (s, 3H), 3.00 (s, 3H), 3.77 (s, 3H), 4.04 (br, 1H), 6.48 (d, 1H), 6.84 (d, 1H), 6.88 (dd, 1H), 6.96 (d, 1H), 7.16-7.22 (m, 1H), 7.32 (d, 1H), 7.36 (d, 1H), 7.92 (d, 1H), 7.98 (br, 1H), 8.84 (br, 1H) and 10.74 (br, 1H).

Embodiment 402

5-bromo-6-chloro-pyridine-3-sulphonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

5-bromo-6-chloro-pyridine-3-sulphonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (120mg, 76%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 629 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 3.78 (s, 3H), 6.56 (d, 1H), 6.88 (d, 1H), 6.78 (m, 1H), 6.88 (dd, 1H), 7.14 (d, 1H), 7.22 (d, 1H), 7.36 (d, 1H), 8.02 (d, 1H), 8.12 (br, 1H), 8.33 (d, 1H), 8.73 (d, 1H), 9.78 (br, 1H) and 10.74 (br, 1H).

Embodiment 403

3,5-dimethyl-different _ azoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

3,5-dimethyl-different _ azoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (98mg, 73%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 534 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 2.88 (s, 3H), 3.00 (s, 3H), 3.75 (s, 3H), 5.21 (br, 1H), 6.54 (d, 1H), 6.80-6.88 (m, 1H), 6.96 (m, 1H), 7.10-7.20 (m, 1H), 7.38 (d, 1H), 7.52 (d, 1H), 7.72 (br, 1H), 8.01 (d, 1H), 8.22 (d, 1H) and 10.74 (br, 1H).

Embodiment 404

5-chloro-1,3-dimethyl-1H-pyrazoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

5-chloro-1,3-dimethyl-1H-pyrazoles-4-sulfonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (111mg, 79%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 568 (M+1) ^{+ 1}H NMR (400MHz, CDCl ₃): δ 2.32 (s, 3H), 2.63 (s, 3H), 3.74 (s, 3H), 6.48 (d, 1H), 6.76-6.84 (m, 1H), 6.94 (d, 1H), 7.06-7.18 (m, 1H), 7.22 (d, 1H), 7.38 (d, 1H), 7.52 (d, 1H), 7.94 (d, 1H), 8.08 (d, 1H), 8.20 (br, 1H) and 11.16 (br, 1H).

Embodiment 405

6-morpholine-4-base-pyridine-3-sulphonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

6-morpholine-4-base-pyridine-3-sulphonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (115mg, 76%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 601 (M+1) ^{+ 1}H NMR (400MHz, CD ₃0D): δ 2.15 (m, 4H), 3.60 (t, 2H), 3.70 (t, 2H), 3.76 (s, 3H), 6.42 (d, 1H), 6.78 (d, 2H), 6.84 (d, 1H), 6.96 (d, 1H), 7.04 (m, 2H), 7.20 (m, 1H), 7.34 (d, 1H), 7.79 (d, 1H), 8.02 (d, 1H), 8.39 (d, 1H), 8.52 (br, 1H) and 11.28 (br, 1H).

Embodiment 406

6-_ azoles-5-base-pyridine-3-sulphonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides

6-_ azoles-5-base-pyridine-3-sulphonic acid [4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-acid amides (96mg, 66%) be from 1-[5-amino-2-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(94mg 0.25mmol) prepares according to common processes L 3-thiazol-2-yl-urea.

LC-MS (m/z): 583 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 3.77 (s, 3H), 6.46 (d, 1H), 6.78-6.86 (m, 2H), 6.94 (d, 1H), 6.92-6.99 (m, 2H), 7.20 (q, 1H), 7.33 (dd, 1H), 7.55 (d, 1H), 7.80 (d, 1H), 7.86-7.92 (m, 2H), 8.05 (d, 1H), 8.18 (d, 1H), 9.88 (br, 1H) and 11.16 (br, 1H).

Embodiment 407

2-(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide (47mg, 87.9%) be from (2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methanesulfonamido-phenyl]-urea groups-thiazole-4-yl)-(51mg is 0.10mmol) according to common processes K preparation for acetic acid.

LC-MS (m/z): 524 (M+1) ^{+ 1}H NMR (400MHz, CD ₃OD): δ 2.93 (s, 3H), 3.48 (d, 3H), 3.56 (s, 2H), 4.02 (s, 3H), 4.82 (br, 1H), 6.76 (d, 1H), 7.04 (s, 1H), 7.09 (dd, 1H), 7.16 (t, 1H), 7.22 (d, 1H), 7.52 (q, 1H), 8.12 (br, 1H), 8.44 (d, 1H), 9.88 (br, 1H) and 11.84 (br, 1H).

Embodiment 408

[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-carboxylamine tertiary butyl ester

[4-(2-fluoro-6-methoxyl group-phenoxy group)-3-(3-thiazol-2-yl-urea groups)-phenyl]-carboxylamine tertiary butyl ester (4.56g, 96.2%) be from 3-amino-4-(2-fluoro-6-methoxyl group-phenoxy group)-phenyl]-(3.48g 10.0mmol) prepares according to common processes D the carboxylamine tertiary butyl ester.

LC-MS(m/z)：475(M+1) ⁺； ¹H?NMR(400MHz，CD ₃OD)：δ1.74(s，9H)，3.74(s，3H)，6.64(d，1H)，6.92(dd，1H)，7.02(d，1H)，7.14(m，1H)，7.34(dd，1H)，7.68(dd，1H)，7.88(br，1H)，8.32(dd，1H)，8.46(d，1H)，9.26(br，1H)，11.62(br，1H).

Embodiment 409

1-(4-methyl-2-propoxy--phenyl)-3-thiazol-2-yl-urea

3-propoxy--4-nitrotoluene (0.79g, 80%) is that (0.77g is 5.0mmol) according to common processes G preparation from 1-propyl alcohol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 4-methyl-2-propoxy-aniline (0.54g, 82%).1-(4-methyl-2-propoxy--phenyl)-3-thiazol-2-yl-urea (220mg, 75%) be from 4-methyl-2-propoxy-aniline (165mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：292(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.03(t，3H)，1.80(m，2H)，2.25(s，3H)，3.98(t，2H)，6.70(dd，1H)，6.83(d，1H)，7.10(d，1H)，7.37(d，1H)，7.98(d，1H)，8.50(br，1H)，11.27(br，1H).

Embodiment 410

1-(2-butoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-(1-butoxy)-4-nitrotoluene (0.78g, 75%) is that (0.77g is 5.0mmol) according to common processes G preparation from 1-butanols and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 4-methyl-2-(1-butoxy) aniline (0.47g, 70%).1-(2-butoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (210mg, 70%) be from 4-methyl-2-(1-butoxy) aniline (179mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：306(M+1) ⁺； ¹H?NMR(400?MHz，DMSO-d ₆)：δ0.95(t，3H)，1.52(m，2H)，1.78(m，2H)，2.25(s，3H)，4.04(t，2H)，6.71(dd，1H)，6.86(d，1H)，7.11(d，1H)，7.36(d，1H)，7.96(d，1H)，8.50(br，1H)，11.26(br，1H).

Embodiment 411

1-[4-methyl-2-(3-methyl-butoxy)-phenyl]-3-thiazol-2-yl-urea

3-(3-methyl-butoxy)-4-nitrotoluene (0.89g, 80%) is that (0.77g is 5.0mmol) according to common processes G preparation from 3-methyl butanol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 4-methyl-2-(3-methyl butoxy) aniline (0.55g, 72%).1-[4-methyl-2-(3-methyl-butoxy)-phenyl]-3-thiazol-2-yl-urea (240mg, 76%) be from 4-methyl-2-(3-methyl-butoxy) aniline (193mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：320(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ0.94(d，6H)，1.71(m，2H)，1.85(m，1H)，2.26(s，3H)，4.04(t，2H)，6.70(d，1H)，6.87(s，1H)，7.11(d，1H)，7.36(d，1H)，7.96(d，1H)，8.50(br，1H)，11.26(br，1H).

Embodiment 412

1-(2-allyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-allyloxy-4-nitrotoluene (0.67g, 70%) is that (0.77g is 5.0mmol) according to common processes G preparation from vinylcarbinol and 3-fluoro-4-nitrotoluene.According to common processes B, it is reduced to 4-methyl-2-(allyloxy) aniline (0.40g, 70%).1-(2-allyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (196mg, 68%) be from 4-methyl-2-(2-methyl propoxy-) aniline (163mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：290(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ2.25(s，3H)，4.64(d，2H)，5.30(m，1H)，5.49(m，1H)，6.09(m，1H)，6.74(dd，1H)，6.87(s，1H)，7.10(d，1H)，7.36(dd，1H)，7.97(d，1H)，8.60(br，1H)，11.15(br，1H).

Embodiment 4l3

1-[4-methyl-2-(2-methyl-allyloxy)-phenyl]-3-thiazol-2-yl-urea

3-(2-methyl-allyloxy)-4-nitrotoluene (0.78g, 75%) is that (0.77g 5.0mmo1) prepares according to common processes G from the pure and mild 3-fluoro-of methylallyl 4-nitrotoluene.According to common processes B, it is reduced to 4-methyl-2-(2-methyl-allyloxy) aniline (0.47g, 70%).1-[4-methyl-2-(2-methyl-allyloxy)-phenyl]-3-thiazol-2-yl-urea (210mg, 70%) be from 4-methyl-2-(2-methyl-allyloxy) aniline (179mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：304(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.83(s，3H)，2.25(s，3H)，4.54(s，2H)，5.00(s，1H)，5.15(s，1H)，6.72(d，1H)，6.86(s，1H)，7.10(d，1H)，7.36(d，1H)，7.97(d，1H)，8.60(br，1H)，11.21(br，1H).

Embodiment 414

1-[4-methyl-2-(3-methyl-but-2-ene oxygen base)-phenyl]-3-thiazol-2-yl-urea

3-(3-methyl-but-2-ene oxygen base)-4-nitrotoluene (0.8g, 72%) is that (0.77g 5.0mmol) prepares according to common processes G from the pure and mild 3-fluoro-of 3-methyl but-2-ene-1-4-nitrotoluene.According to common processes B, it is reduced to 4-methyl-2-(3-methyl-but-2-ene oxygen base) aniline (0.43g, 62%).1-[4-methyl-2-(3-methyl-but-2-ene oxygen base)-phenyl]-3-thiazol-2-yl-urea (206mg, 65%) be from 4-methyl-2-(3-methyl-but-2-ene oxygen base) aniline (191mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：318(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.75(d，6H)，2.25(s，3H)，4.60(d，2H)，5.26(t，1H)，6.71(d，1H)，6.89(s，1H)，7.09(d，1H)，7.35(d，1H)，7.96(dd，1H)，8.56(br，1H)，11.17(br，1H).

Embodiment 415

1-(2-isopropoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-(2-isopropoxy)-4-nitrotoluene (0.72g, 74%) is that (0.77g is 5.0mmol) according to common processes G preparation from 2-propyl alcohol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 2-isopropoxy-4-methyl-aniline (0.42g, 70%).1-(2-isopropoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (180mg, 62%) be from 2-isopropoxy-4-methyl-aniline (165mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：292(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.32(d，6H)，2.24(s，3H)，4.63(m，1H)，6.70(dd，1H)，6.88(d，1H)，7.10(d，1H)，7.37(d，1H)，7.97(d，1H)，8.60(br，1H)，11.27(br，1H).

Embodiment 416

1-(2-cyclopentyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-cyclopentyloxy-4-nitrotoluene (0.68g, 62%) is that (0.77g is 5.0mmol) according to common processes G preparation from cyclopentanol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 2-cyclopentyloxy-4-methyl-aniline (0.43g, 70%).1-(2-cyclopentyloxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (220mg, 70%) be from 2-cyclopentyloxy-4-methyl-aniline (191mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：318(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.60(m，2H)，1.80(m，4H)，1.93(m，2H)，2.25(s，3H)，4.86(m，1H)，6.68(dd，1H)，6.81(d，1H)，7.10(d，1H)，7.37(d，1H)，7.97(d，1H)，8.40(br，1H)，11.31(br，1H).

Embodiment 417

1-(2-cyclo propyl methoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-cyclo propyl methoxy-4-nitrotoluene (0.77g, 75%) is that (0.77g is 5.0mmol) according to common processes G preparation from cyclopropyl-carbinol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 2-cyclo propyl methoxy-4-methyl-aniline (0.47g, 71%).1-(2-cyclo propyl methoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (218mg, 72%) be from 2-cyclo propyl methoxy-4-methyl-aniline (177mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：304(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ0.37(m，2H)，0.59(m，2H)，1.29(m，1H)，2.24(s，3H)，3.88(d，2H)，6.71(d，1H)，6.84(d，1H)，7.10(d，1H)，7.37(d，1H)，7.96(d，1H)，8.60(br，1H)，11.25(br，1H).

Embodiment 418

1-[4-methyl-2-(tetrahydrochysene-pyrans-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea

4-nitro-3-(tetrahydrochysene-pyrans-2-ylmethoxy)-toluene (0.80g, 64%) is that (0.77g is 5.0mmol) according to common processes G preparation from tetrahydropyrans-2-base methyl alcohol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 4-methyl-2-(tetrahydrochysene-pyrans-2-ylmethoxy)-aniline (0.50g, 71%).1-[4-methyl-2-(tetrahydrochysene-pyrans-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea (246mg, 71%) be from 4-methyl-2-(tetrahydrochysene-pyrans-2-ylmethoxy)-aniline (221mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：348(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.34(m，1H)，1.50(m，2H)，1.55(m，1H)，1.75(d，1H)，1.83(m，1H)，2.25(s，3H)，3.43(m，1H)，3.90(m，2H)，4.01(m，1H)，6.72(d，1H)，6.86(d，1H)，7.10(d，1H)，7.37(d，1H)，7.96(d，1H)，8.50(br，1H)，11.28(br，1H).

Embodiment 419

1-[4-methyl-2-(tetrahydrochysene-furans-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea

4-nitro-3-(tetrahydrochysene-furans-2-ylmethoxy)-toluene (0.88g, 75%) is that (0.77g is 5.0mmol) according to common processes G preparation from tetrahydrochysene-furans-2-base methyl alcohol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 4-methyl-2-(tetrahydrochysene-furans-2-ylmethoxy)-aniline (0.50g, 65%).1-[4-methyl-2-(tetrahydrochysene-furans-2-ylmethoxy)-phenyl]-3-thiazol-2-yl-urea (236mg, 71%) be from 4-methyl-2-(tetrahydrochysene-furans-2-ylmethoxy)-aniline (207mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：334(M+1) ⁺.

Embodiment 420

1-(2-cyclopentyl methoxyl group-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-cyclopentyl methoxyl group-4-nitrotoluene (0.82g, 70%) is that (0.77g is 5.0mmol) according to common processes G preparation from cyclopentyl carbinol and 3-fluoro-4-nitrotoluene.According to common processes C, it is reduced to 2-cyclopentyl methoxyl group-4-methyl-aniline (0.58g, 81%).1-(2-cyclopentyl methoxyl group-4-methyl-phenyl)-3-thiazol-2-yl-urea (225mg, 68%) be from 2-cyclopentyl methoxyl group-4-methyl-aniline (205mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：332(M+1) ⁺；

Embodiment 421

2-[3-(2-cyclo propyl methoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl)-acetic acid

2-[3-(2-cyclo propyl methoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (253mg, 65%) be from 2-cyclo propyl methoxy-4-methyl-aniline (177mg, 1.0mmol) and (2-amino-thiazolyl--4-yl)-acetic acid ethyl ester (186mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：390(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.36(m，2H)，0.59(m，2H)，1.18(t，3H)，1.28(m，1H)，2.24(s，3H)，3.64(s，2H)，3.88(d，2H)，4.08(q，2H)，6.71(dd，1H)，6.83(d，1H)，6.86(d，1H)，7.94(d，1H)，8.40(br，1H)，11.36(br，1H).

2-[3-(2-cyclo propyl methoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (165mg, 92%) be that (195mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-cyclo propyl methoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS(m/z)：362(M+1) ⁺.

Embodiment 422

2-[3-(2-cyclopentyloxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(2-cyclopentyloxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (250mg, 62%) be from 2-cyclopentyloxy-4-methyl-aniline (191mg, 1.0mmol) and (2-amino-thiazolyl--4-yl)-acetic acid ethyl ester (186mg is 1.0mmol) according to common processes D preparation.2-[3-(2-cyclopentyloxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (170mg, 91%) be that (200mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-cyclo propyl methoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

LC-MS(m/z)：376(M+1) ⁺.

Embodiment 423

1-(2-isobutoxy-4-methylsulfonyl methyl-phenyl)-3-thiazol-2-yl-urea

2-isobutoxy-4-methylsulfonyl methyl isophthalic acid-nitro-benzene (0.93g, 65%) is that (1.16g is 5.0mmol) according to common processes G preparation from 2-methylpropanol and 2-fluoro-4-methylsulfonyl methyl isophthalic acid-nitro-benzene.According to common processes B, it is reduced to 2-isobutoxy-4-methylsulfonyl methyl-aniline (0.46g, 56%).1-(2-isobutoxy-4-methylsulfonyl methyl-phenyl)-3-thiazol-2-yl-urea (250mg; 65%) be from 2-isobutoxy-4-methylsulfonyl methyl-aniline (257mg; 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：384(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.06(d，6H)，2.14(m，1H)，2.88(s，3H)，3.11(s，2H)，4.39(d，2H)，6.19(s，1H)，6.89(d，1H)，7.14(s，1H)，7.39(d，1H)，8.13(d，1H)，8.50(br，1H)，11.24(br，1H).

Embodiment 424

(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-kharophen)-acetic acid

(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-kharophen)-acetic acid (90mg, 86%) be from (2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl-kharophen)-(108mg is 0.25mmol) according to common processes J preparation for the acetic acid methyl ester.(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-kharophen)-acetic acid methyl ester (150mg, 70%) be then from { 2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (181mg, 0.5mmol) and glycine methyl ester hydrochloride according to common processes K preparation.

LC-MS(m/z)：421(M+1) ⁺.

Embodiment 425

1-(5-formyl radical-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea

4-(2-methyl propoxy-)-3-nitrobenzaldehyde (0.83g, 75%) is that (0.46mL, 5.0mmol) (0.77g 5.0mmol) prepares according to common processes G with 4-fluoro-3-nitrobenzaldehyde from the 2-methylpropanol.According to common processes B, it is reduced to 5-formyl radical-2-(2-methyl propoxy-)-aniline (0.49g, 68%).1-(5-formyl radical-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea (208mg, 65%) be from 5-formyl radical-2-(2-methyl propoxy-) aniline (193mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：320(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.06(d，6H)，2.16(m，1H)，3.96(d，2H)，7.16(d，1H)，7.25(d，1H)，7.40(dd，1H)，7.61(d，1H)，8.69(s，1H)，9.86(s，1H)，10.75(br，1H)，11.51(br，1H).

Embodiment 426

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(2-methoxyl group-ethyl)-ethanamide

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(2-methoxyl group-ethyl)-ethanamide (130mg, 62%) be from { 2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (181mg, 0.5mmol) and the 2-methoxyethyl amine according to common processes K preparation.

LC-MS(m/z)：421(M+1) ⁺.

Embodiment 427

1-(5-fluoro-2-isobutoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-fluoro-5-(2-methyl propoxy-)-4-nitrotoluene (0.73g, 65%) is that (0.46mL, 5.0mmol) with 2, (0.86g 5.0mmol) prepares according to common processes G 5-two fluoro-4-nitrotoluenes from the 2-methylpropanol.According to common processes C, it is reduced to 5-fluoro-4-methyl-2-(2-methyl propoxy-)-aniline (0.45g, 70%).1-(5-fluoro-2-isobutoxy-4-methyl-phenyl)-3-thiazol-2-yl-urea (205mg, 64%) be from 5-fluoro-4-methyl-2-(2-methyl propoxy-)-aniline (197mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：324(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.03(d，6H)，2.16(m，1H)，2.17(s，3H)，3.80(d，2H)，6.92(d，1H)，7.14(d，1H)，7.38(d，1H)，7.93(d，1H)，8.50(br，1H)，11.44(br，1H).

Embodiment 428

1-(5-fluoro-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea

5-fluoro-2-(2-methyl propoxy-)-4-oil of mirbane (0.83g, 78%) is that (0.46mL, 5.0mmol) with 2, (0.80g 5.0mmol) prepares according to common processes G 5-two fluoro-4-oil of mirbane from the 2-methylpropanol.According to common processes C, it is reduced to 5-fluoro-2-(2-methyl propoxy-)-aniline (0.58g, 81%).1-(5-fluoro-2-isobutoxy-phenyl)-3-thiazol-2-yl-urea (220mg, 72%) be from 5-fluoro-2-(2-methyl propoxy-)-aniline (183mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：310(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.03(d，6H)，2.11(m，1H)，3.80(d，2H)，6.79(m，1H)，6.99(m，1H)，7.15(d，1H)，7.39(d，1H)，8.01(dd，1H)，8.60(br，1H)，11.52(br，1H).

Embodiment 429

1-(2-isobutyl sulfenyl-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-(isobutyl sulfenyl)-4-nitrotoluene (0.75g, 67%) is that (0.77g is 5.0mmol) according to common processes A preparation from 2-methyl-prop mercaptan and 3-fluoro-4-nitrotoluene.According to common processes B, it is reduced to 2-isobutyl sulfenyl-4-methyl-aniline (0.46g, 63%).1-(2-isobutyl sulfenyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (218mg, 68%) be from 2-isobutyl sulfenyl-4-methyl-aniline (195mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：318(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.85(m，6H)，1.40(m，1H)，2.26(s，3H)，2.80(m，2H)，7.11(s，1H)，7.29(s，1H)，7.38(d，1H)，7.89(d，1H)，8.65(br，1H)，11.28(br，1H).

Embodiment 430

2-[3-(2-isobutyl sulfenyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(2-isobutyl sulfenyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (276mg, 68%) be from 2-isobutyl sulfenyl-4-methyl-aniline (195mg, 1.0mmol) and ethyl 2-amino-4-thiazolyl acetate (186mg is 1.0mmol) according to common processes D preparation.According to this ester of common processes J hydrolysis, obtain 2-[3-(2-isobutyl sulfenyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (230mg, 90%).

LC-MS(m/z)：380(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.85(m，6H)，1.49(m，1H)，2.26(s，3H)，2.83(m，2H)，3.56(s，2H)，6.85(s，1H)，7.09(d，1H)，7.29(d，1H)，7.89(d，1H)，8.65(br，1H)，11.28(br，2H).

Embodiment 431

1-(2-pentamethylene sulfinyl-4-methyl-phenyl)-3-thiazol-2-yl-urea

According to common processes R, (0.47g 2.0mmol) is oxidized to 3-pentamethylene sulfinyl-4-nitrotoluene (0.46g, 91%) (use-equivalent m-cpba) with 3-pentamethylene sulfenyl-4-nitrotoluene.According to common processes C, 3-pentamethylene sulfinyl-4-nitrotoluene is reduced to 2-pentamethylene sulfinyl-4-methyl-aniline (0.33g, 81%).1-(2-pentamethylene sulfinyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (225mg, 65%) be from 2-pentamethylene sulfinyl-4-methyl-aniline (223mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：350(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.58(m，6H)，1.78(m，1H)，1.94(m，1H)，2.34(s，3H)，3.43(m，1H)，7.11(d，1H)，7.33(dd，1H)，7.36(dd，1H)，7.43(s，1H)，7.80(d，1H)，8.93(br，1H)，11.25(br，1H).

Embodiment 432

1-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-3-thiazol-2-yl-urea

3-pentamethylene sulfenyl-4-nitrotoluene (0.83g, 70%) is that (0.77g is 5.0mmol) according to common processes A preparation from cyclopentyl mercaptan and 3-fluoro-4-nitrotoluene.According to common processes R, it is oxidized to 3-pentamethylene alkylsulfonyl-4-nitrotoluene (0.84g, 90%).According to common processes C, 3-pentamethylene alkylsulfonyl-4-nitrotoluene is reduced to 2-pentamethylene alkylsulfonyl-4-methyl-aniline (0.53g, 70%).1-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-3-thiazol-2-yl-urea (225mg, 62%) be from 2-pentamethylene alkylsulfonyl-4-methyl-aniline (239mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：366(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.58(m，2H)，1.78(m，2H)，1.86(m，2H)，2.04(m，2H)，2.38(s，3H)，3.54(m，1H)，6.94(d，1H)，7.43(dd，1H)，7.61(d，1H)，7.67(d，1H)，8.18(d，1H)，9.20(br，1H)，11.25(br，1H).

Embodiment 433

2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (305mg; 68%) be from 2-pentamethylene alkylsulfonyl-4-methyl-aniline (239mg; 1.0mmol) and ethyl 2-amino-4-thiazolyl acetate (186mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：452(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.19(t，3H)，1.58(m，4H)，1.84(m，4H)，2.35(s，3H)，3.65(s，2H)，3.77(m，1H)，4.08(q，2H)，6.91(s，1H)，7.52(d，1H)，7.63(s，1H)，8.00(d，1H)，8.91(br，1H)，11.89(br，1H).

Embodiment 434

2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

According to common processes J; hydrolysis 2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (225mg; 0.5mmol), obtain 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid (193mg, 92%).

LC-MS(m/z)：424(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.60(m，4H)，1.84(m，4H)，2.36(s，3H)，3.57(s，2H)，3.77(m，1H)，6.87(s，1H)，7.52(d，1H)，7.63(s，1H)，8.01(d，1H)，8.95(br，1H)，12.32(br，2H).

Embodiment 435

2-{2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide

2-{2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide (30mg; 68%) be from { 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid (42mg, 0.1mmol) and methylamine according to common processes K preparation.

LC-MS(m/z)：437(M+1) ⁺.

Embodiment 436

2-{2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-(2-methoxyl group-ethyl)-ethanamide

2-{2-[3-(2-pentamethylene alkylsulfonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-N-methyl-ethanamide (30mg; 68%) be from { 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid (42mg, 0.1mmol) and the 2-methoxyethyl amine according to common processes K preparation.

LC-MS(m/z)：480(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.60(m，4H)，1.84(m，4H)，2.36(s，3H)，3.21(m，4H)，3.24(s，3H)，3.43(s，2H)，3.76(m，1H)，6.81(s，1H)，7.52(d，1H)，7.63(s，1H)，8.05(br，2H)，8.95(br，1H)，11.85(br，1H).

Embodiment 437

1-(2-cyclopentyl amino-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-cyclopentyl amino-4-methyl-aniline (0.64g, 68%) is that (1.0mL, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from cyclopentyl amine.1-(2-cyclopentyl amino-4-methyl-phenyl)-3-thiazol-2-yl-urea (195mg, 62%) be from 2-cyclopentyl amino-4-methyl-aniline (190mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：317(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ1.46(m，2H)，1.59(m，2H)，1.68(m，2H)，2.01(m，2H)，2.32(s，3H)，3.78(m，1H)，6.51(d，1H)，6.56(s，1H)，6.88(d，1H)，7.07(br，1H)，7.31(d，1H)，9.30(br，1H)，10.72(br，1H).

Embodiment 438

1-(2-isobutylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-isobutylamino-4-methyl-aniline (0.61g, 69%) is that (0.73g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from isobutylamine.1-(2-isobutylamino-4-methyl-phenyl)-3-thiazol-2-yl-urea (196mg, 65%) be from 2-isobutylamino-4-methyl-aniline (178mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：305(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ0.95(d，6H)，1.88(m，1H)，2.31(s，3H)，2.92(d，2H)，4.15(br，1H)，6.51(m，2H)，6.87(d，1H)，7.08(m，1H)，7.31(d，1H)，9.30(br，1H)，10.72(br，1H).

Embodiment 439

1-[4-methyl-2-(methyl-propyl group-amino)-phenyl]-3-thiazol-2-yl-urea

4-methyl-2-(methyl-propyl group-amino)-aniline (0.56g, 63%) is that (0.73g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from N-methyl-propyl group amine.1-[4-methyl-2-(methyl-propyl group-amino)-phenyl]-3-thiazol-2-yl-urea (215mg, 71%) be from 4-methyl-2-(methyl-propyl group-amino)-aniline (178mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：305(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.85(t，3H)，1.40(m，2H)，2.24(s，3H)，2.54(s，3H)，2.79(t，2H)，6.87(dd，1H)，7.02(d，1H)，7.09(d，1H)，7.37(d，1H)，7.99(d，1H)，8.80(br，1H)，11.36(br，1H).

Embodiment 440

1-[2-(butyl-methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea

4-methyl-2-(butyl-methyl-amino)-aniline (0.62g, 65%) is that (0.87g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from N-methyl-butylamine.1-[2-(butyl-methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea (220mg, 69%) be from 4-methyl-2-(butyl-methyl-amino)-aniline (192mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：319(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.82(t，3H)，1.27(m，2H)，1.38(m，2H)，2.24(s，3H)，2.54(s，3H)，2.82(t，2H)，6.87(d，1H)，7.02(s，1H)，7.09(d，1H)，7.37(d，1H)，7.97(d，1H)，8.80(br，1H)，11.37(br，1H).

Embodiment 441

1-(2-diethylin-4-methyl-phenyl)-3-thiazol-2-yl-urea

2-(diethylin)-4-methyl-aniline (0.63g, 71%) is that (0.73g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from diethylamine.1-(2-diethylin-4-methyl-phenyl)-3-thiazol-2-yl-urea (188mg, 62%) be from 2-(diethylin)-4-methyl-aniline (178mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：305(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.89(t，6H)，2.24(s，3H)，2.90(q，4H)，6.92(dd，1H)，7.04(d，1H)，7.09(d，1H)，7.37(d，1H)，8.04(d，1H)，9.00(br，1H)，11.44(br，1H).

Embodiment 442

1-[2-(cyclopropyl methyl-propyl group-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea

2-(cyclopropyl methyl-propyl group-amino)-4-methyl-aniline (0.68g, 63%) is that (1.13g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from N-propyl-cyclopropane methylamine.1-[4-methyl-2-(methyl-propyl group-amino)-phenyl]-3-thiazol-2-yl-urea (210mg, 61%) be from 4-methyl-2-(methyl-propyl group-amino)-aniline (218mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：345(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ-0.24(m，2H)，0.30(m，2H)，0.80(m，4H)，1.32(m，2H)，2.24(s，3H)，2.69(d，2H)，2.91(t，2H)，6.90(dd，1H)，7.07(m，2H)，7.37(d，1H)，8.01(m，1H)，9.00(br，1H)，11.51(br，1H).

Embodiment 443

1-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea

2-(isobutyl--methyl-amino)-4-methyl-aniline (0.62g, 65%) is that (0.87g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from N-isobutyl--methylamine.1-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-3-thiazol-2-yl-urea (216mg, 68%) be from 2-(isobutyl--methyl-amino)-4-methyl-aniline (192mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：319(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ0.86(d，6H)，1.68(m，1H)，2.31(s，3H)，2.58(s，3H)，2.66(d，2H)，6.88(d，1H)，6.96(m，2H)，7.44(d，1H)，8.12(d，1H)，9.20(br，1H)，11.36(br，1H).

Embodiment 444

(2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-the acetic acid ethyl ester

(2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid ethyl ester (290mg, 72%) be from 2-(isobutyl--methyl-amino)-4-methyl-aniline (192mg, 1.0mmol) and ethyl 2-amino-4-thiazolyl acetate (186mg is 1.0mmol) according to common processes D preparation.According to this ester of common processes J hydrolysis, obtain (2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid (250mg, 92%).

LC-MS(m/z)：377(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ0.85(d，6H)，1.60(m，1H)，2.21(s，3H)，2.66(m，5H)，3.53(s，2H)，6.81(s，1H)，6.85(d，1H)，6.99(s，1H)，7.95(d，1H)，8.60(br，1H)，11.55(br，1H)，12.35(br，1H).

Embodiment 445

2-(2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide

2-(2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-methyl-ethanamide (63mg, 65%) be from (2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups-thiazole-4-yl)-acetic acid (95mg, 0.25mmol) and methylamine according to common processes K preparation.

LC-MS(m/z)：390(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ0.85(d，6H)，1.67(m，1H)，2.29(s，3H)，2.63(s，3H)，2.75(s，2H)，2.80(s，3H)，3.62(s，2H)，6.50(br，1H)，6.62(s，1H)，6.93(m，2H)，8.04(d，1H)，8.68(br，1H)，10.00(br，1H).

Embodiment 446

2-(2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-(2-methoxyl group-ethyl)-ethanamide

2-(2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-N-(2-methoxyl group-ethyl)-ethanamide (78mg, 72%) be from (2-{3-[2-(isobutyl--methyl-amino)-4-methyl-phenyl]-urea groups-thiazole-4-yl)-acetic acid (95mg, 0.25mmol) and 2-methoxyl group methylamine according to common processes K preparation.

LC-MS(m/z)：434(M+1) ⁺.

Embodiment 447

1-(4-methyl-2-tetramethyleneimine-1-base-phenyl)-3-thiazol-2-yl-urea

4-methyl-2-(tetramethyleneimine-1-yl) aniline (0.57g, 65%) is that (0.71g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from tetramethyleneimine.1-(4-methyl-2-tetramethyleneimine-1-base-phenyl)-3-thiazol-2-yl-urea (217mg, 72%) be from 4-methyl-2-(tetramethyleneimine-1-yl) aniline (176mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：303(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ1.89(m，4H)，2.23(s，3H)，3.02(m，4H)，6.75(dd，1H)，6.88(d，1H)，7.09(d，1H)，7.36(dd，1H)，7.70(d，1H)，8.40(br，1H)，11.07(br，1H).

Embodiment 4481-[2-(2,3-dihydro-indoles-1-yl)-5-fluoro-phenyl]-3-thiazol-2-yl-urea

2-(2,3-dihydro-indoles-1-yl)-5-fluoro-aniline (0.59g, 52%) is that (0.6g, 5.0mmol) with 2, (0.80g 5.0mmol) prepares according to common processes W 5-two fluoro-oil of mirbane from indoline.1-[2-(2,3-dihydro-indoles-1-yl)-5-fluoro-phenyl]-3-thiazol-2-yl-urea (198mg, 56%) is from 2-(2,3-dihydro-indoles-1-yl)-5-fluoro-aniline (228mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：355(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ3.16(t，2H)，3.70(br，2H)，6.10(d，1H)，6.73(m，1H)，6.94(m，2H)，7.14(d，1H)，7.22(d，1H)，7.34(m，2H)，8.13(dd，1H)，9.01(br，1H)，11.32(br，1H).

Embodiment 449

1-(4-methyl-2-piperidines-1-base-phenyl)-3-thiazol-2-yl-urea

4-methyl-2-(piperidines-1-yl)-aniline (0.63g, 67%) is that (0.85g, 10.0mmol) (0.77g 5.0mmol) prepares according to common processes W with 3-fluoro-4-nitrotoluene from piperidines.1-(4-methyl-2-piperidines-1-base-phenyl)-3-thiazol-2-yl-urea (214mg, 68%) be from 4-methyl-2-(piperidines-1-yl)-aniline (190mg, 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：317(M+1) ⁺， ¹H?NMR(400MHz，CDCl ₃)：δ1.49(m，2H)，1.69(m，4H)，2.30(s，3H)，2.82(t，4H)，6.92(m，3H)，7.47(d，1H)，7.96(d，1H)，8.90(br，1H)，11.36(br，1H).

Embodiment 450

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (285mg, 71%) be from 4-methyl-2-(piperidines-1-yl)-aniline (190mg, 1.0mmol) and ethyl 2-amino-4-thiazolyl acetate (186mg is 1.0mmol) according to common processes D preparation.According to this ester of common processes J hydrolysis, obtain 2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (238mg, 90%).

LC-MS(m/z)：375(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ1.53(br，2H)，1.75(m，4H)，2.23(s，3H)，2.70(m，4H)，3.55(s，2H)，6.83(s，1H)，6.87(d，1H)，6.99(s，1H)，7.92(d，1H)，8.40(br，1H)，11.28(br，1H)，12.42(br，1H).

Embodiment 451

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-methyl-phenyl]-3-thiazol-2-yl-urea

3-(2-fluoro-6-methoxyl group phenoxy group)-nitrotoluene (0.9g, 65%) is that (0.78g, 5.5mmol) (0.77g 5.0mmol) prepares according to common processes A with 3-fluoro-4-nitrotoluene from 2-fluoro-6-methoxyphenol.According to common processes C, this compound is reduced to 4-fluoro-2-(2-fluoro-6-methoxyl group phenoxy group) aniline (0.58g, 72%).1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-methyl-phenyl]-3-thiazol-2-yl-urea (122mg, 65%) be from 2-(2-fluoro-6-methoxyl group-phenoxy group)-4-methyl-aniline (124mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LCMS(m/z)：374(M+2) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ2.13(s，3H)，3.79(s，3H)，6.30(s，1H)，6.83(d，1H)，7.07(m，3H)，7.34(m，2H)，8.06(d，1H)，8.97(br，1H)，10.93(s，1H).

Embodiment 452

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-(4-methyl-piperazine-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea

With 3-(2-fluoro-6-methoxyl group phenoxy group)-nitrotoluene (0.28g, 1.0mmol) and N-bromine succinimide (200mg is 1.1mmol) with the CCl of dibenzoyl peroxide (10mg) ₄(10mL) solution heats 3h down at 90 ℃.With the reaction mixture cooling, filter concentrated filtrate.(110mg, THF 1.1mmol) (5mL) solution heat 4h with mixture down at 60 ℃ to add N methyl piperazine to resistates.Under reduced pressure remove volatile matter.Resistates is dissolved in ethyl acetate, washing (salt solution), dry (Na ₂SO ₄), concentrate.According to common processes C, be 2-(2-fluoro-6-methoxyl group-phenoxy group)-4-(4-methyl-piperazine-1-ylmethyl)-aniline (224mg, 65%) with the gained nitrobenzene reduction.1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-(4-methyl-piperazine-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea (130mg, 55%) be from 2-(2-fluoro-6-methoxyl group-phenoxy group)-4-(4-methyl-piperazine-1-ylmethyl)-aniline (172mg, 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LCMS(m/z)：472(M+2) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ2.12(s，3H)，2.24(br，8H)，3.28(s，2H)，3.77(s，3H)，6.46(s，1H)，6.89(d，1H)，7.07(m，3H)，7.34(m，2H)，8.11(d，1H)，9.02(br，1H)，10.96(s，1H).

Embodiment 453

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid

(2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid ethyl ester (330mg, 72%) be from 2-(2-fluoro-6-methoxyl group phenoxy group)-aniline (247mg, 1.0mmol) and ethyl 2-amino-4-thiazolyl acetate (186mg is 1.0mmol) according to common processes D preparation.According to this ester of common processes J hydrolysis, obtain (2-{3-[2-(2-fluoro-6-methoxyl group-phenoxy group)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid (283mg, 91%).

LCMS(m/z)：432(M+2) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ2.13(s，3H)，3.55(s，2H)，3.79(s，3H)，6.30(s，1H)，6.83(d，1H)，6.88(s，1H)，7.03(m，2H)，7.34(m，1H)，8.04(d，1H)，9.05(br，1H)，11.02(br，2H).

Embodiment 454

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-formyl radical-phenyl]-3-thiazol-2-yl-urea

4-(2-fluoro-6-methoxyl group-phenoxy group)-3-nitrobenzaldehyde (1.0g, 70%) is that (0.78g, 5.5mmol) (0.84g 5.0mmol) prepares according to common processes A with 4-fluoro-3-nitrobenzaldehyde from 2-fluoro-6-methoxyphenol.According to common processes B, it is reduced to 5-formyl radical-2-(2-fluoro-6-methoxyl group-phenoxy group)-aniline (0.57g, 62%).1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-formyl radical-phenyl]-3-thiazol-2-yl-urea (265mg; 69%) be from 5-formyl radical-2-(2-fluoro-6-methoxyl group-phenoxy group)-aniline (261mg; 1.0mmol) and thiazolamine (100mg is 1.0mmol) according to common processes D preparation.

LC-MS(m/z)：388(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ3.80(s，3H)，6.71(d，1H)，7.14(m，3H)，7.39(m，2H)，7.52(dd，1H)，8.78(d，1H)，9.31(br，1H)，9.90(s，1H)，11.04(s，1H).

Embodiment 455

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-morpholine-4-ylmethyl-phenyl]-3-thiazol-2-yl-urea

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-morpholine-4-ylmethyl-phenyl]-3-thiazol-2-yl-urea (35mg; 78%) be from 1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-formyl radical-phenyl]-3-thiazol-2-yl-urea (39mg, 0.1mmol) and morpholine according to common processes O preparation.

LC-MS(m/z)：459(M+1) ⁺， ¹H?NMR(400MHz，DMSO-d ₆)：δ2.24(s，4H)，3.30(s，2H)，3.48(s，4H)，3.77(s，3H)，6.48(s，1H)，6.93(d，1H)，7.10(m，3H)，7.37(m，2H)，8.12(d，1H)，9.04(br，1H)，10.96(br，1H).

Embodiment 456

1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methylsulfonyl methyl-phenyl]-3-thiazol-2-yl-urea

With 4-(2-fluoro-6-methoxyl group phenoxy group)-3-nitrotoluene (0.28g, 1.0mmol) and N-bromine succinimide (200mg is 1.1mmol) with the CCl of dibenzoyl peroxide (10mg) ₄(10mL) solution heats 3h down at 90 ℃.With the reaction mixture cooling, filter concentrated filtrate.(110mg, THF 1.1mmol) (5mL) solution heat 4h with mixture down at 60 ℃ to add methyl-sulfinic acid sodium to this resistates.Under reduced pressure remove volatile matter.Resistates is dissolved in ethyl acetate, washing (salt solution), dry (Na ₂SO ₄), concentrate.According to common processes B, be 2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methylsulfonyl methyl-aniline (210mg, 65%) with the gained nitrobenzene reduction.1-[2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methylsulfonyl methyl-phenyl]-3-thiazol-2-yl-urea (138mg; 61%) be from 2-(2-fluoro-6-methoxyl group-phenoxy group)-5-methylsulfonyl methyl-aniline (162mg; 0.5mmol) and thiazolamine (60mg is 0.6mmol) according to common processes D preparation.

LCMS(m/z)：452(M+1) ⁺； ¹H?NMR(400MHz，DMSO-d ₆)：δ2.93(s，3H)，3.35(s，2H)，3.80(s，3H)，6.52(d，1H)，6.93(d，1H)，7.07(m，3H)，7.35(m，2H)，8.31(s，1H)，9.22(br，1H)，11.02(s，1H).

Embodiment 457

5-chloro-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

To 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester (0.05g, and 2mL acetonitrile solution adding N-chloro-succinimide 0.12mmol) (0.018g, 0.13mmol).In the pressure bottle of lucifuge, reaction mixture was stirred 1.5 hours under nitrogen at 80 ℃.Mixture with 15mL DCM dilution, is washed (1N HCl, saturated NaHCO ₃, water), dry (MgSO ₄), under reduced pressure concentrate.Crude product obtains title compound (0.08g, 15%) through the preparation HPLC purifying.

HPLC-MS (method A): m/z=450,452 (M+1) ⁺Rt=5.55min.

¹H NMR (300MHz, CDCl ₃): δ 1.29 (t, J=7.2Hz, 3H), 1.71 (m, 4H), 1.90 (m, 4H), 2.37 (s, 3H), 3.70 (s, 2H), 3.75 (m, 1H), 4.24 (q, J=7.2Hz, 2H), 7.35 (d, J=7.9Hz, 1H), 7.70 (s, 1H), 8.42 (d, J=8.3Hz, 1H) and 11.59 (s, 1H)

Embodiment 458

5-bromo-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

To 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester (0.05g, and 2mL acetonitrile solution adding N-bromine succinimide 0.12mmol) (0.024g, 0.13mmol).In the pressure bottle of lucifuge, reaction mixture stirred under nitrogen at 25 ℃ spend the night.Mixture with 15mL DCM dilution, is washed (1N HCl, saturated NaHCO ₃, water), dry (MgSO ₄), under reduced pressure concentrate.Crude product obtains title compound (0.013g, 21%) through the preparation HPLC purifying.

HPLC-MS (method A): m/z=494,496 (M+1) ⁺Rt=5.45min.

¹H NMR (300MHz, CDCl ₃): δ 1.29 (t, J=7.2Hz, 3H), 1.71 (m, 4H), 1.92 (m, 4H), 2.38 (s, 3H), 3.73 (s, 2H), 3.77 (m, 1H), 4.23 (q, J=7.2Hz, 2H), 7.36 (dd, J=1.3,8.5Hz, 1H), 7.73 (s, 1H), 8.37 (d, J=8.3Hz, 1H) and 11.81 (s, 1H).

Embodiment 459

5-chloro-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

To 2-[3-{2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid (0.50g, and 20mL acetonitrile suspension adding N-chloro-succinimide 1.29mmol) (0.19g, 1.42mmol).In the pressure bottle of lucifuge, reaction mixture is stirred 2h at 80 ℃ under nitrogen.Mixture is under reduced pressure concentrated, be dissolved in DMSO, through the preparation HPLC purifying, obtain title compound (0.128g, 24%).

HPLC-MS (method A): m/z=422,424 (M+1) ⁺Rt=5.84min.

¹H NMR (300MHz, DMSO-d ₆): δ 1.64 (m, 4H), 1.77 (m, 2H), 1.90 (m, 2H), 1.90 (m, 2H), 2.34 (s, 3H), 3.56 (s, 2H), 3.88 (m, 1H), 7.40 (dd, J=1.5,8.7Hz, 1H), 7.86 (d, J=1.1Hz, 1H), 8.15 (d, J=8.3Hz, 1H) and 10.69 (s, 1H)

Embodiment 460

5-bromo-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

To 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester (0.20g, and 10mL acetic acid suspension adding N-bromine succinimide 0.52mmol) (0.10g, 0.57mmol).In the pressure bottle of lucifuge, reaction mixture stirred under nitrogen at 25 ℃ spend the night.Mixture is under reduced pressure concentrated, be dissolved in DMSO, through the preparation HPLC purifying, obtain title compound (0.137g, 57%).

HPLC-MS (method A): m/z=466,468 (M+1) ⁺Rt=4.59min.

¹H NMR (300MHz, DMSO-d ₆): δ 1.64 (M, 4H), 1.76 (m, 2H), 1.89 (m, 2H), 2.34 (s, 3H), 3.55 (s, 2H), 3.88 (m, 1H), 7.40 (d, J=8.3Hz, 1H), 7.87 (s, 1H), 8.15 (d, J=8.7Hz, 1H), 10.71 (s, 1H) and 12.15 (s, 1H)

Embodiment 461

Bromo-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

To 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester (0.05g, and 2mL acetonitrile solution adding N-bromine succinimide 0.12mmol) (0.024g, 0.13mmol).In the pressure bottle of lucifuge, reaction mixture stirred under nitrogen at 25 ℃ spend the night.Mixture with 15mL DCM dilution, is washed (1N HCl, saturated NaHCO ₃, water), dry (MgSO ₄), under reduced pressure concentrate.Crude product obtains title compound (0.010g, 17%) through the preparation HPLC purifying.

HPLC-MS (method A): m/z=494,496 (M+1) ⁺Rt=5.19min.

¹H NMR (300 MHz, CDCl ₃): δ 1.33 (t, J=7.2Hz, 3H), 1.71 (m, 4H), 1.92 (m, 4H), 2.37 (s, 3H), 3.76 (m, 1H), 4.30 (dq, J=2.3,7.2Hz, 2H), 5.45 (s, 1H), 7.17 (s, 1H), 7.36 (d, J=8.7Hz, 1H), 7.73 (s, 1H), 8.40 (d, J=8.7Hz, 1H) and 11.83 (s, 1H)

Embodiment 462 (common processes D)

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

Under-20 ℃ of nitrogen atmosphere, go through 10min to the phenyl that is stirring-carboxylamine tertiary butyl ester (1.2g, Et 6.2mmol) ₂The pentane solution of O (12mL) solution dropping 1.7M t-BuLi (8.4mL, 14.3mmol).Mixture is stirred down 2.5h at-10 ℃, go through then 5min add Cyclopentane carboxylic acid methoxyl group-methyl-acid amides (1.07g, 6.8mmol).Make mixture be warmed to room temperature, stir other 1h, use moisture NH then ₄The Cl quencher.Separate organic phase, water CH ₂Cl ₂Extraction merges organic phase, and drying concentrates in a vacuum.Crude product is dissolved in CH ₂Cl ₂(18mL) and TFA (6mL), at room temperature stir 2h.Evaporation reaction mixture adds moisture NaHCO in a vacuum ₃To pH7, use CH ₂Cl ₂Extraction.Merge organic phase, drying concentrates in a vacuum, obtains 1.03g (68%) (2-amino-phenyl)-cyclopentyl-ketone, is oil.

Title compound (41mg, 16%) is that (120mg, 0.63mmol) (118mg 0.63mmol) prepares according to common processes D with ethyl 2-amino-4-thiazolyl acetate from 2-amino-phenyl-cyclopentyl-ketone.

¹H?NMR(400MHz；CDCl ₃)：δ1.28(t，3H)，1.66-1.77(m，4H)，1.84-1.96(m，4H)，3.70(s，2H)，3.74(brt，1H)，4.20(q，2H)，6.72(s，1H)，7.10(t，1H)，7.53(t，1H)，7.92(d，1H)，8.57(brs，1H)，11.78(s，1H)；HPLC-MS：m/z＝424.0(M+23)；Rt＝4.45min.

Embodiment 463 (common processes J)

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (9mg, 27%) is that (208mg is 0.5mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H NMR (400MHz; Acetone d ₆): δ 1.85-2.11 (m, 8H), 3.71 (s, 2H), 3.94 (brt, 1H), 6.86 (s, 1H), 7.18 (t, 1H), 7.79 (t, 1H), 8.09 (d, 1H), 8.56 (d, 1H), 11.36 (s, 1H); HPLC-MS:m/z=396.1 (M+23); Rt=3.87min.

Embodiment 464 (common processes AA)

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

At-20 ℃, under nitrogen atmosphere, go through 10min to (4-methoxyl group-phenyl)-carboxylamine tertiary butyl ester (2.0g, Et 9.0mmol) that are stirring ₂The pentane solution of O (20mL) solution dropping 1.7M t-BuLi (12.1mL, 20.6mmol).Mixture is stirred down 1.5h at-15 ℃, go through then 5min add Cyclopentane carboxylic acid methoxyl group-methyl-acid amides (1.55g, 9.9mmol).Make mixture be warmed to room temperature, stir other 1h, use moisture NH then ₄The Cl quencher.Separate organic phase, water CH ₂Cl ₂Extraction merges organic phase, and drying concentrates in a vacuum.Crude product is dissolved in CH ₂Cl ₂(18mL) and TFA (6mL), at room temperature stir 2h.Evaporation reaction mixture adds moisture NaHCO in a vacuum ₃To pH7, use CH ₂Cl ₂Extraction, drying concentrates, and obtains crude product, through purification by flash chromatography (Quad flash 25, EtOAc-heptane 1: 20-＞1: 4).Obtain 0.65g (31%) (2-amino-5-methoxyl group-phenyl)-cyclopentyl-ketone, be oil.

Title compound (158mg, 80%) is that (100mg, 0.46mmol) (85mg 0.46mmol) is equipped with according to the common processes Dutch treatment with ethyl 2-amino-4-thiazolyl acetate from (2-amino-5-methoxyl group-phenyl)-cyclopentyl-ketone.

¹H?NMR(400MHz；CDCl ₃)：δ1.28(t，3H)，1.66-1.74(m，4H)，1.86-1.96(m，4H)，3.68(brt，1H)，3.70(s，2H)，3.84(s，3H)，4.20(q，2H)，6.71(s，1H)，7.10(dd，1H)，7.42(d，1H)，8.45(brs，1H)，9.13(brs，1H)，11.31(brs，1H)；HPLC-MS：m/z＝454.1(M+23)；Rt＝5.48min.

Embodiment 465 (common processes J)

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (92mg, 86%) is that (112mg is 0.26mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.58-1.65(m，4H)，1.70-1.92(m，4H)，3.57(s，2H)，3.82(s，3H)，3.88(brp，1H)，6.84(s，1H)，7.19(dd，1H)，7.44(s，1H)，8.08(d，1H)，10.22(s，1H)，12.05(brs，2H)；HPLC-MS：m/z＝426.1(M+23)；Rt＝4.49min.

Embodiment 466 (common processes AA)

2-[3-(2-cyclopropane carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

At-20 ℃, under nitrogen atmosphere, go through 10min to the right-tolyl-carboxylamine tertiary butyl ester (1.0g, Et 4.8mmol) that are stirring ₂The pentane solution of O (10mL) solution dropping 1.7M t-BuLi (6.5mL, 11.1mmol).Mixture is stirred down 2.5h at-10 ℃, go through then 5min add cyclopropane-carboxylic acid methoxyl group-methyl-acid amides (0.92g, 6.3mmol).Make mixture be warmed to room temperature, stir other 1h, use moisture NH then ₄The Cl quencher.Separate organic phase, water CH ₂Cl ₂Extraction merges organic phase, and drying concentrates in a vacuum.Crude product is dissolved in CH ₂Cl ₂(15mL) and TFA (15mL), at room temperature stir 3h.Evaporation reaction mixture adds moisture NaHCO in a vacuum ₃To pH7, use CH ₂Cl ₂Extraction.Merge organic phase, drying concentrates in a vacuum, obtains thick (2-amino-5-methyl-phenyl)-cyclopropyl-ketone of 0.80g, is the oil of yellow.

Title compound (190mg, 43%) is that (200mg, 1.14mmol) (212mg 1.14mmol) is equipped with according to the common processes Dutch treatment with ethyl 2-amino-4-thiazolyl acetate from thick (2-amino-5-methyl-phenyl)-cyclopropyl-ketone.

¹H?NMR(400MHz；CDCl ₃)：δ1.04-1.10(m，2H)，1.24-1.30(m，5H)，2.39(s，3H)，2.62-2.72(m，1H)，3.73(s，2H)，4.20(q，2H)，6.78(s，1H)，7.37(dd，1H)，7.89(d，1H)，8.37(d，1H)，9.42(brs，2H)，11.50(s，1H)；HPLC-MS：m/z＝410.0(M+23)；Rt＝4.11min.

Embodiment 467 (common processes J)

2-[3-(2-cyclopropane carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (111mg, 99%) is that (120mg is 0.31mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.04(brs，4H)，2.38(s，3H)，2.76(brs，1H)，3.58(s，2H)，6.86(s，1H)，6.92(d，1H)，8.02(s，1H)，8.14(d，1H)，10.46(s，1H)，12.05(brs，2H)；HPLC-MS：m/z＝382.0(M+23)；Rt＝3.38min.

Embodiment 468 (common processes AA)

2-[3-(2-tetramethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

According to the described similar mode of (2-amino-5-methyl-phenyl)-cyclopropyl-ketone, use cyclobutane-carboxylic acid methoxyl group-methyl-acid amides to replace cyclopropane-carboxylic acid methoxyl group-methyl-acid amides, thick (2-amino-5-methyl-phenyl)-cyclobutyl-ketone (80%, oil) of preparation.

Title compound (210mg, 49%) is that (200mg, 1.06mmol) (197mg 1.06mmol) is equipped with according to the common processes Dutch treatment with ethyl 2-amino-4-thiazolyl acetate from thick (2-amino-5-methyl-phenyl)-cyclobutyl-ketone.

¹H?NMR(400MHz；CDCl ₃)：δ1.30(t，3H)，1.83-2.50(m，6H)，2.36(s，3H)，3.76(s，2H)，4.05(p，1H)，4.22(q，2H)，6.80(s，1H)，7.35(d，1H)，7.52(s，1H)，8.41(brd，1H)，11.9(brs，1H)；HPLC-MS：m/z＝424.1(M+23)；Rt＝4.48min.

Embodiment 469 (common processes J)

2-[3-(2-tetramethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (112mg, 73%) is that (165mg is 0.41mmol) according to common processes J preparation from { 2-[3-(2-tetramethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.70-2.30(m，6H)，2.32(s，3H)，3.56(s，2H)，4.19(brt，1H)，6.86(s，1H)，7.39(d，1H)，7.63(s，1H)，8.22(d，1H)，10.81(s，1H)，12.15(brs，2H)；HPLC-MS：m/z＝396.1(M+23)；Rt＝3.75min.

Embodiment 470 (common processes AA)

2-[3-(2-hexanaphthene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

According to the described similar mode of (2-amino-5-methyl-phenyl)-cyclopropyl-ketone, use hexahydrobenzoic acid methoxyl group-methyl-acid amides to replace cyclopropane-carboxylic acid methoxyl group-methyl-acid amides, thick (2-amino-5-methyl-phenyl)-cyclohexyl-ketone (75%, oil) of preparation.

Title compound (188mg, 48%) is that (200mg, 0.92mmol) (171mg 1.06mmol) is equipped with according to the common processes Dutch treatment with ethyl 2-amino-4-thiazolyl acetate from thick (2-amino-5-methyl-phenyl)-cyclohexyl-ketone.

¹H?NMR(400MHz；CDCl ₃)：δ1.30(t，3H)，1.37-1.59(m，5H)，1.71-1.91(m，5H)，2.37(s，3H)，3.30(brs，1H)，3.73(s，2H)，4.22(q，2H)，6.78(s，1H)，7.34(d，1H)，7.68(s，1H)，8.39(brd，1H)，11.78(brs，1H)；HPLC-MS：m/z＝452.2(M+23)；Rt＝4.92min.

Embodiment 471 (common processes J)

2-[3-(2-hexanaphthene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (100mg, 89%) is that (112mg is 0.28mmol) according to common processes J preparation from { 2-[3-(2-hexanaphthene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.13-1.45(m，5H)，1.62-1.83(m，5H)，2.34(s，3H)，3.42(brs，1H)，3.57(s，2H)，6.83(s，1H)，7.39(d，1H)，7.81(s，1H)，8.15(d，1H)，10.50(s，1H)，12.07(brs，2H)；HPLC-MS：m/z＝402.0(M+1)；Rt＝4.18min.

Embodiment 472

2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-the acetic acid ethyl ester

Under the ice bath temperature, methylene dichloride (80mL) the solution adding ethyl oxalyl chloride (1.2mL) to ethyl thiazolamine-4-acetic ester (2g) stirs 1h with reactant.Reaction mixture is washed with water, concentrate organic phase, obtain N-(4-ethoxycarbonylmethyl group-thiazol-2-yl)-oxalyl amino acid ethyl ester (1.2g).

Add THF (5mL) and 2N lithium hydroxide (4mL) to N-(4-ethoxycarbonylmethyl group-thiazol-2-yl)-oxalyl amino acid ethyl ester (1g).The adularescent precipitation generates, and behind the 1h reaction mixture is acidified to pH5, and the filtered and recycled white precipitate is with mixture development in 1: 1 of ether and ethyl acetate, to remove unreacted raw material.Solid residue is dry in vacuum drying oven, obtain N-(4-ethoxycarbonylmethyl group-thiazol-2-yl)-oxalyl amino acid (300mg).

N-(4-ethoxycarbonylmethyl group-thiazol-2-yl)-oxalyl amino acid (80mg) is dissolved in DMF (5mL), adds (2-amino-5-methyl-phenyl)-cyclopentyl-ketone, succeeded by PyBOP.Reactant is stirred 24h, add water.Water, concentrates the organic phase drying with ether/ethyl acetate extraction, through purification by flash chromatography, obtains title compound (15mg).

¹H?NMR(CDCl ₃)：1.25(3H，t)，1.6-2.1(8H，m)，2.45(3H，s)，3.65-3.75(1H，m)，3.7(1H，s)，4.2(4H，q)，6.9(1H)，7.4(1H，dd)，7.8(1H，s)，8.65(1H，d)，10.5(1H，bs)，13.3(1H，s).

Embodiment 473

2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

To 2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-methyl alcohol (2mL) solution of acetic acid ethyl ester (15mg) adds 1N sodium hydroxide (1N), mixture at room temperature stirred 3h.Mixture with 1N HCl acidifying, is under reduced pressure concentrated, through the HPLC purifying, obtain title compound (4mg).

LCMS(m/z)：416(M+1)

¹H?NMR(CDCl ₃+MeOD)：1.6-2.1(8H，m)，2.45(3H，s)，3.7(1H，s)，3.70-3.85(1H，m)，6.9(1H)，7.4(1H，dd)，7.8(1H，s)，8.65(1H，d)，13.3(1H，s).

Embodiment 474

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-the acetic acid ethyl ester

To 5-chloro-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester (0.1g, 0.22mmol) DMF (4mL) solution add sodium bicarbonate (0.075g, 0.89mmol) and 2-pyridyl mercaptan (2-puridylthiole) (0.027g, 0.24mmol).In the pressure bottle of lucifuge, reaction mixture was stirred 2.0 hours under nitrogen at 80 ℃.Crude product obtains title compound (0.02g) through flash chromatography (Virahol/heptane 1: 4) and recrystallization (methylene dichloride/heptane) purifying.

¹H?NMR(300MHz，CDCl ₃)：δ1.20(t，3H)，1.60-1.82(m，4H)，1.82-2.02(m，4H)，2.38(s，3H)，3.68-3.80(m，1H)，3.85(s，2H)，4.12(q，2H)，7.00(t，2H)，7.35(d，1H)，7.50(t，1H)，7.73(s，1H)，8.40(m，2H)，11.80(s，1H).

Embodiment 475 (common processes (AA))

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

At-20 ℃, under nitrogen atmosphere, go through 10min to the Et of (4-trifluoromethyl-phenyl)-carboxylamine tertiary butyl ester (15mmol) that is stirring ₂O (40mL) solution drips the pentane solution (38mmol) of 1.7Mt-BuLi.Mixture is stirred 1.5h down at-15 ℃, go through 5min then and add Cyclopentane carboxylic acid methoxyl group-methyl-acid amides (20mmol).Make mixture be warmed to room temperature, stir other 1h, use moisture NH then ₄The Cl quencher.Separate organic phase, water CH ₂Cl ₂Extraction merges organic phase, and drying concentrates in a vacuum.Crude product is dissolved in CH ₂Cl ₂(25mL) and TFA (25mL), at room temperature stir 2h.Evaporation reaction mixture adds moisture NaHCO in a vacuum ₃To pH7, use CH ₂Cl ₂Extraction, drying concentrates, and obtains crude product, to its process purification by flash chromatography (Quad flash40, EtOAc-heptane 0: 1-＞1: 3).Obtain 70% (2-amino-5-trifluoromethyl-phenyl)-cyclopentyl-ketone, be oil.

Title compound (15%) is equipped with according to the common processes Dutch treatment from (2-amino-5-trifluoromethyl-phenyl)-cyclopentyl-ketone and ethyl 2-amino-4-thiazolyl acetate.

¹H?NMR(400MHz；CDCl ₃)：δ1.28(t，3H)，1.64-1.99(m，8H)，3.70(brt，1H)，3.74(s，2H)，4.20(q，2H)，6.74(s，1H)，7.73(d，1H)，8.13(s，1H)，8.74(brs，1H)，9.53(brs，1H)，11.82(brs，1H)；HPLC-MS：m/z＝492.1(M+23)；Rt＝5.02min.

Embodiment 476 (common processes J)

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (13mg, 33%) is that (42mg is 0.09mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.65-1.95(m，8H)，3.60(s，2H)，3.99(brs，1H)，6.94(s，1H)，7.90(d，1H)，8.25(brs，1H)，8.54(brs，1H)，10.94(brs，1H)，12.25(brs，2H)；HPLC-MS：m/z＝426.1(M+23)；Rt＝4.49min.

Embodiment 477 (common processes (AA))

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

At-20 ℃, under nitrogen atmosphere, go through 10min to the Et of (4-chloro-the phenyl)-carboxylamine tertiary butyl ester (35mmol) that is stirring ₂O (80mL) solution drips the pentane solution (88mmol) of 1.7M t-BuLi.Mixture is stirred 1.5h down at 0 ℃, go through 5min then and add Cyclopentane carboxylic acid methoxyl group-methyl-acid amides (45mmol).Make mixture be warmed to room temperature, stir other 1h, use moisture NH then ₄The Cl quencher.Separate organic phase, water CH ₂Cl ₂Extraction merges organic phase, and drying concentrates in a vacuum.Crude product is dissolved in CH ₂Cl ₂(50mL) and TFA (50mL), at room temperature stir 1h.Evaporation reaction mixture adds moisture NaHCO in a vacuum ₃To pH7, use CH ₂Cl ₂Extraction, drying concentrates, and obtains crude product, through purification by flash chromatography (Quad flash 65, EtOAc-heptane 0: 1-＞1: 3).Obtain 75% (2-amino-5-chloro-phenyl)-cyclopentyl-ketone, be oil.

Title compound (30%) is equipped with according to the common processes Dutch treatment from (2-amino-5-chloro-phenyl)-cyclopentyl-ketone and ethyl 2-amino-4-thiazolyl acetate.

¹H?NMR(400MHz；CDCl ₃)：δ1.28(t，3H)，1.62-1.99(m，8H)，3.3.67(brt，1H)，3.73(s，2H)，4.20(q，2H)，6.72(s，1H)，7.46(dd，1H)，7.84(d，1H)，8.56(brs，1H)，9.50(brs，1H)，11.58(brs，1H)；HPLC-MS：m/z＝458.0(M+23)；Rt＝4.86min.

Embodiment 478 (common processes J)

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (39mg, 85%) is that (49mg is 0.11mmol) according to common processes J preparation from { 2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.67-1.92(m，8H)，3.59(s，2H)，3.89(brs，1H)，6.88(s，1H)，7.63(d，1H)，8.04(brs，1H)，8.32(brs，1H)，10.64(s，1H)，12.20(brs，2H)；HPLC-MS：m/z＝430.0(M+23)；Rt＝4.11min.

Embodiment 479 (common processes (AA))

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-yl }-the acetic acid ethyl ester

At-30 ℃, under nitrogen atmosphere, go through 10min to the Et of (4-fluoro-the phenyl)-carboxylamine tertiary butyl ester (9.5mmol) that is stirring ₂O (20mL) solution drips the pentane solution (22mmol) of 1.7M t-BuLi.Mixture is stirred 1.5h down at-20 ℃, go through 5min then and add Cyclopentane carboxylic acid methoxyl group-methyl-acid amides (10.5mmol).Make mixture be warmed to room temperature, stir other 1h, use moisture NH then ₄The Cl quencher.Separate organic phase, water CH ₂Cl ₂Extraction merges organic phase, and drying concentrates in a vacuum.Crude product is dissolved in CH ₂Cl ₂(25mL) and TFA (25mL), at room temperature stir 2h.Evaporation reaction mixture adds moisture NaHCO in a vacuum ₃To pH7, use CH ₂Cl ₂Extraction, drying concentrates, and obtains crude product, to its process purification by flash chromatography (Quad flash 40, EtOAc-heptane 0: 1-＞1: 3).Obtain 60% (2-amino-5-fluoro-phenyl)-cyclopentyl-ketone, be oil.

Title compound (26%) is equipped with according to the common processes Dutch treatment from (2-amino-5-fluoro-phenyl)-cyclopentyl-ketone and ethyl 2-amino-4-thiazolyl acetate.

¹H?NMR(400MHz；CDCl ₃)：δ1.28(t，3H)，1.63-1.97(m，8H)，3.64(brt，1H)，3.73(s，2H)，4.20(q，2H)，6.72(s，1H)，7.22-7.29(m，1H)，7.58(dd，1H)，8.55(brs，1H)，9.40(brs，1H)，11.45(brs，1H)；HPLC-MS：m/z＝442.0(M+23)；Rt＝4.49min.

Embodiment 480 (common processes J)

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

Title compound (75mg, 87%) is that (92mg is 0.22mmol) according to common processes J preparation from { 2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-yl }-acetic acid ethyl ester.

¹H?NMR(400MHz；DMSO?d ₆)：δ1.65-1.94(m，8H)，3.57(s，2H)，3.84(brs，1H)，6.88(s，1H)，7.45(t，1H)，7.85(brs，1H)，8.25(brs，1H)，10.48(s，1H)，12.10(brs，2H)；HPLC-MS：m/z＝414.1(M+23)；Rt＝3.74min.

Utilize method disclosed herein, also can prepare following compounds:

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-phenyl)-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-(5-chloro-thiazol-2-yl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea

1-(5-chloro-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea

1-(5-chloro-thiazol-2-yl)-3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea

1-(5-chloro-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea

1-(5-bromo-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea

1-(5-bromo-thiazol-2-yl)-3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea

1-(5-bromo-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-(5-methylthio group-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-1-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

5-chloro-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-thiazole-4-carboxylic acid

5-chloro-2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-thiazole-4-carboxylic acid

5-bromo-2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-methylthio group-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-methylsulfonyl-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-carboxylic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-thiazole-4-yl }-acetic acid

5-chloro-2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-yl]-acetic acid

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-phenyl)-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea

1-(5-chloro-4-thiophenyl methyl-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea

1-(5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea

1-(1-5-bromo-4-thiophenyl methyl-thiazol-2-yl)-3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-(5-methylthio group-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-(5-methylsulfonyl-4-thiophenyl methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl] urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[4-thiophenyl methyl-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[4-thiophenyl methyl-5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1H-imidazoles-2-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1H-imidazoles-2-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-4-thiophenyl methyl-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-chloro-2-pentamethylene carbonyl-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridin-4-yl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-pentamethylene carbonyl-pyridin-3-yl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

1-(3-pentamethylene carbonyl-pyridine-2-yl)-3-[4-thiophenyl methyl-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazol-2-yl]-urea

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-chloro-2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-azoles-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{5-bromo-2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-methylthio group-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-{2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-methylsulfonyl-thiazole-4-ylmethyl }-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(pyridine-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(pyridine-2-sulfuryl base)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1 H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups] 5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-imidazoles-2-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-chloro-2-pentamethylene carbonyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-trifluoromethyl-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-dimethylamino-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridin-4-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(4-pentamethylene carbonyl-pyridin-3-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-[2-[3-(3-pentamethylene carbonyl-pyridine-2-yl)-urea groups]-5-(1H-tetrazolium-5-alkylsulfonyl)-thiazole-4-ylmethyl]-Toluidrin

N-(2-pentamethylene carbonyl-phenyl)-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-phenyl)-oxamide

N-(5-chloro-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-phenyl)-oxamide

4; N-(2-pentamethylene carbonyl-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-oxamide

5-bromo-2-[(2-pentamethylene carbonyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-chloro-2-[(2-pentamethylene carbonyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

2-[(2-pentamethylene carbonyl-phenyl amino oxalyl group)-amino]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[(2-pentamethylene carbonyl-phenyl amino oxalyl group)-amino]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[(2-pentamethylene carbonyl-phenyl amino oxalyl group)-amino]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[(2-pentamethylene carbonyl-phenyl amino oxalyl group)-amino]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(2-pentamethylene carbonyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-phenyl)-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-phenyl)-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-phenyl)-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-phenyl)-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-phenyl)-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-Malonamide

2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-bromo-2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-chloro-2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[2-(2-pentamethylene carbonyl-phenylamino formyl radical)-kharophen]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(2-pentamethylene carbonyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-phenyl)-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-phenyl)-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-isobutoxy-phenyl)-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-(2-isobutoxy-phenyl)-oxamide

N-(5-chloro-thiazol-2-yl)-N '-(2-isobutoxy-phenyl)-oxamide

N-(2-isobutoxy-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-(2-isobutoxy-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-oxamide

N-(2-isobutoxy-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-oxamide

2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-bromo-2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-chloro-2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

5-(1H-imidazoles-2-base sulfenyl)-2-[(2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

N-(2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-oxamide

N-(2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-(2-isobutoxy-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[5-(1 H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-oxamide

N-(2-isobutoxy-phenyl)-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-(2-isobutoxy-phenyl)-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-(2-isobutoxy-phenyl)-Malonamide

N-(2-isobutoxy-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-(2-isobutoxy-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-Malonamide

N-(2-isobutoxy-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-Malonamide

2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-bromo-2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-chloro-2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

5-(1H-imidazoles-2-base sulfenyl)-2-[2-(2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

N-(2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-Malonamide

N-(2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-Malonamide

N-(2-isobutoxy-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-phenyl)-Malonamide

N-[2-(2-methoxyl group-phenoxy group)-phenyl]-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-(5-chloro-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[2-(2-methoxyl group-phenoxy group)-phenyl]-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-(5-methylsulfonyl-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

(2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

(5-bromo-2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

(5-chloro-2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

(2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-5-methylthio group-thiazole-4-yl)-acetic acid

(5-methylsulfonyl-2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

[2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

(5-(1H-imidazoles-2-base sulfenyl)-2-{[2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

N-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[2-(2-methoxyl group-phenoxy group)-phenyl]-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[2-(2-methoxyl group-phenoxy group)-phenyl]-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-(5-methylsulfonyl-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

(2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

(5-bromo-2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

(5-chloro-2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

(2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-5-methylthio group-thiazole-4-yl)-acetic acid

(5-methylsulfonyl-2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

[2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

(5-(1H-imidazoles-2-base sulfenyl)-2-{2-[2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

N[4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-oxamide

N-(5-chloro-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-(1 H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-oxamide

2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-bromo-2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-chloro-2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[(2-pentamethylene carbonyl-4-methyl-phenyl amino oxalyl group)-amino]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-Malonamide

2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-bromo-2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-chloro-2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[2-(2-pentamethylene carbonyl-4-methyl-phenylamino formyl radical)-kharophen]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-4-methyl-phenyl)-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-4-methyl-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-(2-isobutoxy-4-methyl-phenyl)-oxamide

N-(5-chloro-thiazol-2-yl)-N '-(2-isobutoxy-4-methyl-phenyl)-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-oxamide

2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-bromo-2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-chloro-2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

5-(1H-imidazoles-2-base sulfenyl)-2-[(2-isobutoxy-4-methyl-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

N-(2-isobutoxy-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-oxamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-(2-isobutoxy-4-methyl-phenyl)-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-(2-isobutoxy-4-methyl-phenyl)-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-Malonamide

2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-bromo-2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-chloro-2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

5-(1H-imidazoles-2-base sulfenyl)-2-[2-(2-isobutoxy-4-methyl-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

N-(2-isobutoxy-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-isobutoxy-4-methyl-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[5-(1 H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-isobutoxy-4-methyl-phenyl)-Malonamide

N-[2-(2-methoxyl group-phenoxy group)-4-methyl-phenyl]-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-4-methyl-phenyl]-oxamide

N-(5-chloro-thiazol-2-yl)-N '-[2-(2-methoxyl group-phenoxy group)-4-methyl-phenyl]-oxamide

N-[N-(5 - methanesulfonyl- - thiazole -N-[N-[5 - (1H- imidazol - ( ( 5 - bromo - ( 5 - chloro - ( ( 5 - methylsulfonyl - [ ( 5 - (1H- imidazol -N-[4 - ( methyl -sulfonyl group - methyl ) - thiazol -N-[5 - bromo-4 - (methylsulfonyl group - methyl ) - thiazol -N-[5 - chloro - 4 - ( methyl -sulfonyl group - methyl ) - thiazol -N-[4 - ( methyl -sulfonyl group - methyl) -5 - (methylthio) - thiazol -N-[5 - methanesulfonyl -4 - ( methyl sulfonylamino - methyl ) - thiazol -N-[4 - ( methyl -sulfonyl group - methyl) -5 - ( pyridine -N-[5 - (1H- imidazol -N-[N-(5 - bromo - thiazol -N-(5 - chloro - thiazol -N-[N-(5 - methanesulfonyl- - thiazole -N-[N-[5 - (1H- imidazol - ( ( 5 - bromo - ( 5 - chloro - ( ( 5 - methylsulfonyl - [(5 - (1H- imidazol -N-[4 - ( methyl -sulfonyl group - methyl ) - thiazol -N-[5 - bromo-4 - (methylsulfonyl group - methyl ) - thiazol -N-[5 - chloro-4 - (methylsulfonyl group - methyl ) - thiazol -N-[4 - ( methyl -sulfonyl group - methyl) -5 - (methylthio) - thiazol -N- [ 5 - methanesulfonyl -4 - (methylsulfonyl group - methyl ) - thiazol -N-[4 - ( methyl -sulfonyl group - methyl) -5 - ( pyridine -N-[5 - (1H- imidazol- -N-(N-(5 - bromo - thiazol -N-(5 - chloro - thiazol -N-(N-(N-(N-({{5 - bromo - {5 - chloro - {{[[N - (N-[5 - bromo-4 - (methylsulfonyl group - methyl ) - thiazol -N-[5 - chloro-4 - (methylsulfonyl group - methyl ) - thiazol -N-(N-( N-(N-(N-(N-(5 - bromo - thiazol -N-(5 - chloro - thiazol -N-(N-(N-(N-({{5 - bromo - {5 - chloro - {{[[N-(N-[5 - bromo-4 - (methylsulfonyl group - methyl ) - thiazol -N-[5 - chloro-4 - (methylsulfonyl group - methyl ) - thiazole -N - (N-(N-(N-(N-(4 - fluoro -N-(5 - bromo - thiazol -N-(5 - chloro - thiazol -N-(4 - fluoro -N-(4 - fluoro - 2 - isobutoxy - phenyl )-N'-(5 - methylsulfonyl - thiazol-2 - yl ) - oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-oxamide

2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-bromo-2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-chloro-2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[(4-fluoro-2-isobutoxy-phenyl amino oxalyl group)-amino]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(4-fluoro-2-isobutoxy-phenyl)-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(4-fluoro-2-isobutoxy-phenyl)-oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-(4-fluoro-2-isobutoxy-phenyl)-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-(4-fluoro-2-isobutoxy-phenyl)-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-Malonamide

2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-bromo-2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

5-chloro-2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-thiazole-4-yl }-acetic acid

2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[2-(4-fluoro-2-isobutoxy-phenylamino formyl radical)-kharophen]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(4-fluoro-2-isobutoxy-phenyl)-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(4-fluoro-2-isobutoxy-phenyl)-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-(4-fluoro-2-isobutoxy-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-(5-chloro-thiazol-2-yl)-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-(5-methylsulfonyl-thiazol-2-yl)-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-oxamide

(2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

(5-bromo-2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

(5-chloro-2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-thiazole-4-yl)-acetic acid

(2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-5-methylthio group-thiazole-4-yl)-acetic acid

(2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-5-methylsulfonyl-thiazole-4-yl)-acetic acid

[2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-{[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl amino oxalyl group]-amino }-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-thiazol-2-yl-Malonamide

N-(5-bromo-thiazol-2-yl)-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-(5-chloro-thiazol-2-yl)-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-(5-methylthio group-thiazol-2-yl)-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-(5-methylsulfonyl-thiazol-2-yl)-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-Malonamide

(2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

(5-bromo-2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

(5-chloro-2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-thiazole-4-yl)-acetic acid

(2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-5-methylthio group-thiazole-4-yl)-acetic acid

(2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-5-methylsulfonyl-thiazole-4-yl)-acetic acid

[2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-{2-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenylamino formyl radical]-kharophen }-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[4-(methanesulfonamido-methyl)-5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-Malonamide

N-[4-fluoro-2-(2-methoxyl group-phenoxy group)-phenyl]-N '-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-Malonamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-thiazol-2-yl-oxamide

N-(5-bromo-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-oxamide

N-(5-chloro-thiazol-2-yl)-N '-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-(5-methylthio group-thiazol-2-yl)-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-(5-methylsulfonyl-thiazol-2-yl)-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-oxamide

2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-bromo-2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

5-chloro-2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-thiazole-4-yl }-acetic acid

2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-5-methylthio group-thiazole-4-yl }-acetic acid

2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-5-methylsulfonyl-thiazole-4-yl }-acetic acid

[2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-5-(pyridine-2-base sulfenyl)-thiazole-4-yl]-acetic acid

[2-[(2-pentamethylene carbonyl-4-methoxyl group-phenyl amino oxalyl group)-amino]-5-(1H-imidazoles-2-base sulfenyl)-thiazole-4-yl]-acetic acid

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-[4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-[5-bromo-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-oxamide

N-[5-chloro-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-[4-(methanesulfonamido-methyl)-5-methylthio group-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-[5-methylsulfonyl-4-(methanesulfonamido-methyl)-thiazol-2-yl]-oxamide

N-(2-pentamethylene carbonyl-4-methoxyl group-phenyl)-N '-[N-(2-pentamethylene carbonyl-N-(N-[N-[4-(methanesulfonamido-methyl)-N-[N-[4-(methanesulfonamido-methyl)-N-[5-(1H-imidazoles-2-base sulfenyl)-4-(methanesulfonamido-methyl)-thiazol-2-yl]-N '-[4-methoxyl group-2-(2-methoxyl group-phenoxy group)-phenyl]-Malonamide

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-morpholine-4-ylmethyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-dimethylamino methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

1-[5-(4-ethanoyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-piperazine-1-yl)-acetic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-1H-imidazoles-4-carboxylic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl methyl)-thiazol-2-yl]-urea

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-tetrazolium-1-yl)-acetic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-base sulfenyl methyl]-thiazol-2-yl }-urea

(5-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-tetrazolium-1-yl)-acetic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-alkylsulfonyl methyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(1H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-sulfuryl ylmethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridin-3-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-4-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridin-4-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridin-3-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-base oxygen ylmethyl)-thiazol-2-yl]-urea

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenyl)-acetic acid

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-phenyl)-acetic acid

(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenyl)-acetic acid

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenyl)-propionic acid

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-phenyl)-propionic acid

3-(4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenyl)-propionic acid

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-phenylformic acid

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenylformic acid

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenylformic acid

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-ethanamide

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-Toluidrin

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(pyridine-2-base aminomethyl)-thiazol-2-yl]-urea

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-_ azoles-4-carboxylic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carboxylic acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-the thiazole-5-carboxylic acid acid amides

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-the thiazole-5-carboxylic acid methyl nitrosourea

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-acetic acid

(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-methylsulfonyl-amino)-acetic acid

N-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-Toluidrin

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-acetic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethanamide

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-N-methyl-ethanamide

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-kharophen)-acetic acid

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethanoyl)-Toluidrin

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-Toluidrin

N-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-ethanamide

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-guanidine radicals methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-urea groups methyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-urea

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-the carboxylamine methyl ester

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the carboxylamine methyl ester

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-guanidine radicals-ethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-urea groups-ethyl)-thiazol-2-yl]-urea

[3-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-urea groups]-acetic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-{2-[3-(2-dimethylamino-ethyl)-urea groups]-ethyl }-thiazol-2-yl)-urea

(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-carboxylamine 2-dimethylamino-ethyl ester

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-urea

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-1H-imidazoles-4-carboxylic acid

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-nicotinic acid

6-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-nicotinic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

[4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-phenyl]-acetic acid

[4-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylsulfonyl)-phenyl]-acetic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(pyridine-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(pyridine-2-sulfuryl base)-ethyl]-thiazol-2-yl }-urea

6-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-nicotinic acid

6-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylsulfonyl)-nicotinic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(5-[1,2,4] _ diazole-5-ylmethyl-thiazol-2-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-[1,2,4] _ diazole-5-base-ethyl)-thiazol-2-yl]-urea

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-butyric acid

1-(2-isobutoxy-4-methyl-phenyl)-3-(5-piperidines-1-ylmethyl-thiazol-2-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(5-morpholine-4-ylmethyl-thiazol-2-yl)-urea

1-(5-dimethylamino methyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(5-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(4-methyl-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

1-[5-(4-ethanoyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-piperazine-1-yl)-acetic acid

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-1H-imidazoles-4-carboxylic acid

1-[5-(1H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl methyl)-thiazol-2-yl]-urea

(5-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-tetrazolium-1-yl)-acetic acid

1-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-base sulfenyl methyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

(5-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-tetrazolium-1-yl)-acetic acid

1-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-alkylsulfonyl methyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[5-(1H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-sulfuryl ylmethyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-3-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-4-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-4-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-3-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-base oxygen ylmethyl)-thiazol-2-yl]-urea

(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenyl)-acetic acid

(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-phenyl)-acetic acid

(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenyl)-acetic acid

3-(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenyl)-propionic acid

3-(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-phenyl)-propionic acid

3-(4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenyl)-propionic acid

4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-phenylformic acid

4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenylformic acid

4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenylformic acid

N-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-ethanamide

N-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-Toluidrin

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-base aminomethyl)-thiazol-2-yl]-urea

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-_ azoles-4-carboxylic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carboxylic acid

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-the thiazole-5-carboxylic acid acid amides

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-the thiazole-5-carboxylic acid methyl nitrosourea

(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-acetic acid

(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-methylsulfonyl-amino)-acetic acid

N-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-Toluidrin

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-acetic acid

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethanamide

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-N-methyl-ethanamide

(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-kharophen)-acetic acid

N-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethanoyl)-Toluidrin

N-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-Toluidrin

N-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-ethanamide

1-(5-guanidine radicals methyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(5-urea groups methyl-thiazol-2-yl)-urea

1-{5-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-the carboxylamine methyl ester

(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the carboxylamine methyl ester

1-[5-(2-guanidine radicals-ethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(2-urea groups-ethyl)-thiazol-2-yl]-urea

[3-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-urea groups]-acetic acid

1-(5-{2-[3-(2-dimethylamino-ethyl)-urea groups]-ethyl }-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-carboxylamine 2-dimethylamino-ethyl ester

1-{5-[2-(1H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-{5-[2-(1H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-urea

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-1H-imidazoles-4-carboxylic acid

6-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazol-5-methylthiol }-nicotinic acid

6-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-nicotinic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

[4-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-phenyl]-acetic acid

[4-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylsulfonyl)-phenyl]-acetic acid

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(pyridine-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(pyridine-2-sulfuryl base)-ethyl]-thiazol-2-yl }-urea

6-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-nicotinic acid

6-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethylsulfonyl)-nicotinic acid

1-(2-isobutoxy-4-methyl-phenyl)-3-(5-[1,2,4] _ diazole-5-ylmethyl-thiazol-2-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(2-[1,2,4] _ diazole-5-base-ethyl)-thiazol-2-yl]-urea

4-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-butyric acid

1-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-1H-imidazoles-4-carboxylic acid

1-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-3-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-4-alkylsulfonyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-4-yl sulfenyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridin-3-yl sulfenyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

6-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid

6-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-nicotinic acid

1-(2-isobutoxy-4-methyl-phenyl)-3-(5-methylsulfonyl-thiazol-2-yl)-urea

3-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-propionic acid

3-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid

1-(5-bromo-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

5-chloro-2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(5-piperidines-1-ylmethyl-thiazol-2-yl)-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(5-morpholine-4-ylmethyl-thiazol-2-yl)-urea

1-(5-dimethylamino methyl-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(5-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(4-methyl-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

1-[5-(4-ethanoyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[5-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-piperazine-1-yl]-acetic acid

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazol-5-methylthiol)-1H-imidazoles-4-carboxylic acid

1-[5-(1H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(4-methyl-4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl methyl)-thiazol-2-yl]-urea

[5-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazol-5-methylthiol)-tetrazolium-1-yl]-acetic acid

1-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-base sulfenyl methyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

[5-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base methylsulfonyl)-tetrazolium-1-yl]-acetic acid

1-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-alkylsulfonyl methyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(4-methyl-4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[5-(1H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-sulfuryl ylmethyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-3-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-4-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-4-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-3-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-base oxygen ylmethyl)-thiazol-2-yl]-urea

[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethoxy)-phenyl]-acetic acid

[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazol-5-methylthiol)-phenyl]-acetic acid

[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base methylsulfonyl)-phenyl]-acetic acid

3-[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethoxy)-phenyl]-propionic acid

3-[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazol-5-methylthiol)-phenyl]-propionic acid

3-[4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base methylsulfonyl)-phenyl]-propionic acid

4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazol-5-methylthiol)-phenylformic acid

4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base methylsulfonyl)-phenylformic acid

4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethoxy)-phenylformic acid

N-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-ethanamide

N-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-Toluidrin

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-base aminomethyl)-thiazol-2-yl]-urea

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base methylsulfonyl)-1H-imidazoles-4-carboxylic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-1H-imidazoles-4-carboxylic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-_ azoles-4-carboxylic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carboxylic acid

2-[3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-the thiazole-5-carboxylic acid acid amides

2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-the thiazole-5-carboxylic acid methyl nitrosourea

[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-acetic acid

[methylsulfonyl-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-acetic acid

N-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-Toluidrin

(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-acetic acid

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethanamide

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-N-methyl-ethanamide

[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-kharophen]-acetic acid

N-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethanoyl]-Toluidrin

N-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-Toluidrin

N-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-ethanamide

1-(5-guanidine radicals methyl-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(5-urea groups methyl-thiazol-2-yl)-urea

1-{5-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-carboxylamine 2-dimethylamino-ethyl ester

(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-the carboxylamine methyl ester

[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-the carboxylamine methyl ester

1-[5-(2-guanidine radicals-ethyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(2-urea groups-ethyl)-thiazol-2-yl]-urea

3-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-urea groups }-acetic acid

1-(5-{2-[3-(2-dimethylamino-ethyl)-urea groups]-ethyl }-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-carboxylamine 2-dimethylamino-ethyl ester

1-{5-[2-(1H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-{5-[2-(1H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-urea

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethylmercapto group]-1H-imidazoles-4-carboxylic acid

6-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazol-5-methylthiol)-nicotinic acid

6-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base methylsulfonyl)-nicotinic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethylmercapto group]-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

4-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethylmercapto group]-phenyl }-acetic acid

4-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethylsulfonyl]-phenyl }-acetic acid

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(pyridine-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(pyridine-2-sulfuryl base)-ethyl]-thiazol-2-yl }-urea

6-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethylmercapto group]-nicotinic acid

6-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethylsulfonyl]-nicotinic acid

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(5-[1,2,4] _ diazole-5-ylmethyl-thiazol-2-yl)-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(2-[1,2,4] _ diazole-5-base-ethyl)-thiazol-2-yl]-urea

4-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-butyric acid

1-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-urea

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base sulfenyl)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-alkylsulfonyl)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-alkylsulfonyl)-1H-imidazoles-4-carboxylic acid

1-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-3-alkylsulfonyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-4-alkylsulfonyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-4-yl sulfenyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridin-3-yl sulfenyl)-thiazol-2-yl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

6-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base sulfenyl)-nicotinic acid

6-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-alkylsulfonyl)-nicotinic acid

1-(5-methylsulfonyl-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

3-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-alkylsulfonyl)-propionic acid

3-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-base sulfenyl)-propionic acid

1-(5-bromo-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

(5-chloro-2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid

(5-bromo-2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-acetic acid

1-(5-chloro-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-(5-chloro-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(5-piperidines-1-ylmethyl-thiazol-2-yl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(5-morpholine-4-ylmethyl-thiazol-2-yl)-urea

1-(5-dimethylamino methyl-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(5-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-[5-(4-methyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-[5-(4-ethanoyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-[5-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-piperazine-1-yl)-acetic acid

2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazol-5-methylthiol }-1H-imidazoles-4-carboxylic acid

1-[5-(1H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl methyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(4H-[1,2,4] triazole-3-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-base sulfenyl methyl)-thiazol-2-yl]-urea

(5-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazol-5-methylthiol }-tetrazolium-1-yl)-acetic acid

1-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-base sulfenyl methyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

(5-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-tetrazolium-1-yl)-acetic acid

1-{5-[1-(2-dimethylamino-ethyl)-1H-tetrazolium-5-alkylsulfonyl methyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(1-methyl isophthalic acid H-tetrazolium-5-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(4-methyl-4H-[1,2,4] triazole-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-[5-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-[5-(1H-imidazoles-2-alkylsulfonyl methyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-2-sulfuryl ylmethyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-2-base sulfenyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridin-3-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-3-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridin-4-yl sulfenyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-4-alkylsulfonyl methyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridin-4-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridin-3-yl oxygen ylmethyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-2-base oxygen ylmethyl)-thiazol-2-yl]-urea

(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenyl)-acetic acid

(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazol-5-methylthiol }-phenyl)-acetic acid

(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenyl)-acetic acid

3-(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenyl)-propionic acid

3-(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazol-5-methylthiol }-phenyl)-propionic acid

3-(4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenyl)-propionic acid

4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazol-5-methylthiol }-phenylformic acid

4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-phenylformic acid

4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethoxy }-phenylformic acid

N-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-ethanamide

N-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-Toluidrin

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-2-base aminomethyl)-thiazol-2-yl]-urea

2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-_ azoles-4-carboxylic acid

1-methyl-2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1H-imidazoles-4-carboxylic acid

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carboxylic acid

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-the thiazole-5-carboxylic acid acid amides

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-the thiazole-5-carboxylic acid methyl nitrosourea

(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-acetic acid

(methylsulfonyl-2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-acetic acid

N-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-Toluidrin

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-acetic acid

2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethanamide

N-methyl-2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethanamide

(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-kharophen)-acetic acid

N-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethanoyl)-Toluidrin

N-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-Toluidrin

N-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-ethanamide

1-(5-guanidine radicals methyl-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(5-urea groups methyl-thiazol-2-yl)-urea

1-{5-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-the carboxylamine methyl ester

(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the carboxylamine methyl ester

1-[5-(2-guanidine radicals-ethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(2-urea groups-ethyl)-thiazol-2-yl]-urea

[3-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-urea groups]-acetic acid

1-(5-{2-[3-(2-dimethylamino-ethyl)-urea groups]-ethyl }-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-carboxylamine 2-dimethylamino-ethyl ester

1-{5-[2-(1H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-{5-[2-(1H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-ethyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-1-{5-[2-(1-methyl isophthalic acid H-imidazoles-2-alkylsulfonyl)-ethyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-1H-imidazoles-4-carboxylic acid

6-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazol-5-methylthiol }-nicotinic acid

6-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base methylsulfonyl }-nicotinic acid

1-methyl-2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-1H-imidazoles-4-carboxylic acid

[4-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-phenyl]-acetic acid

[4-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethylsulfonyl)-phenyl]-acetic acid

1-(4-methyl-2-piperidines-1-base-phenyl)-3-{5-[2-(pyridine-2-base sulfenyl)-ethyl]-thiazol-2-yl }-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-{5-[2-(pyridine-2-sulfuryl base)-ethyl]-thiazol-2-yl }-urea

6-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethylmercapto group)-nicotinic acid

6-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethylsulfonyl)-nicotinic acid

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(5-[1,2,4] _ diazole-5-ylmethyl-thiazol-2-yl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(2-[1,2,4] _ diazole-5-base-ethyl)-thiazol-2-yl]-urea

4-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-butyric acid

1-[5-(1H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-[5-(1-methyl isophthalic acid H-imidazoles-2-base sulfenyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-methyl-2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base sulfenyl }-1H-imidazoles-4-carboxylic acid

1-methyl-2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-1H-imidazoles-4-carboxylic acid

1-[5-(1H-imidazoles-2-alkylsulfonyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-2-sulfuryl base)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-3-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-4-alkylsulfonyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridin-4-yl sulfenyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridin-3-yl sulfenyl)-thiazol-2-yl]-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(pyridine-2-base sulfenyl)-thiazol-2-yl]-urea

6-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base sulfenyl }-nicotinic acid

6-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-nicotinic acid

1-(5-methylsulfonyl-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

3-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-alkylsulfonyl }-propionic acid

3-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-base sulfenyl }-propionic acid

1-(5-bromo-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

5-chloro-2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

5-bromo-2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-yl }-acetic acid

N-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-yl }-ethanoyl)-Toluidrin

1-(4-dimethylamino methyl-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(4-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-[4-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(4-morpholine-4-ylmethyl-thiazol-2-yl)-urea

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-carboxylic acid's methyl nitrosourea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-ylmethyl }-the carboxylamine methyl ester

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(4-urea groups methyl-thiazol-2-yl)-urea

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester

1-(4-guanidine radicals methyl-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

(3-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-4-ylmethyl }-urea groups)-acetic acid

1-{4-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

N-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-Toluidrin

N-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-ethanoyl)-Toluidrin

1-(4-dimethylamino methyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(4-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[4-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(4-morpholine-4-ylmethyl-thiazol-2-yl)-urea

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-carboxylic acid's methyl nitrosourea

1-(2-isobutoxy-4-methyl-phenyl)-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-the carboxylamine methyl ester

1-(2-isobutoxy-4-methyl-phenyl)-3-(4-urea groups methyl-thiazol-2-yl)-urea

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-carboxylamine 2-dimethylamino-ethyl ester

1-(4-guanidine radicals methyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

(3-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-4-ylmethyl }-urea groups)-acetic acid

1-{4-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

N-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-ylmethyl)-Toluidrin

N-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-yl)-ethanoyl]-Toluidrin

1-(4-dimethylamino methyl-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(4-piperazine-1-ylmethyl-thiazol-2-yl)-urea

1-[4-(4-methylsulfonyl-piperazine-1-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(4-morpholine-4-ylmethyl-thiazol-2-yl)-urea

2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-carboxylic acid's methyl nitrosourea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[4-(morpholine-4-carbonyl)-thiazol-2-yl]-urea

(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-ylmethyl)-the carboxylamine methyl ester

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(4-urea groups methyl-thiazol-2-yl)-urea

(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-ylmethyl)-carboxylamine 2-dimethylamino-ethyl ester

1-(4-guanidine radicals methyl-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

[3-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-4-ylmethyl)-urea groups]-acetic acid

1-{4-[3-(2-dimethylamino-ethyl)-urea groups methyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-_ azoles-4-carboxylic acid

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-_ azoles-4-carboxylic acid

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-]-methyl isophthalic acid H-imidazoles-4-carboxylic acid

6-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-nicotinic acid

2-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-pyrimidine-5-carboxylic acid

5-(2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1-methyl isophthalic acid H-pyrazoles-3-carboxylic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-5-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-5-Trifluoromethyl-1 H-imidazoles-4-carboxylic acid

1-{5-[2-(the 1H-benzimidazolyl-2 radicals-yl)-ethyl]-thiazol-2-yl }-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1 H-imidazo [4,5-#b! ] pyridine-2-yl)-ethyl]-thiazol-2-yl }-urea

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-_ azoles-4-carboxylic acid

1-[5-(1H-benzimidazolyl-2 radicals-ylmethyl)-thiazol-2-yl]-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(the 1H-imidazo [4,5-#b! ] pyridine-2-ylmethyl)-thiazol-2-yl]-urea

1-(5-benzo _ azoles-2-ylmethyl-thiazol-2-yl)-3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(the 5-_ azoles also [4,5-#b! ] pyridine-2-ylmethyl-thiazol-2-yl)-urea

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the 5-trifluoromethyl-_ azoles-4-carboxylic acid

2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the 5-methyl-_ azoles-4-carboxylic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(4-methyl-4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

[3-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-[1,2,4] triazole-4-yl]-acetic acid

[5-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-tetrazolium-1-yl]-acetic acid

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-{5-[2-(1H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-(2-[1,3,4] thiadiazoles-2-base-ethyl)-thiazol-2-yl]-urea

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-carboxylic acid [1,3,4] thiadiazoles-2-base acid amides

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[5-([1,3,4] thiadiazoles-2-base aminomethyl)-thiazol-2-yl]-urea

[2-(2-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-imidazoles-1-yl]-acetic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-1H-imidazoles-4-carboxylic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-_ azoles-4-carboxylic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-amino]-1H-imidazoles-4-carboxylic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-amino]-_ azoles-4-carboxylic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-amino]-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

6-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-nicotinic acid

2-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-pyrimidine-5-carboxylic acid

5-[(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carbonyl)-amino]-1-methyl isophthalic acid H-pyrazoles-3-carboxylic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-5-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-5-Trifluoromethyl-1 H-imidazoles-4-carboxylic acid

1-{5-[2-(the 1H-benzimidazolyl-2 radicals-yl)-ethyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-{5-[2-(the 1H-imidazo [4,5-#b! ] pyridine-2-yl)-ethyl]-thiazol-2-yl }-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-1H-imidazoles-4-carboxylic acid

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-ylmethyl)-_ azoles-4-carboxylic acid

1-[5-(1H-benzimidazolyl-2 radicals-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[5-(the 1H-imidazo [4,5-#b! ] pyridine-2-ylmethyl)-thiazol-2-yl]-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-(5-benzo _ azoles-2-ylmethyl-thiazol-2-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(the 5-_ azoles also [4,5-#b! ] pyridine-2-ylmethyl-thiazol-2-yl)-urea

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-the 5-trifluoromethyl-_ azoles-4-carboxylic acid

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-the 5-methyl-_ azoles-4-carboxylic acid

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(4-methyl-4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

3-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-[1,2,4] triazole-4-yl }-acetic acid

5-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-tetrazolium-1-yl }-acetic acid

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1-methyl isophthalic acid H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-{5-[2-(1H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-(2-[1,3,4] thiadiazoles-2-base-ethyl)-thiazol-2-yl]-urea

2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-carboxylic acid [1,3,4] thiadiazoles-2-base acid amides

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[5-([1,3,4] thiadiazoles-2-base aminomethyl)-thiazol-2-yl]-urea

2-[2-(2-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-thiazole-5-yl)-ethyl]-imidazoles-1-yl }-acetic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-_ azoles-4-carboxylic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-_ azoles-4-carboxylic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

6-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-nicotinic acid

2-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-pyrimidine-5-carboxylic acid

5-(2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1-methyl isophthalic acid H-pyrazoles-3-carboxylic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-5-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-5-Trifluoromethyl-1 H-imidazoles-4-carboxylic acid

1-{5-[2-(the 1H-benzimidazolyl-2 radicals-yl)-ethyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-{5-[2-(the 1H-imidazo [4,5-#b! ] pyridine-2-yl)-ethyl]-thiazol-2-yl }-3-(2-isobutoxy-4-methyl-phenyl)-urea

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-1-methyl isophthalic acid H-imidazoles-4-carboxylic acid

2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-ylmethyl }-_ azoles-4-carboxylic acid

1-[5-(1H-benzimidazolyl-2 radicals-ylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-[5-(the 1H-imidazo [4,5-#b! ] pyridine-2-ylmethyl)-thiazol-2-yl]-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(5-benzo _ azoles-2-ylmethyl-thiazol-2-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(the 5-_ azoles also [4,5-#b! ] pyridine-2-ylmethyl-thiazol-2-yl)-urea

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the 5-trifluoromethyl-_ azoles-4-carboxylic acid

2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the 5-methyl-_ azoles-4-carboxylic acid

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(4-methyl-4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

[3-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-[1,2,4] triazole-4-yl]-acetic acid

[5-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-tetrazolium-1-yl]-acetic acid

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-{5-[2-(1H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-(2-[1,3,4] thiadiazoles-2-base-ethyl)-thiazol-2-yl]-urea

2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-carboxylic acid [1,3,4] thiadiazoles-2-base acid amides

1-(2-isobutoxy-4-methyl-phenyl)-3-[5-([1,3,4] thiadiazoles-2-base aminomethyl)-thiazol-2-yl]-urea

[2-(2-{2-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-imidazoles-1-yl]-acetic acid

2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-_ azoles-4-carboxylic acid

1-methyl-2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-1H-imidazoles-4-carboxylic acid

2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-_ azoles-4-carboxylic acid

1-methyl-2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-amino)-1H-imidazoles-4-carboxylic acid

6-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-nicotinic acid

2-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-pyrimidine-5-carboxylic acid

1-methyl-5-(2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carbonyl }-amino)-1H-pyrazoles-3-carboxylic acid

5-methyl-2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-1H-imidazoles-4-carboxylic acid

2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-5-Trifluoromethyl-1 H-imidazoles-4-carboxylic acid

1-{5-[2-(the 1H-benzimidazolyl-2 radicals-yl)-ethyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-{5-[2-(the 1H-imidazo [4,5-#b! ] pyridine-2-yl)-ethyl]-thiazol-2-yl }-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-1H-imidazoles-4-carboxylic acid

1-methyl-2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-1H-imidazoles-4-carboxylic acid

2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-ylmethyl }-_ azoles-4-carboxylic acid

1-[5-(1H-benzimidazolyl-2 radicals-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-[5-(the 1H-imidazo [4,5-#b! ] pyridine-2-ylmethyl)-thiazol-2-yl]-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(5-benzo _ azoles-2-ylmethyl-thiazol-2-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(the 5-_ azoles also [4,5-#b! ] pyridine-2-ylmethyl-thiazol-2-yl)-urea

2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-the 5-trifluoromethyl-_ azoles-4-carboxylic acid

5-methyl-2-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-_ azoles-4-carboxylic acid

1-(4-methyl-2-piperidines-1-base-phenyl)-3-{5-[2-(4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-{5-[2-(4-methyl-4H-[1,2,4] triazole-3-yl)-ethyl]-thiazol-2-yl }-urea

[3-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-[1,2,4] triazole-4-yl]-acetic acid

[5-(2-{2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-yl }-ethyl)-tetrazolium-1-yl]-acetic acid

1-(4-methyl-2-piperidines-1-base-phenyl)-3-{5-[2-(1-methyl isophthalic acid H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-{5-[2-(1H-tetrazolium-5-yl)-ethyl]-thiazol-2-yl }-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-(2-[1,3,4] thiadiazoles-2-base-ethyl)-thiazol-2-yl]-urea

2-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-thiazole-5-carboxylic acid [1,3,4] thiadiazoles-2-base acid amides

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[5-([1,3,4] thiadiazoles-2-base aminomethyl)-thiazol-2-yl]-urea

1-(2-pentamethylene carbonyl-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-pentamethylene carbonyl-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-pentamethylene carbonyl-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-isobutoxy-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-isobutoxy-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-isobutoxy-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(2-isobutoxy-phenyl)-urea

1-(2-isobutoxy-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-[2-(2-methoxyl group-benzoyl)-phenyl]-3-[1,2,4] thiadiazoles-5-base-urea

(5-{3-[2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-yl)-acetic acid

N-(5-{3-[2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-ylmethyl)-Toluidrin

1-[2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-[2-(2-methoxyl group-benzoyl)-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-3-[2-(2-methoxyl group-benzoyl)-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-piperidines-1-base-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-3-(2-piperidines-1-base-phenyl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(2-piperidines-1-base-phenyl)-urea

1-(3-methyl-[1,2,4] thiadiazoles-5-yl)-3-(2-piperidines-1-base-phenyl)-urea

1-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-3-(2-piperidines-1-base-phenyl)-urea

1-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-3-(2-piperidines-1-base-phenyl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-methyl-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-isobutoxy-4-methyl-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-isobutoxy-4-methyl-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(2-isobutoxy-4-methyl-phenyl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-4-methyl-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-[1,2,4] thiadiazoles-5-base-urea

(5-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-yl)-acetic acid

N-(5-{3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-ylmethyl)-Toluidrin

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-3-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-methyl-phenyl]-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(4-methyl-2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-3-(4-methyl-2-piperidines-1-base-phenyl)-urea

1-(4-methyl-2-piperidines-1-base-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-pentamethylene carbonyl-4-fluoro-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-fluoro-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-fluoro-2-isobutoxy-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(4-fluoro-2-isobutoxy-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(4-fluoro-2-isobutoxy-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(4-fluoro-2-isobutoxy-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(4-fluoro-2-isobutoxy-phenyl)-urea

1-(4-fluoro-2-isobutoxy-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-fluoro-2-isobutoxy-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-fluoro-2-isobutoxy-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-[1,2,4] thiadiazoles-5-base-urea

(5-{3-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-yl)-acetic acid

N-(5-{3-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-ylmethyl)-Toluidrin

1-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-urea

1-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-[4-fluoro-2-(2-methoxyl group-benzoyl)-phenyl]-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-fluoro-2-piperidines-1-base-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(4-fluoro-2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(4-fluoro-2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(4-fluoro-2-piperidines-1-base-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(4-fluoro-2-piperidines-1-base-phenyl)-urea

1-(4-fluoro-2-piperidines-1-base-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-fluoro-2-piperidines-1-base-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-fluoro-2-piperidines-1-base-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-pentamethylene carbonyl-4-morpholine-4-base-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-4-morpholine-4-base-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(2-isobutoxy-4-morpholine-4-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(2-isobutoxy-4-morpholine-4-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(2-isobutoxy-4-morpholine-4-base-phenyl)-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(2-isobutoxy-4-morpholine-4-base-phenyl)-urea

1-(2-isobutoxy-4-morpholine-4-base-phenyl)-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-4-morpholine-4-base-phenyl)-3-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(2-isobutoxy-4-morpholine-4-base-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-3-[1,2,4] thiadiazoles-5-base-urea

(5-{3-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-yl)-acetic acid

N-(5-{3-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-urea groups }-[1,2,4] thiadiazoles-3-ylmethyl)-Toluidrin

1-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-3-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-3-(3-methyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-3-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-urea

1-[2-(2-methoxyl group-benzoyl)-4-morpholine-4-base-phenyl]-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

1-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-3-[1,2,4] thiadiazoles-5-base-urea

5-[3-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-yl }-acetic acid

N-{5-[3-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-urea groups]-[1,2,4] thiadiazoles-3-ylmethyl }-Toluidrin

1-(3-methoxyl group-[1,2,4] thiadiazoles-5-yl)-3-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-urea

1-(3-ethyl-[1,2,4] thiadiazoles-5-yl)-3-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-urea

1-(3-methyl-[1,2,4] thiadiazoles-5-yl)-3-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-urea

1-(3-sec.-propyl-[1,2,4] thiadiazoles-5-yl)-3-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-urea

1-(4-morpholine-4-base-2-piperidines-1-base-phenyl)-3-(3-phenyl-[1,2,4] thiadiazoles-5-yl)-urea

4-{2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl }-2-methyl-butyric acid

2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-4,5,6,7-tetrahydrochysene-benzothiazole-7-carboxylic acid

Biological assay

Glucokinase activation measurement (I)

The glucokinase activity be by with the phase coupling of glucose 6-phosphate dehydrogenase through spectrometric, to measure compound to the activation of glucokinase.Final mensuration thing contains 50mM Hepes, pH7.1,50mM KCl, 5mM MgCl ₂, 2mM dithiothreitol (DTT), 0.6mMNADP, 1mM ATP, 0.195 μ M G-6-P desaturase (Roche, 127671), 15nM recombinant human glucokinase.Glucokinase is people liver glucokinase, and the N-end is soluble protein by terminal His-tag ((His) 8-VEQILA......Q466) brachymemma of N-at expression in escherichia coli, and enzymic activity is equivalent to from the GK of liver extraction.

The purifying of people's glucokinase (hGK) of His-mark is following carrying out: will be suspended in 5mL from the cell granulations of 50mL culture of Escherichia coli again and extract (25mM HEPES, pH8.0,1mM MgCl in the buffer A ₂, 150mM NaCl, 2mM mercaptoethanol), wherein adding has 0.25mg/mL N,O-Diacetylmuramidase and 50 μ g/mL sodiumazide.After at room temperature 5 minutes, add 5mL and extract buffer B (1.5M NaCl, 100mM CaCl ₂, 100mM MgCl ₂, 0.02mg/mL DNA enzyme 1, proteinase inhibitor sheet (Complete_1697498): 1 pr.20mL damping fluid).Then with extracting solution under 15.000g centrifugal 30 minutes.With sample on the gained supernatant liquor to being filled with Ni ²⁺1mL metal chelate affinity chromatography (MCAC) post on.With pillar with the 2 volume buffer A washing that contains the 20mM imidazoles, subsequently with the hGK of the His-mark of 20 minutes gradient elution institutes combination of the buffer A that contains 20 to 500mM imidazoles.Utilize the SDS-gel electrophoresis to check each several part, merge the part that contains hGK (MW:52KDa).At last, utilize the gel-filtration step to carry out final refining and buffer-exchanged.The part that will contain hGK is loaded onto Superdex 75 (16/60) gel-filtration columns, with buffer B (25mM HEPES, pH8.0,1mM MgCl ₂, 150mM NaCl, 1mM dithiothreitol (DTT)) and wash-out.Check purified hGK with SDS-gel electrophoresis and MALDI mass spectrum, before freezing, add 20% glycerine at last.Yield from the 50mL culture of Escherichia coli is generally about 2-3mg hGK, purity＞90%.

Add test compound to aperture, final DMSO concentration is 2.5%, and add-on is enough to obtain the desired concn of compound, for example 1,5,10,25 or 50 μ M.Add glucose to ultimate density and be 2,5,10 or 15mM after, begin reaction.Measure and adopt 96 hole UV flat boards, used final mensuration volume is 200 μ l/ holes.Flat board is cultivated 5min down at 25 ℃, in SpectraMax, under 340nm, measure kinetics, measured once, measured 5 minutes in per 30 seconds.The result of every kind of compound represents with the activation multiple that the glucokinase activity is compared with the activation of glucokinase in not having the mensuration of compound, all deducts " blank ", does not just have glucokinase and does not have compound.Compound among each embodiment all shows the glucokinase activation in this assay method.Compound concentration is 30 μ M or the glucokinase specific activity that the produces when lower high 1.5 times compound of measurement result when not having compound, is regarded as the activator of glucokinase.

The glucose-sensitive of compound be under the compound concentration of 10 μ M and 5 with the glucose concn of 15mM under measure.

Although preferred embodiment describe and set forth invention with reference to some, but those skilled in the art will figure out, and can carry out various variations, modification and replacement, and not deviate from the spirit and scope of the present invention.For example, owing to accept the result of mammiferous responsiveness difference of the disease treatment of glucokinase defective mediation, the effective dose except preferred dose described herein also may be suitable for.Equally, the concrete pharmacology response of observing can according to and depend on selected particular active compounds or whether have pharmaceutical carrier and the preparation type that adopts and administering mode and different, according to target of the present invention and practice, in the expection difference on this class result or difference all are encompassed in.

Glucokinase activation measurement (II)

The mensuration of glycogen deposition in the rat hepatocytes that separates

By two step perfusion techniques, isolating hepatocytes from the rat of ad libitum access.The cell viability of assessing according to trypanblue exclusion method is all the time greater than 80%.With (Medium 199 (5.5mM glucose) in the basic medium of cell plating to the 96 hole flat boards that scribble collagen, be supplemented with 0.1 μ M dexamethasone, 100 units/mL penicillin, 100mg/mL Streptomycin sulphate, 2mM L-glutaminate and 1nM Regular Insulin), substratum contains 4%FCS, cell density is 30,000 cells/well.Substratum was changed to basic medium in 1 hour behind initial plating, purpose is to remove dead cell.After 24 hours substratum is changed to the basic medium that is supplemented with 9.5mM glucose and 10nM Regular Insulin, synthetic to induce glycogen, experiment was carried out at second day.With buffer A (117.6mM NaCl, 5.4mMKCl, the 0.82mM Mg of liver cell with preheating (37 ℃) ₂SO ₄, 1.5mM KH ₂PO ₄, 20mM HEPES, 9mM NaHCO ₃, 0.1%w/v HSA and 2.25mM CaCl ₂, pH7.4,37 ℃) and washing, in wherein containing the buffer A of test compound (for example 1,5,10,25,50 or 100 μ M) of 15mM glucose and progressive concentration, cultivated 180 minutes 100 μ L.Utilize standard technology to measure glycogen content (Agius, L.etal, Biochem J. 266, 91-102 (1990).The measurement result of the glycogen content that produces in being used in this assay method when not having compound has the compound of significant increase to be regarded as having activity in this assay method.

Glucokinase activation measurement (III)

Glucokinase activating agents stimulates the insulin secretion in the INS-1E cell

As Asfari M et al., Endocrinology, 130, 167-178 (1992) is described, and cultivating the glucose responding beta cell is INS-1E.Seed cells into then in the 96 porocyte culture plates, growing to density is about 5 * 10 ⁴Every hole.The stimulation of glucose dependency insulin secretion is test like this, namely under 2.5 to 15mM glucose concn, add or do not add glucokinase activity compound, concentration is 1,5,10,25,50 or 100 μ M for example, in Krebs Ringer Hepes damping fluid, cultivated 2 hours, collect supernatant liquor, measure insulin concentration (n=4) by ELISA.The compound that has significantly, increases in response to the insulin secretion of the glucose measurement result when not having compound that produces in being used in this assay method is regarded as having activity in this assay method.

Claims (32)

1. general formula (Ib) compound

Formula (Ib)

Wherein:

R ²⁴Be selected from the group of being formed by following groups:

Halogen ,-OR ²,-NR ²R ³, C _1-6-alkyl-Z-, R ⁶-W ¹-Z-and R ⁶-W ¹-C _1-6-alkylidene group-Z-;

R ²And R ³Be hydrogen or C independently of one another _1-6-alkyl;

R ⁶Be hydrogen or C _1-6-alkyl;

Z be direct key ,-O-,-S-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) SO ₂-,-C (O)-O-,-N (H) SO ₂N (H)-or-O-C (O)-;

W ¹Be direct key ,-O-,-C (O)-,-SO ₂-,-C (O) NH-,-NHC (O)-,-N (H) SO ₂-,-C (O)-O-or-O-C (O)-;

L ¹Be key ,-D-C _1-6-alkylidene group-E-,-O-,-C (O)-,-N (R1 ¹)-or-C (=N-OR1 ²);

D be direct key or-O-;

E be direct key or-O-;

R1 ¹Be hydrogen;

R ¹The 2nd, hydrogen;

G ¹Be C _1-6-alkyl, C _2-6-thiazolinyl, C _2-6-alkynyl, C _3-10-cyclic hydrocarbon radical or C _3-10Heterocyclic radical, they are replaced by one or more substituting groups alternatively, described substituting group be selected from by-CN ,-CF ₃,-OCF ₃,-OR1 ⁸,-NR ¹8R1 ⁹, C _3-10-cyclic hydrocarbon radical and C _1-6The group that-alkyl is formed;

R ¹8 and R ¹9 is hydrogen or C independently of one another _1-6-alkyl;

L ²Be-N (R ²⁰)-;

R ²⁰Be hydrogen;

L ³Be-C (O)-;

R ¹Be hydrogen;

G ²Be

R ⁴³Be-C _1-6-alkylidene group-C (O) OR ⁵⁴

R ⁵⁴Be hydrogen, methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl, the tertiary butyl, 3-amyl group, 2-amyl group or 3-methyl-butyl;

Perhaps its pharmacy acceptable salt.

2. according to the compound of claim 1, R wherein ²⁴Be selected from the group of being formed by F, Cl, Br and methyl.

3. according to the compound of claim 1, R wherein ²Be hydrogen.

4. according to the compound of claim 1, R wherein ³Be hydrogen.

5. according to the compound of claim 1, wherein Z be direct key ,-NHC (O)-or-NHS (O) ₂-.

6. according to the compound of claim 1, R wherein ⁶Be hydrogen.

7. according to the compound of claim 1, W wherein ¹Be direct key or-C (O)-O-.

8. according to the compound of claim 7, W wherein ¹It is direct key.

9. according to the compound of claim 1, L wherein ¹Be-O-.

10. according to the compound of claim 1, L wherein ¹It is a key.

11. according to the compound of claim 1, wherein L ¹Be-C (O)-.

12. according to the compound of claim 1, wherein D is direct key.

13. according to the compound of claim 1, wherein D is-O-.

14. according to the compound of claim 1, wherein E is direct key.

15. according to the compound of claim 1, wherein E is-O-.

16. according to the compound of claim 1, wherein G ¹Be selected from by methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl, the tertiary butyl, 3-amyl group, 2-amyl group, 3-methyl-butyl, 2-propenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, oxetanyl, tetrahydrofuran base, THP trtrahydropyranyl, azetidinyl, pyrrolidyl, piperidyl, six hydrogen azepines

Base, thiacyclopentane base, tetrahydro thiapyran base, thia suberane base, 1,4-oxathiane base, 1,3-dioxolane base, 1,2-dithiolane base, 1,3-dithiolane base, hexahydro-pyridazine base, imidazolidyl, 1,3-two Alkyl, morpholinyl, 1,3-dithiane base, 1,4-two

Alkyl, 1, the group that 4-dithiane base and parathiazan base are formed.

17. according to the compound of claim 16, wherein G ¹Be selected from by methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl, the tertiary butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberane base, tetrahydrofuran base, THP trtrahydropyranyl, pyrrolidyl, piperidyl, six hydrogen azepines

The group that base, thiacyclopentane base, tetrahydro thiapyran base and thia suberane base are formed.

18. according to the compound of claim 17, wherein G ¹Be selected from by methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, cyclopentyl, cyclohexyl, tetrahydrofuran base, THP trtrahydropyranyl, piperidyl and six hydrogen azepines

The group that base is formed.

19. according to the compound of claim 18, wherein G ¹Be selected from the group of being formed by isobutyl-, cyclopentyl and piperidyl.

20. according to the compound of claim 19, wherein G ¹It is isobutyl-.

21. according to the compound of claim 19, wherein G ¹It is cyclopentyl.

22. according to the compound of claim 19, wherein G ¹It is piperidyl.

23. according to the compound of claim 1, wherein R1 ⁸And R ¹The 9th, hydrogen.

24. according to the compound of claim 1, wherein R ⁴³Be-CH ₂-C (O) OR ⁵⁴

25. according to the compound of claim 1, wherein R ⁵⁴Be hydrogen, methyl, ethyl, propyl group, butyl, sec.-propyl, isobutyl-, sec-butyl or the tertiary butyl.

26. according to the compound of claim 25, wherein R ⁵⁴Be hydrogen, methyl or ethyl.

27. according to the compound of claim 26, wherein R ⁵⁴Be hydrogen.

28. according to the compound of claim 1, wherein said compound is { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } acetic acid, perhaps its pharmacy acceptable salt.

29. according to the compound of claim 28, wherein said compound is { 2-[3-(2-pentamethylene carbonyl-4-methyl-phenyl)-urea groups]-thiazole-4-yl } acetic acid.

30. according to the compound of claim 1, wherein said compound is { 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid, perhaps its pharmacy acceptable salt.

31. according to the compound of claim 30, wherein said compound is { 2-[3-(4-methyl-2-[2-methyl propoxy-] phenyl)-urea groups]-thiazole-4-yl }-acetic acid.

32. pharmaceutical composition, its comprise at least a according to any one compound of claim 1 to 31 as activeconstituents, and one or more pharmaceutically acceptable carrier or vehicle.