WO2006135826A1 - Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof - Google Patents

Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof Download PDF

Info

Publication number
WO2006135826A1
WO2006135826A1 PCT/US2006/022651 US2006022651W WO2006135826A1 WO 2006135826 A1 WO2006135826 A1 WO 2006135826A1 US 2006022651 W US2006022651 W US 2006022651W WO 2006135826 A1 WO2006135826 A1 WO 2006135826A1
Authority
WO
WIPO (PCT)
Prior art keywords
indazol
trifluoro
fluorophenyl
propan
phenyl
Prior art date
Application number
PCT/US2006/022651
Other languages
French (fr)
Inventor
Ingo Andreas Mugge
Michael Jason Burke
Mark Stephen Ralph
David S. Thomson
Abdelhakim Hammach
Jennifer A. Kowalski
Joerg Martin Bentzien
Original Assignee
Boehringer Ingelheim International Gmbh
Boehringer Ingelheim Pharma Gmbh & Co. Kg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim International Gmbh, Boehringer Ingelheim Pharma Gmbh & Co. Kg filed Critical Boehringer Ingelheim International Gmbh
Priority to CA002610588A priority Critical patent/CA2610588A1/en
Priority to EP06772813A priority patent/EP1893588A1/en
Priority to BRPI0611620-5A priority patent/BRPI0611620A2/en
Priority to CN2006800205382A priority patent/CN101193869B/en
Priority to AU2006257861A priority patent/AU2006257861A1/en
Priority to MX2007014811A priority patent/MX2007014811A/en
Priority to NZ564696A priority patent/NZ564696A/en
Priority to JP2008515997A priority patent/JP2008543780A/en
Publication of WO2006135826A1 publication Critical patent/WO2006135826A1/en
Priority to IL187976A priority patent/IL187976A0/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/04—Drugs for disorders of the respiratory system for throat disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • C07D249/18—Benzotriazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention relates to glucocorticoid mimetics or ligands, methods of making such compounds, their use in pharmaceutical compositions, and their use in modulating the glucocorticoid receptor function, treating disease-states or conditions mediated by the glucocorticoid receptor function in a patient in need of such treatment, and other uses.
  • Glucocorticoids a class of corticosteroids, are endogenous hormones with profound effects on the immune system and multiple organ systems. They suppress a variety of immune and inflammatory functions by inhibition of inflammatory cytokines such as IL-I, IL-2, IL-6, and TNF, inhibition of arachidonic acid metabolites including prostaglandins and leukotrienes, depletion of T-lymphocytes, and reduction of the expression of adhesion molecules on endothelial cells (PJ. Barnes, Clin. ScL, 1998, 94, PP- 557-572; PJ. Barnes et al, Trends Pharmacol. ScL, 1993, 14, pp. 436-441). In addition to these effects, glucocorticoids stimulate glucose production in the liver and catabolism of proteins, play a role in electrolyte and water balance, reduce calcium absorption, and inhibit osteoblast function.
  • IL-I IL-I
  • IL-2 interleukin-2
  • IL-6 interleukin-6
  • glucocorticoids The anti-inflammatory and immune suppressive activities of endogenous glucocorticoids have stimulated the development of synthetic glucocorticoid derivatives including dexamethasone, prednisone, and prednisolone (L. Parente, Glucocorticoids, NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, pp. 35-54).
  • rheumatic diseases such as rheumatoid arthritis, juvenile arthritis, and ankylosing spondylitis
  • dermatological diseases including psoriasis and pemphigus
  • allergic disorders including allergic rhinitis, atopic dermatitis, and contact dermatitis
  • pulmonary conditions including asthma and chronic obstructive pulmonary disease (COPD)
  • COPD chronic obstructive pulmonary disease
  • Crohn disease ulcerative colitis
  • systemic lupus erythematosus autoimmune chronic active hepatitis
  • osteoarthritis tendonitis
  • bursitis J. Toogood, Glucocorticoids, NJ. Goulding and RJ.
  • the effects of glucocorticoids are mediated at the cellular level by the glucocorticoid receptor (R.H. Oakley and J. Cidlowski, Glucocorticoids, NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, pp. 55-80).
  • the glucocorticoid receptor is a member of a class of structurally related intracellular receptors that when coupled with a ligand can function as a transcription factor that affects gene expression (R.M. Evans, Science, 1988, 240, pp. 889-895).
  • Other members of the family of steroid receptors include the mineralocorticoid, progesterone, estrogen, and androgen receptors.
  • glucocorticoids In addition to the effects mentioned above for glucocorticoids, hormones that act on this receptor family have a profound influence on body homeostasis, mineral metabolism, the stress response, and development of sexual characteristics. Glucocorticoids. NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, is hereby incorporated by reference in its entirety to better describe the state of the art.
  • transactivation the translocation of the ligand-bound glucocorticoid receptor to the nucleus is followed by binding to glucocorticoid response elements (GREs) in the promoter region of side effect-associated genes, for example, phosphoenolpyruvate carboxy kinase (PEPCK) in the case of increased glucose production.
  • GREs glucocorticoid response elements
  • PEPCK phosphoenolpyruvate carboxy kinase
  • the anti-inflammatory effects are thought to be due to a process called transrepression.
  • transrepression is a process independent of DNA binding that results from inhibition of NF-IdB and AP-I -mediated pathways, leading to down regulation of many inflammatory and immune mediators. Additionally, it is believed that a number of the observed side effects may be due to the cross- reactivity of the currently available glucocorticoids with other steroid receptors, particularly the mineralocorticoid and progesterone receptors.
  • ligands for the glucocorticoid receptor that are highly selective and, upon binding, can dissociate the transactivation and transrepression pathways, providing therapeutic agents with a reduced side effect profile.
  • Assay systems to determine effects on transactivation and transrepression have been described (e.g., CM. Bamberger and H.M. Schulte, Eur. J. Clin. Invest., 2000, 30 (suppl. 3), pp. 6-9).
  • Selectivity for the glucocorticoid receptor may be determined by comparing the binding affinity for this receptor with that of other steroid family receptors including those mentioned above.
  • Glucocorticoids also stimulate the production of glucose in the liver by a process called gluconeogenesis and it is believed that this process is mediated by transactivation events. Increased glucose production can exacerbate type II diabetes, therefore a compound that selectivity inhibited glucocorticoid mediated glucose production may have therapeutic utility in this indication (J.E. Freidman et al., J. Biol. Chem., 1997, 272, pp. 31475-31481).
  • PCT International Publication No. WO 04/093805 discloses selective spirocyclic glucocorticoid receptor modulators potentially useful in treating many inflammatory diseases, including rheumatoid arthritis and Crohn's disease.
  • PCT International Publication No. WO 04/026248 discloses octahydro-2H-naphtho[l,2-/jindole-4-carboxamide derivatives as selective glucocorticoid receptor modulators potentially useful in treating for the treatment of many inflammatory diseases, including rheumatoid arthritis and Crohn's disease.
  • WO 04/075840 discloses selective non-steroidal glucocorticoid receptor modulator with potential use as anti-inflammatory agents possessing advantages over the glucocorticoid ligands with respect to side-effects, efficacy, and toxicity.
  • PCT International Publication No. WO 03/086294 discloses lH-benzo[/]indazol-5-yl derivatives as selective glucocorticoid receptor modulators potentially useful in treating for the treatment of many inflammatory diseases, including rheumatoid arthritis and Crohn's disease.
  • 2005/0054700 disclose non-steroidal ligands for the glucocorticoid receptor, potentially useful in treating metabolic and inflammatory diseases.
  • PCT International Publication No. WO 99/33786 discloses triphenylpropanamide compounds with potential use in treating inflammatory diseases.
  • PCT International Publication No. WO 00/66522 describes nonsteroidal compounds as selective modulators of the glucocorticoid receptor potentially useful in treating metabolic and inflammatory diseases.
  • PCT International Publication No. WO 99/41256 describes tetracyclic modulators of the glucocorticoid receptor potentially useful in treating immune, autoimmune, and inflammatory diseases.
  • 5,688,810 describes various non-steroidal compounds as modulators of glucocorticoid and other steroid receptors.
  • PCT International Publication No. WO 99/63976 describes a non-steroidal, liver- selective glucocorticoid antagonist potentially useful in the treatment of diabetes.
  • PCT International Publication No. WO 00/32584 discloses non-steroidal compounds having anti- inflammatory activity with dissociation between anti-inflammatory and metabolic effects.
  • PCT International Publication No. WO 98/54159 describes non-steroidal cyclically substituted acylanilides with mixed gestagen and androgen activity.
  • a compound that is found to interact with the glucocorticoid receptor in a binding assay could be an agonist or an antagonist.
  • the agonist properties of the compound could be evaluated in the transactivation or transrepression assays described above.
  • the compound may be found to have antagonist activity.
  • glucocorticoids stimulate glucose production in the liver.
  • a ligand for the glucocorticoid receptor that is found to be an antagonist may be useful, inter alia, for treating or preventing diabetes.
  • the instant invention is directed to compounds of Formula (IA)
  • R 1 is aryl, heteroaryl, or C 3 -C 7 cycloalkyl each optionally independently substituted with one to three substituent groups selected from Ci-C 3 alkyl, hydroxy, halogen, oxo, methoxy, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a methyl group; or thiomethyl wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;
  • R 2 is hydrogen or a halogen
  • a and B are each independently CH or N;
  • C and E are each independently a bond or a -CH 2 -;
  • D is -CR 4 R 5 -, where R 4 is -CF 3 and R 5 is -OH; and is C 1 -C ⁇ alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, NR 6 R 7 , OR 8 , or SR 9 , each optionally independently substituted with one to three substituent groups,
  • each substituent group of R 3 is independently aryl, heteroaryl, heterocyclyl, C 1 -C 5 alkyl, Cj-C 5 alkenyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C 5 alkanoyloxy, Ci-C 5 alkanoyl, aroyl, Ci-C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, Ci-C 5 alkylaminocarbonyloxy, Ci-C 5 dialkylaminocarbonyloxy, Cj-C 5 alkanoylamino, Ci-C 5 alkoxycarbonylamino, Ci-C 5 alkylsulfonylamino, aminosulfonyl, Ci-C 5 alkylaminosulfonyl, CpC 5 dialkylaminosulfonyl, Ci-C 5 alkyloxy, aryloxy,
  • each substituent group of R 3 is optionally independently substituted with one to three substituents selected from aryl, heteroaryl, heterocyclyl, acyl, Cj-C 5 alkyl, Ci-C 5 alkanoyloxy, Cj-C 5 alkanoyl, Ci-C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, Ci-C 5 alkylsulfonylamino, aminosulfonyl, Ci-C 5 alkylaminosulfonyl, Cj-C 5 dialkylaminosulfonyl, Cj-C 5 alkyloxy, Cj-C 5 cycloalkyl, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Cj-C 5 alkyl, or Cj-C 5 alkyl,
  • R 6 is a hydrogen or C 1 -C 3 alkyl
  • R 7 , R 8 , and R 9 are each independently Ci-C 5 alkyl, CpC 5 alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl optionally independently substituted with one to three substituent groups,
  • each substituent group of R 7 , R 8 , and R 9 is independently heteroaryl, heterocyclyl, Ci-C 5 alkyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C 5 alkanoyloxy, Ci-C 5 alkanoyl, aroyl, C 1 -C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C 1 -C 5 alkylaminocarbonyloxy, C1-C5 dialkylaminocarbonyloxy, C 1 -Cs alkanoylamino, C 1 -C 5 alkoxycarbonylamino, C 1 - C 5 alkylsulfonylatnino, aminosulfonyl, Ci-C 5 alkylaminosulfonyl, Ci-C 5 dialkylaminosulfonyl, C 1 -C 5 alkyloxy
  • each substituent group of R 7 , R 8 , and R 9 is optionally independently substituted with one to three substituent groups selected from heteroaryl, heterocyclyl, acyl, Ci-C 5 alkyl, Ci-C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, C 1 -C 5 alkylsulfonylamino, aminosulfonyl, CpC 5 alkylaminosulfonyl, Ci-C 5 dialkylaminosulfonyl, C 1 -C 5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C 5 alkyl, or Ci-C 5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • One aspect of the invention includes compounds of Formula (IA), wherein:
  • R 1 is aryl or heteroaryl optionally independently substituted with one to three substituent groups selected from hydroxy, halogen, or oxo;
  • R 2 is hydrogen
  • C is a bond and E is a bond or -CH 2 -,
  • One aspect of the invention includes compounds of Formula (IA), wherein:
  • R 1 is a phenyl optionally substituted with one to three halogen groups
  • A is N;
  • R 3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1 ,2,3,4-tetrahydroisoquinoline, N-ethyl-iV -methylbenzene- 1 ,2-diamine,
  • 1,2,3,4-tetrahydroquinoline NR 6 R 7 , OR 8 , or SR 9 group, each optionally independently substituted with one to three substituent groups,
  • each substituent group of R 3 is independently C 1 -Cs alkyl, heteroaryl, heterocyclyl, acyl, C 1 -C 5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C 1 -Cs alkyl, C 1 -Cs alkenyl, carboxyl, or C 1 -Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • each substituent group of R 3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C 1 -Cs alkyl, C 1 -Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C 1 -Cs alkyl, or C 1 -Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • R 6 is a hydrogen or a methyl group
  • R 7 , R 8 , and R 9 are each independently a phenyl, naphthyl, pyridyl, pyrimidyl, quinoline, isoquinoline, or indolyl optionally independently substituted with one to three substituent groups, wherein each substituent group of R 7 , R 8 , and R 9 is independently heterocyclyl, Ci-C 5 alkyl, cycloalkyl, acyl, Ci-C 5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C 5 alkyl, or Ci-C 5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • One aspect of the above embodiment includes compounds of Formula (IA), wherein:
  • R 3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1,2,3,4-tetrahydroisoquinoline, N-ethyl-N'-methylbenzene-l,2-diamine, or 1 ,2,3 ,4-tetrahydroquinoline,
  • each substituent group of R 3 is independently Cj-C 5 alkyl, C 1 -C 5 alkenyl, carboxyl, acyl, Ci-C 5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C 5 alkyl, or Ci-C 5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • each substituent group of R 3 is optionally independently substituted with one to three substituents selected from CpC 5 alkyl, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C 5 alkyl, or Ci-C 5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • More preferred compounds of Formula (IA) include the following:
  • the invention also provides a method of making a compound of Formula (IA)
  • C is CH 2
  • D is CR 4 R 5 (where R 4 is CF 3 and R 5 is OH)
  • E is a bond
  • A, B, R 1 , R 2 , and R 3 are as defined above, the method comprising: (a) reacting the nitrile of Formula (II) with a suitable reducing agent, such as diisopropyl aluminum hydride, in a suitable solvent, such as dichloromethane, to provide an aldehyde of Formula (III)
  • a suitable reducing agent such as diisopropyl aluminum hydride
  • a compound of Formula (IA), wherein C is a bond, and A, B, D, E, R 1 , R 2 , and R 3 are as defined above may be prepared by starting from the aldehyde of Formula (III) and following steps (e), (f), and (g).
  • the invention also provides a method for making a compound of Formula (IA), wherein R 3 is NR 6 R 7 , OR 8 , or SR 9 , C is CH 2 , D is CR 4 R 5 (where R 4 is CF 3 and R 5 is OH), E is CH 2 , and A, B, R 1 , and R 2 are as defined above, the method comprising: (a') reacting a ketone of Formula (IX) with a sulfur ylide of Formula (XI) in the presence of a suitable base, such as sodium hydride, in a suitable solvent, such as THF, to provide an epoxide of Formula (XII)
  • a compound of Formula (IA), wherein C is CH 2 , D is CR 4 R 5 (where R 4 is CF 3 and R 5 is OH), and E is a bond may be made by starting from the aldehyde of Formula (VII) using the following process:
  • the instant invention is also directed to compounds of Formula (IB)
  • R 1 is aryl, heteroaryl or C 3 -C 7 cycloalkyl each optionally independently substituted with one to three substituent groups selected from Ci-C 3 alkyl, hydroxy, halogen, oxo, methoxy, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a methyl group, or thiomethyl wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;
  • R 2 is hydrogen or a halogen
  • a and B are each independently CH or N;
  • C and E are each independently a bond or a -CH 2 -;
  • R 4 is Ci-Cs alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, carbocycle, heterocyclyl, aryl, heteroaryl, carbocycle-C[-C 8 alkyl, aryl-Q-Cg alkyl, aryl-Ci-C 8 haloalkyl, heterocyclyl-Ci-C 8 alkyl, heteroaryl-Ci-C 8 alkyl, carbocycle-C 2 -C8 alkenyl, aryl-C 2 -C 8 alkenyl, heterocyclyl-C2-C 8 alkenyl, or heteroaryl-C 2 -C 8 alkenyl, each optionally independently substituted with one to three substituent groups,
  • each substituent group of R 4 is independently Ci-C 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, Ci-C 3 alkoxy, aminocarbonyl, Ci-C 3 alkylaminocarbonyl, C 1 -C 3 dialkylaminocarbonyl, halogen, hydroxy, carboxy, cyano, trifiuoromethyl, nitro, or Ci- C 3 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein R 4 cannot be trifiuoromethyl,
  • R 5 is -OH
  • R 3 is Ci-C 6 alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, NR 6 R 7 , OR 8 , or SR 9 , each optionally independently substituted with one to three substituent groups,
  • each substituent group of R 3 is independently aryl, heteroaryl, heterocyclyl,
  • each substituent group of R 3 is optionally independently substituted with one to three substituents selected from aryl, heteroaryl, heterocyclyl, acyl, Ci-C 5 alkyl, Cj-C 5 alkanoyloxy, Q-C 5 alkanoyl, Ci-C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, Ci-C 5 alkylsulfonylamino, aminosulfonyl, Ci-C 5 alkylaminosulfonyl, Ci-C 5 dialkylaminosulfonyl, Ci-C 5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C J -C 5 alkyl, Ci-C 5 cycloalkyl, or Ci-C 5 alkylthio wherein
  • R 6 is a hydrogen or C 1 -C 3 alkyl
  • R 7 , R 8 , and R 9 are each independently Cj-C 5 alkyl, Ci-C 5 alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl optionally independently substituted with one to three substituent groups,
  • each substituent group of R 7 , R 8 , and R 9 is independently heteroaryl, heterocyclyl, Ci-C 5 alkyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C 5 alkanoyloxy, C 1 -C 5 alkanoyl, aroyl, Cj-C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, Ci-C 5 alkylaminocarbonyloxy, Ci-C 5 dialkylaminocarbonyloxy, Cj-C 5 alkanoylamino, Cj-C 5 alkoxycarbonylamino, Cj-C 5 alkylsulfonylamino, aminosulfonyl, Cj-C 5 alkylaminosulfonyl, Cj-C 5 dialkylaminosulfonyl, Ci-C 5 alkyloxy, aryloxy,
  • each substituent group of R 7 , R 8 , and R 9 is optionally independently substituted with one to three substituent groups selected from heteroaryl, heterocyclyl, acyl, C 1 -Cs alkyl, C 1 -C 5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, C 1 -C 5 alkylsulfonylamino, aminosulfonyl, C 1 -C 5 alkylaminosulfonyl, Ci-C 5 dialkylaminosulfonyl, Ci-C 5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C 5 alkyl, or Ci-C 5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulf
  • One aspect of the invention includes compounds of Formula (IB), wherein:
  • R 1 is aryl or heteroaryl optionally substituted with one to three substituent groups selected from hydroxy, halogen, or oxo;
  • R 2 is hydrogen
  • E is a bond or -CH 2 -
  • R 4 is C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 3 -C 6 cycloalkyl, phenyl, C 3 -C 6 cycloalkyl-C r C 3 alkyl, phenyl-C]-C 3 alkyl, phenyl-Ci-C 3 haloalkyl, C 3 -C 6 cycloalkyl-C 2 -C 3 alkenyl, phenyl-C 2 -
  • each substituent group of R 4 is independently CpC 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, Cj-C 3 alkoxy, aminocarbonyl, Cj-C 3 alkylaminocarbonyl, Cj-C 3 dialkylaminocarbonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or Q- C 3 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein R 4 cannot be trifluoromethyl, and
  • R 5 is -OH
  • One aspect of the invention includes compounds of Formula (IB), wherein:
  • R 1 is a phenyl optionally substituted with one to three halogen groups
  • A is N;
  • B is CH
  • R 4 is C 1 -C 5 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl-methyl-, or benzyl, each optionally independently substituted with one to three substituent groups,
  • each substituent group of R 4 is independently methyl, methoxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or hydroxy, wherein R 4 cannot be trifluoromethyl, and
  • R 5 is -OH
  • R 3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1,2,3,4-tetrahydroisoquinoline, or N-ethyl-JV-methylbenzene-l,2-diamine, 1,2,3,4-tetrahydroquinoline, NR 6 R 7 , OR 8 , or SR 9 ; each optionally independently substituted with one to three substituent groups,
  • each substituent group of R 3 is independently C 1 -Cs alkyl, heteroaryl, heterocyclyl, acyl, C 1 -C 5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C 1 -Cs alkyl, C 1 -Cs alkenyl, carboxyl, or C 1 -Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • each substituent group of R 3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C 1 -Cs alkyl, C 1 -Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C 1 -Cs alkyl, or C 1 -Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • R 6 is a hydrogen or a methyl group
  • R 7 , R 8 , and R 9 are each independently a phenyl, naphthyl, pyridyl, pyrimidyl, quinoline, isoquinoline, or indolyl optionally independently substituted with one to three substituent groups,
  • each substituent group of R 7 , R 8 , and R 9 is independently heterocyclyl, Ci-C 5 alkyl, cycloalkyl, acyl, C 1 -C 5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C 1 -Cs alkyl, or C 1 -Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • R 3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1,2,3,4-tetrahydroisoquinoline, or N-ethyl-iV-methylbenzene-l,2-diamine, 1 ,2,3 ,4-tetrahydroquinoline,
  • each substituent group of R 3 is independently Ci-C 5 alkyl, acyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C 1 -C 5 alkyl, C 1 -C 5 alkenyl, carboxyl, or C 1 -C 5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
  • each substituent group of R 3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C 1 -C 5 alkyl, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C 5 alkyl, or Q-
  • Preferred compounds of Formula (IB) include the following:
  • the invention also provides a method of making a compound of Formula (IB)
  • A, B, C, D, E, R 1 , R 2 , and R 3 are as defined above, the method comprising:
  • a compound of Formula (IB), wherein C is a bond or CH 2 , D is CR 4 R 5 (where R 5 is OH), and E is a bond, and A, B, R 1 , R 2 , R 3 , and R 4 are as defined above may be prepared by starting from the ketone of Formula (XV) using the following step:
  • the compounds according to the invention are formulated into pharmaceutical compositions comprising an effective amount, preferably a pharmaceutically effective amount, of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof, and a pharmaceutically acceptable excipient or carrier.
  • the invention also provides a method of modulating the glucocorticoid receptor function in a patient, the method comprising administering to the patient an effective amount of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
  • the invention further provides a method of treating a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
  • the invention also provides a method of treating a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
  • a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma
  • the invention provides a method of treating a disease characterized by inflammatory, allergic, or proliferative processes, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
  • the disease characterized by inflammatory, allergic, or proliferative processes is selected from: (i) lung diseases (ii) rheumatic diseases or autoimmune diseases or joint diseases (iii) allergic diseases (iv) vasculitis diseases (v) dermatological diseases (vi) renal diseases (vii) hepatic diseases (viii) gastrointestinal diseases (ix) procto logical diseases (x) eye diseases (xi) diseases of the ear, nose, and throat (ENT) area (xii) neurological diseases (xiii) blood diseases (xiv) tumor diseases (xv) endocrine diseases (xvi) organ and tissue transplantations and graft-versus-host diseases (xvii) severe states of shock (xviii) substitution therapy; and (xix) pain of inflammatory genesis.
  • the disease characterized by inflammatory, allergic, or proliferative processes is selected from: type I diabetes, osteoarthritis, Guillain-Barre syndrome, restenosis following percutaneous transluminal coronary angioplasty, Alzheimer disease, acute and chronic pain, atherosclerosis, reperfusion injury, bone resorption diseases, congestive heart failure, myocardial infarction, thermal injury, multiple organ injury secondary to trauma, acute purulent meningitis, necrotizing enterocolitis, and syndromes associated with hemodialysis, leukopheresis, and granulocyte transfusion.
  • the invention further provides methods of treating the disease-states or conditions mentioned above, in a patient in need of such treatment, the methods comprising sequentially or simultaneously administering to the patient: (a) an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof; and (b) a pharmaceutically acceptable glucocorticoid.
  • the invention further provides a method of assaying the glucocorticoid receptor function in a sample, comprising: (a) contacting the sample with a selected amount of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof; and (b) detecting the amount of the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof bound to glucocorticoid receptors in the sample.
  • the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof is labeled with a detectable marker selected from: a radiolabel, fluorescent tag, a chemiluminescent tag, a chromophore, and a spin label.
  • a detectable marker selected from: a radiolabel, fluorescent tag, a chemiluminescent tag, a chromophore, and a spin label.
  • the invention also provides a method of imaging the glucocorticoid receptor distribution in a sample or patient, the method comprising: (a) contacting the sample or administering to a patient a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof having a detectable marker (b) detecting the spatial distribution and amount of the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof having a detectable marker bound to glucocorticoid receptors in the sample or patient using an imaging means to obtain an image; and (c) displaying an image of the spatial distribution and amount of the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof having a detectable marker bound to glucocorticoid receptors in the sample.
  • the imaging means is selected from: radioscintigraphy, nuclear magnetic resonance imaging (MRJ), computed tomography (CT scan), or positron emission to
  • the invention also provides a kit for the in vitro diagnostic determination of the glucocorticoid receptor function in a sample, comprising: (a) a diagnostically effective amount of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof; and (b) instructions for use of the diagnostic kit.
  • C 1 -Ci O alkyl means an alkyl group or radical having 1 to 10 carbon atoms.
  • the term "lower” applied to any carbon-containing group means a group containing from 1 to 8 carbon atoms, as appropriate to the group (i.e., a cyclic group must have at least 3 atoms to constitute a ring).
  • alkylaryl means a monovalent radical of the formula AIk-Ar-
  • arylalkyl means a monovalent radical of the formula Ar-AIk- (where AIk is an alkyl group and Ar is an aryl group).
  • use of a term designating a monovalent radical where a divalent radical is appropriate shall be construed to designate the respective divalent radical and vice versa.
  • conventional definitions of terms control and conventional stable atom valences are presumed and achieved in all formulas and groups.
  • alkyl or "alkyl group” mean a branched or straight-chain saturated aliphatic hydrocarbon monovalent radical. This term is exemplified by groups such as methyl, ethyl, n- propyl, 1-methylethyl (isopropyl), ??-butyl, ⁇ -pentyl, 1,1 -dimethyl ethyl (tert-buty ⁇ ), and the like. It may be abbreviated "AIk”.
  • alkenyl or “alkenyl group” mean a branched or straight-chain aliphatic hydrocarbon monovalent radical containing at least one carbon-carbon double bond.
  • This term is exemplified by groups such as ethenyl, propenyl, w-butenyl, isobutenyl, 3-methylbut-2-enyl, «-pentenyl, heptenyl, octenyl, decenyl, and the like.
  • alkynyl or “alkynyl group” mean a branched or straight-chain aliphatic hydrocarbon monovalent radical containing at least one carbon-carbon triple bond. This term is exemplified by groups such as ethynyl, propynyl, »-butynyl, 2-butynyl, 3-methylbutynyl, n- pentynyl, heptynyl, octynyl, decynyl, and the like.
  • alkylene or "alkylene group” mean a branched or straight-chain saturated aliphatic hydrocarbon divalent radical having the specified number of carbon atoms. This term is exemplified by groups such as methylene, ethylene, propylene, «-butylene, and the like, and may alternatively and equivalently be denoted herein as -(alkyl)-.
  • alkenylene or "alkenylene group” mean a branched or straight-chain aliphatic hydrocarbon divalent radical having the specified number of carbon atoms and at least one carbon-carbon double bond. This term is exemplified by groups such as ethenylene, propenylene, «-butenylene, and the like, and may alternatively and equivalently be denoted herein as -(alkylenyl)-.
  • alkynylene or "alkynylene group” mean a branched or straight-chain aliphatic hydrocarbon divalent radical containing at least one carbon-carbon triple bond. This term is exemplified by groups such as ethynylene, propynylene, n-butynylene, 2-butynylene, 3- methylbutynylene, M-pentynylene, heptynylene, octynylene, decynylene, and the like, and may alternatively and equivalently be denoted herein as -(alkynyl)-.
  • alkoxy or "alkoxy group” mean a monovalent radical of the formula AIkO-, where AIk is an alkyl group. This term is exemplified by groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentoxy, and the like.
  • aryloxy means a monovalent radical of the formula ArO-, where Ar is aryl. This term is exemplified by groups such as phenoxy, naphthoxy, and the like.
  • alkylcarbonyl means a monovalent radical of the formula AIkC(O)-, where AIk is alkyl or hydrogen.
  • arylcarbonyl means a monovalent radical of the formula ArC(O)-, where Ar is aryl.
  • acyl or "acyl group” mean a monovalent radical of the formula RC(O)-, where R is a substituent selected from hydrogen or an organic substituent.
  • substituents include alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, and the like. As such, the terms comprise alkylcarbonyl groups and arylcarbonyl groups.
  • acylamino or "acylamino group” mean a monovalent radical of the formula RC(O)N(R)-, where each R is a substituent selected from hydrogen or a substituent group.
  • alkoxycarbonyl or "alkoxycarbonyl group” mean a monovalent radical of the formula AIkO-C(O)-, where AIk is alkyl.
  • exemplary alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, tert-butyloxycarbonyl, and the like.
  • aryloxycarbonyl or "aryloxycarbonyl group” mean a monovalent radical of the formula ArO-C(O)-, where Ar is aryl.
  • alkylcarbonyloxy or “alkylcarbonyloxy group” or “alkanoyloxy” or “alkanoyloxy group” mean a monovalent radical of the formula AIkC(O)O-, where AIk is alkyl.
  • arylcarbonyloxy or "arylcarbonyloxy group” or “aroyloxy” or “aroyloxy group” mean a monovalent radical of the formula ArC(O)O-, where Ar is aryl.
  • alkylaminocarbonyloxy or “alkylaminocarbonyloxy group” mean a monovalent radical of the formula R 2 NC(O)O-, where each R is independently hydrogen or lower alkyl.
  • alkoxycarbonylamino or “alkoxycarbonylamino group” mean a monovalent radical of the formula ROC(O)NH-, where R is lower alkyl.
  • alkylcarbonylamino or “alkylcarbonylamino group” or “alkanoylamino” or “alkanoylamino groups” mean a monovalent radical of the formula AIkC(O)NH-, where AIk is alkyl.
  • exemplary alkylcarbonylamino groups include acetamido (CHsC(O)NH-).
  • alkylaminocarbonyloxy or “alkylaminocarbonyloxy group” mean a monovalent radical of the formula AlIcNHC(O)O-, where AIk is alkyl.
  • amino or “amino group” mean an -NH 2 group.
  • alkylamino or "alkylamino group” mean a monovalent radical of the formula (AIk)NH-, where AIk is alkyl.
  • exemplary alkylamino groups include methylamino, ethylamino, propylamino, butylamino, tert-butylamino, and the like.
  • dialkylamino or "dialkylamino group” mean a monovalent radical of the formula (AIk)(AIk)N-, where each AIk is independently alkyl.
  • exemplary dialkylamino groups include dimethylamino, methylethylamino, diethylamino, dipropylamino, ethylpropylamino, and the like.
  • substituted amino or “substituted amino group” mean a monovalent radical of the formula -NR 2 , where each R is independently a substituent selected from hydrogen or the specified substituents (but where both Rs cannot be hydrogen).
  • substituents include alkyl, alkanoyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, and the like.
  • alkoxycarbonylamino or “alkoxycarbonylamino group” mean a monovalent radical of the formula AIkOC(O)NH-, where AIk is alkyl.
  • ureido or “ureido group” mean a monovalent radical of the formula R 2 NC(O)NH-, where each R is independently hydrogen or alkyl.
  • halo means one or more hydrogen atoms of the group are replaced by halogen groups.
  • haloalkyl or "haloalkyl group” mean a branched or straight-chain saturated aliphatic hydrocarbon monovalent radical, wherein one or more hydrogen atoms thereof are each independently replaced with halogen atoms. This term is exemplified by groups such as chloromethyl, 1,2-dibromoethyl, 1,1,1-trifluoropropyl, 2-iodobutyl, l-chloro-2-bromo-3- fluoropentyl, and the like.
  • sulfanyl means a divalent radical of the formula -S-.
  • alkylthio or "alkylthio group” mean a monovalent radical of the formula AIkS-, where AIk is alkyl.
  • exemplary groups include methylthio, ethylthio, «-propylthio, isopropylthio, «-butylthio, and the like.
  • arylthio or "arylthio group” mean a monovalent radical of the formula ArS-, where Ar is aryl.
  • sulfinyl means a divalent radical of the formula -SO-.
  • sulfonyl or "sulfonyl group” mean a divalent radical of the formula -SO 2 -.
  • sulfonylamino or “sulfonylamino group” mean a divalent radical of the formula -SO 2 NR-, where R is a hydrogen or a substituent group.
  • aminonosulfonyl or “aminosulfonyl group” mean a monovalent radical of the formula NR 2 SO 2 -, where R is each independently a hydrogen or a substituent group.
  • carbocycle or “carbocyclic group” mean a stable aliphatic 3- to 15-membered monocyclic or polycyclic monovalent or divalent radical consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7- membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the carbocycle may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure.
  • the term comprises cycloalkyl (including spiro cycloalkyl), cycloalkylene, cycloalkenyl, cycloalkenylene, cycloalkynyl, and cycloalkynylene, and the like.
  • cycloalkyl or "cycloalkyl group” mean a stable aliphatic saturated 3- to 15- membered monocyclic or polycyclic monovalent radical consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7- membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the cycloalkyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure.
  • Exemplary cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, norbornane, adamantyl, tetrahydronaphthyl (tetralin), 1-decalinyl, bicyclo[2.2.2]octanyl, 1-methylcyclopropyl, 2-methylcyclopentyl, 2- methylcyclooctyl, and the like.
  • cycloalkenyl or “cycloalkenyl group” mean a stable aliphatic 5- to 15-membered monocyclic or polycyclic monovalent radical having at least one carbon-carbon double bond and consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic ring.
  • the cycloalkenyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure.
  • exemplary cycloalkenyl groups include cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, norbornenyl, 2- methylcyclopentenyl, 2-methylcyclooctenyl, and the like.
  • cycloalkynyl or “cycloalkynyl group” mean a stable aliphatic 8- to 15-membered monocyclic or polycyclic monovalent radical having at least one carbon-carbon triple bond and consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 8- to 10-membered monocyclic or 12- to 15-membered bicyclic ring.
  • the cycloalkynyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure.
  • Exemplary cycloalkynyl groups include, cyclooctynyl, cyclononynyl, cyclodecynyl, 2-methylcyclooctynyl, and the like.
  • cycloalkylene or "cycloalkylene group” mean a stable saturated aliphatic 3- to 15- membered monocyclic or polycyclic divalent radical consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7- membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the cycloalkyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure.
  • Exemplary cycloalkylene groups include cyclopentylene, and the like.
  • cycloalkenylene or "cycloalkenylene group” mean a stable aliphatic 5- to 15- membered monocyclic or polycyclic divalent radical having at least one carbon-carbon double bond and consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic ring.
  • the cycloalkenylene ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure.

Abstract

Compounds of Formula (IA) and (IB) wherein R1, R2, R3, A, B, C, D, and E are as defined herein, or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

Description

GLUCOCORTICOID MIMETICS. METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS. AND USES THEREOF
Field of the Invention The present invention relates to glucocorticoid mimetics or ligands, methods of making such compounds, their use in pharmaceutical compositions, and their use in modulating the glucocorticoid receptor function, treating disease-states or conditions mediated by the glucocorticoid receptor function in a patient in need of such treatment, and other uses.
Background of the Invention
Glucocorticoids, a class of corticosteroids, are endogenous hormones with profound effects on the immune system and multiple organ systems. They suppress a variety of immune and inflammatory functions by inhibition of inflammatory cytokines such as IL-I, IL-2, IL-6, and TNF, inhibition of arachidonic acid metabolites including prostaglandins and leukotrienes, depletion of T-lymphocytes, and reduction of the expression of adhesion molecules on endothelial cells (PJ. Barnes, Clin. ScL, 1998, 94, PP- 557-572; PJ. Barnes et al, Trends Pharmacol. ScL, 1993, 14, pp. 436-441). In addition to these effects, glucocorticoids stimulate glucose production in the liver and catabolism of proteins, play a role in electrolyte and water balance, reduce calcium absorption, and inhibit osteoblast function.
The anti-inflammatory and immune suppressive activities of endogenous glucocorticoids have stimulated the development of synthetic glucocorticoid derivatives including dexamethasone, prednisone, and prednisolone (L. Parente, Glucocorticoids, NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, pp. 35-54). These have found wide use in the treatment of inflammatory, immune, and allergic disorders including rheumatic diseases such as rheumatoid arthritis, juvenile arthritis, and ankylosing spondylitis, dermatological diseases including psoriasis and pemphigus, allergic disorders including allergic rhinitis, atopic dermatitis, and contact dermatitis, pulmonary conditions including asthma and chronic obstructive pulmonary disease (COPD), and other immune and inflammatory diseases including Crohn disease, ulcerative colitis, systemic lupus erythematosus, autoimmune chronic active hepatitis, osteoarthritis, tendonitis, and bursitis (J. Toogood, Glucocorticoids, NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, pp. 161-174). They have also been used to help prevent rejection in organ transplantation. Unfortunately, in addition to the desired therapeutic effects of glucocorticoids, their use is associated with a number of adverse side effects, some of which can be severe and life- threatening. These include alterations in fluid and electrolyte balance, edema, weight gain, hypertension, muscle weakness, development or aggravation of diabetes mellitus, and osteoporosis. Therefore, a compound that exhibited a reduced side effect profile while maintaining the potent anti-inflammatory effects would be particularly desirable, especially when treating a chronic disease.
The effects of glucocorticoids are mediated at the cellular level by the glucocorticoid receptor (R.H. Oakley and J. Cidlowski, Glucocorticoids, NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, pp. 55-80). The glucocorticoid receptor is a member of a class of structurally related intracellular receptors that when coupled with a ligand can function as a transcription factor that affects gene expression (R.M. Evans, Science, 1988, 240, pp. 889-895). Other members of the family of steroid receptors include the mineralocorticoid, progesterone, estrogen, and androgen receptors. In addition to the effects mentioned above for glucocorticoids, hormones that act on this receptor family have a profound influence on body homeostasis, mineral metabolism, the stress response, and development of sexual characteristics. Glucocorticoids. NJ. Goulding and RJ. Flowers (eds.), Boston: Birkhauser, 2001, is hereby incorporated by reference in its entirety to better describe the state of the art.
A molecular mechanism which accounts for the beneficial anti-inflammatory effects and the undesired side effects has been proposed (e.g., S. Heck et al, EMBO J, 1994, 17, pp. 4087- 4095; H.M. Reichardt et al, Cell, 1998, 93, pp. 531-541; F. Tronche et al, Curr. Opin. in Genetics and Dev., 1998, 8., pp. 532-538). Many of the metabolic and cardiovascular side effects are thought to be the result of a process called transactivation. In transactivation, the translocation of the ligand-bound glucocorticoid receptor to the nucleus is followed by binding to glucocorticoid response elements (GREs) in the promoter region of side effect-associated genes, for example, phosphoenolpyruvate carboxy kinase (PEPCK) in the case of increased glucose production. The result is an increased transcription rate of these genes which is believed to result, ultimately, in the observed side effects. The anti-inflammatory effects are thought to be due to a process called transrepression. In general, transrepression is a process independent of DNA binding that results from inhibition of NF-IdB and AP-I -mediated pathways, leading to down regulation of many inflammatory and immune mediators. Additionally, it is believed that a number of the observed side effects may be due to the cross- reactivity of the currently available glucocorticoids with other steroid receptors, particularly the mineralocorticoid and progesterone receptors.
Thus, it may be possible to discover ligands for the glucocorticoid receptor that are highly selective and, upon binding, can dissociate the transactivation and transrepression pathways, providing therapeutic agents with a reduced side effect profile. Assay systems to determine effects on transactivation and transrepression have been described (e.g., CM. Bamberger and H.M. Schulte, Eur. J. Clin. Invest., 2000, 30 (suppl. 3), pp. 6-9). Selectivity for the glucocorticoid receptor may be determined by comparing the binding affinity for this receptor with that of other steroid family receptors including those mentioned above.
Glucocorticoids also stimulate the production of glucose in the liver by a process called gluconeogenesis and it is believed that this process is mediated by transactivation events. Increased glucose production can exacerbate type II diabetes, therefore a compound that selectivity inhibited glucocorticoid mediated glucose production may have therapeutic utility in this indication (J.E. Freidman et al., J. Biol. Chem., 1997, 272, pp. 31475-31481).
Novel ligands for the glucocorticoid receptor have been described in the scientific and patent literature. For example, PCT International Publication No. WO 04/093805 discloses selective spirocyclic glucocorticoid receptor modulators potentially useful in treating many inflammatory diseases, including rheumatoid arthritis and Crohn's disease. PCT International Publication No. WO 04/026248 discloses octahydro-2H-naphtho[l,2-/jindole-4-carboxamide derivatives as selective glucocorticoid receptor modulators potentially useful in treating for the treatment of many inflammatory diseases, including rheumatoid arthritis and Crohn's disease. PCT International Publication No. WO 04/075840 discloses selective non-steroidal glucocorticoid receptor modulator with potential use as anti-inflammatory agents possessing advantages over the glucocorticoid ligands with respect to side-effects, efficacy, and toxicity. PCT International Publication No. WO 03/086294 discloses lH-benzo[/]indazol-5-yl derivatives as selective glucocorticoid receptor modulators potentially useful in treating for the treatment of many inflammatory diseases, including rheumatoid arthritis and Crohn's disease. PCT International Publication No. WO 03/061651 and the corresponding U.S. Application Publication No. 2005/0054700 disclose non-steroidal ligands for the glucocorticoid receptor, potentially useful in treating metabolic and inflammatory diseases. PCT International Publication No. WO 99/33786 discloses triphenylpropanamide compounds with potential use in treating inflammatory diseases. PCT International Publication No. WO 00/66522 describes nonsteroidal compounds as selective modulators of the glucocorticoid receptor potentially useful in treating metabolic and inflammatory diseases. PCT International Publication No. WO 99/41256 describes tetracyclic modulators of the glucocorticoid receptor potentially useful in treating immune, autoimmune, and inflammatory diseases. U.S. Patent No. 5,688,810 describes various non-steroidal compounds as modulators of glucocorticoid and other steroid receptors. PCT International Publication No. WO 99/63976 describes a non-steroidal, liver- selective glucocorticoid antagonist potentially useful in the treatment of diabetes. PCT International Publication No. WO 00/32584 discloses non-steroidal compounds having anti- inflammatory activity with dissociation between anti-inflammatory and metabolic effects. PCT International Publication No. WO 98/54159 describes non-steroidal cyclically substituted acylanilides with mixed gestagen and androgen activity. U.S. Patent No. 4,880,839 describes acylanilides having progestational activity and EP 253503 discloses acylanilides with antiandrogenic properties. PCT International Publication No. WO 97/27852 describes amides that are inhibitors of farnesyl-protein transferase.
2,2,2-Trifluoro-l,l-bis-[l-(l-propylbutyl)-lH-indol-5-yl]ethanol has been reported as a byproduct of the condensation of 5-bromo-l-(l-propylbutyl)-lH-indole and trifluoroacetyl anhydride under metal halogen exchange conditions (Η. Takami et oL, Ηeterocycles, 1999, 5J_, pp. 1119-1124). The 4,4,4-trifluoro-3-hydroxy-3-[l-(l-propylbutyl)-lH-indol-5-yl]butyric acid ethyl ester has been disclosed as a product of a Reformatsky reaction between bromoacetic acid ethyl ester and 2,2,2-trifluoro-l-[l-(l-propylbutyl)-lH-indol-5-yl]ethanone (Η. Takami et al., Med. Chem. Res. EN, 1999, 9(4), pp. 239-248).
A compound that is found to interact with the glucocorticoid receptor in a binding assay could be an agonist or an antagonist. The agonist properties of the compound could be evaluated in the transactivation or transrepression assays described above. Given the efficacy demonstrated by available glucocorticoid drugs in inflammatory and immune diseases and their adverse side effects, there remains a need for novel glucocorticoid receptor agonists with selectivity over other members of the steroid receptor family and a dissociation of the transactivation and transrepression activities. Alternatively, the compound may be found to have antagonist activity. As mentioned above, glucocorticoids stimulate glucose production in the liver. Increased glucose production induced by glucocorticoid excess can exacerbate existing diabetes or trigger latent diabetes. Thus, a ligand for the glucocorticoid receptor that is found to be an antagonist may be useful, inter alia, for treating or preventing diabetes.
Summary of the Invention
The instant invention is directed to compounds of Formula (IA)
Figure imgf000007_0001
wherein:
R1 is aryl, heteroaryl, or C3-C7 cycloalkyl each optionally independently substituted with one to three substituent groups selected from Ci-C3 alkyl, hydroxy, halogen, oxo, methoxy, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a methyl group; or thiomethyl wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;
R2 is hydrogen or a halogen;
A and B are each independently CH or N;
C and E are each independently a bond or a -CH2-;
D is -CR4R5-, where R4 is -CF3 and R5 is -OH; and is C1 -Cβ alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, NR6R7, OR8, or SR9, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently aryl, heteroaryl, heterocyclyl, C1-C5 alkyl, Cj-C5 alkenyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C5 alkanoyloxy, Ci-C5 alkanoyl, aroyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, Ci-C5 alkylaminocarbonyloxy, Ci-C5 dialkylaminocarbonyloxy, Cj-C5 alkanoylamino, Ci-C5 alkoxycarbonylamino, Ci-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, CpC5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, carboxyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from aryl, heteroaryl, heterocyclyl, acyl, Cj-C5 alkyl, Ci-C5 alkanoyloxy, Cj-C5 alkanoyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, Ci-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Cj-C5 dialkylaminosulfonyl, Cj-C5 alkyloxy, Cj-C5 cycloalkyl, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Cj-C5 alkyl, or Cj-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or C1-C3 alkyl, and
R7, R8, and R9 are each independently Ci-C5 alkyl, CpC5 alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl optionally independently substituted with one to three substituent groups,
wherein each substituent group of R7, R8, and R9 is independently heteroaryl, heterocyclyl, Ci-C5 alkyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C5 alkanoyloxy, Ci-C5 alkanoyl, aroyl, C1-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C1-C5 alkylaminocarbonyloxy, C1-C5 dialkylaminocarbonyloxy, C1-Cs alkanoylamino, C1-C5 alkoxycarbonylamino, C1- C5 alkylsulfonylatnino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, C1-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Cj-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R7, R8, and R9 is optionally independently substituted with one to three substituent groups selected from heteroaryl, heterocyclyl, acyl, Ci-C5 alkyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, C1-C5 alkylsulfonylamino, aminosulfonyl, CpC5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, C1-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
One aspect of the invention includes compounds of Formula (IA), wherein:
R1 is aryl or heteroaryl optionally independently substituted with one to three substituent groups selected from hydroxy, halogen, or oxo;
R2 is hydrogen; and
C is a bond and E is a bond or -CH2-,
or a tautomer, prodrug, solvate, or salt thereof. One aspect of the invention includes compounds of Formula (IA), wherein:
R1 is a phenyl optionally substituted with one to three halogen groups;
A is N;
B is CH; and
R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1 ,2,3,4-tetrahydroisoquinoline, N-ethyl-iV -methylbenzene- 1 ,2-diamine,
1,2,3,4-tetrahydroquinoline, NR6R7, OR8, or SR9 group, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently C1-Cs alkyl, heteroaryl, heterocyclyl, acyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, C1-Cs alkenyl, carboxyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C1-Cs alkyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or a methyl group, and
R7, R8, and R9 are each independently a phenyl, naphthyl, pyridyl, pyrimidyl, quinoline, isoquinoline, or indolyl optionally independently substituted with one to three substituent groups, wherein each substituent group of R7, R8, and R9 is independently heterocyclyl, Ci-C5 alkyl, cycloalkyl, acyl, Ci-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
One aspect of the above embodiment includes compounds of Formula (IA), wherein:
R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1,2,3,4-tetrahydroisoquinoline, N-ethyl-N'-methylbenzene-l,2-diamine, or 1 ,2,3 ,4-tetrahydroquinoline,
. wherein each substituent group of R3 is independently Cj-C5 alkyl, C1-C5 alkenyl, carboxyl, acyl, Ci-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from CpC5 alkyl, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
Representative compounds of Formula (IA) according to the invention are appended hereto as Table IA, where column A is the compound name according to standard nomenclature and column B is the corresponding chemical structure. Preferred compounds of Formula (IA) include the following:
1 -Biphenyl-3-yl-2,2,2-trifluoro- 1 -(I -phenyl-lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3,5-Difluorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(3 -Chloro-5-fluorophenyl)-2,2,2-trifluoiO- 1 -(I -phenyl- 1 H-indazol-5 -yl)ethanol;
l-(4-Chloro-3-methylphenyl)-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chlorophenyl)-2,2,2-tπfluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(4-ChloiO-3-fluoiOphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3,5-DichloiOphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-fluorophenyl)- 1 -( 1 -phenyl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-methylnaphthalen-l-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluorophenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(2,2-Difluoro- 1 ,3 -benzodioxol-4-yl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,2-Difluoro- 1 ,3-benzodioxol-4-yl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(4-Chlorophenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -phenyl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -(2,4,5-trimethylphenyl)ethanol;
2,2,2-Trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)- 1 -(2,4,6-trimethylphenyl)ethanol;
l-(4-fert-Butyl-2,6-dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-methoxyphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol;
1 -(3,5-Dimethylphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-methoxy-3,5-dimethylphenyl)-l -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3,4-Dimethylphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-fluoro-4-methoxyphenyl)- 1 -( 1 -phenyl- 1 H- indazol-5-yl)ethanol; 2,2,2-TrifluoiO-l -(5-fluoro-2-methoxyphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,5-Dimethoxyphenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-morpholin-4-ylmethylphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
1 -Biphenyl-2-yl-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoiO-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
1 -(4-Dimethylaminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methylnaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxynaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-naphthalen-2-yl-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(l-phenyl-lH-indazol-5-yl)-l-quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 -(I H-indol-4-yl)- 1 -( 1 -phenyl- lH-indazol-5 -yl)ethanol;
1,1,1 -Trifluoro-3 -indol- 1 -yl-2-( 1 -phenyl- lH-indazol-5 -yl)propan-2-ol;
1 -[3,3,3-Trifluoro-2-hydroxy-2-(l -phenyl- lH-indazol-5-yl)propyl]- lH-indole-3-carbonitrile;
3-(3 ,4-Dihydro-2H-quinoxalin-l -yl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(3,4-Dihydro-2H-quinolin- 1 -yl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-3-(3-fluoiOphenyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-phenyl-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1 , l-Trifluoro-2-phenyl-3-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-phenylsulfanylpropan-2-ol;
l,l,l-Trifluoro-3-(4-fluorophenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-phenoxy-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(3 ,5-Difluorophenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(3,5-Dimethoxyphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l-Benzo[&]thiophen-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(l-phenyl-lH-indazol-5-yl)-l-quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 -isoquinolin- 1 -yl- 1 -(I -phenyl- IH- indazol-5-yl)ethanol;
l-Benzo[&]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -naphthalen- 1 -ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]ethanol; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(4-methylnaphthalen-l-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-4-yl)ethanol;
l-Benzo[δ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoiO-l-[l-(4-fluoiOphenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -phenyl- 1 H-benzotriazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(6-fluoropyridin-2-yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
3 -(3-Chloro-2-fluorophenyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-fluorophenyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-2-fluorophenyl)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-7-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-7-yl)ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-l -(I -methyl- lH-indol-5-yl)ethanol; 2,2,2-Tπfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-6-yl)ethanol;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indole-l-carboxylic acid iert-butyl ester;
1 -(3-Aminophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
N-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenyl}acetamide;
1 -Methyl-4- {2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- quinolin-2-one;
l-(l-Allyl-lH-indol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
3-(4-{2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} indol- 1 - yl)propane- 1 ,2-diol;
3-Hydroxy-4-(4-{2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol- 1 -yl)butyronitrile;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -[I -(2-hydroxyethyl)- lH-indol-4- yl]ethanol;
2-(4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)acetamide;
N-Methyl-2-(4-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} indol- l-yl)acetamide;
1 -[ 1 -(2-Cyclopropyl-2-hydroxyethyl)- 1 H-indol-4-yl]-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]ethanol; 1 -(7-Bromo- 1 -methyl- 1 H-indol-3 -yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
1 -Methyl-3-{2,2,2-trifluoiO- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid methyl ester;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methylamide;
1 -Methyl-3-{2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid (2-cyanoethyl)amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)amide;
1 -Methyl-3-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} -IH- indole-7-carboxylic acid (2-methoxyethyl)methylamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-7-nitro-lH-indol-3- yl)ethanol;
l-(7-Amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid carbamoylmethylamide; l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid cyanomethylamide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
N-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indol-7-yl)methanesulfonamide;
3-(3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydiOxyethyl}indol-l- yl)propane- 1 ,2-diol;
l-Benzyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
2-(3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydiOxyethyl}indol-l- yl)acetamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol-3- yl]ethanol;
N-Methyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol- l-yl)acetamide;
N-Cyanomethyl-2-(3-{2,2,2-tπfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Carbamoylmethyl-2-(3 - {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 - hydiOxyethyl}indol-l-yl)acetamide;
l-Morpholin-4-yl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)ethanone; l-Allyl-3-{2,2,2-trifluoiO-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydiOxyethyl}-lH-indole- 7-carboxylic acid methyl ester;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole- 7-carboxylic acid amide;
l-(2,3-Dihydroxypropyl)-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}-lH-indole-7-carboxylic acid amide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
3- {3-[2,2,2-Trifluoro- 1 -hydroxy- 1 -(I -p-tolyl- lH-indazol-5-yl)ethyl]indol- 1 -yl}propane- 1 ,2- diol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -phenyl- lH-indol-5-yl)ethanol;
1 -(3,4-Dichlorophenyl)-2,2,2-trifluoro- 1 -(I -pyridin-2-yl- lH-indazol-5-yl)ethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -(I -pyridin-2-yl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol;
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]ethanol; 2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -p-tolyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-methoxyphenyl)- lH-indazol-5-yl]- 1 -phenylethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -(I -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -o-tolyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(2-fluoroρhenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -(5-fluoro-lH-indol-3-yl)- 1 -[ 1 -(4-methoxyphenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
3-[2,2,2-Trifluoro- 1 -hydroxy- 1 -(I -phenyl- lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro- 1 -(4-fluoro-3-hydroxymethylphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(5-methoxy-4-methyl-lH-indol-3- yl)ethanol;
l-(4-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(6-methoxy- 1 H-indol-3-yl)ethanol; l-(2,5-Dimethyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(7-methoxy- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-(lH-indol-3-yl)ethanol;
l-(6-Brorao-lH-indol-3-yl)-2,2,2-tπfluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol;
l-(7-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol;
l-(5-Bromo-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methyl-lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(2-methyl-lH-indol-3-yl)ethanol;
l-(6-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(5-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(4-Bromo-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(4-fluoro-lH-indol-3-yl)~l -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(6-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(5-methoxy-lH-indol-3-yl)ethanol;
2,2,2-Trifluoro- 1 -(7-fluoro- lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol; 2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methyl-lH-indol-3-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(7-methyl-lH-indol-3-yl)ethanol;
3- {2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- lH-indole-5- carbonitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-3-yl)ethanol;
1 -(6-Bromo- 1 -methyl- 1 H-indol-3 -yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-6-carbonitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-3-yl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-4-yl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-morpholin-4-yl-lH- indol-3-yl)ethanol;
1 -Methyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} -IH- indole-6-carboxylic acid methyl ester;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-furan-2-yl-l-methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-β-pyrimidin-S-yl- IH- indol-3-yl)ethanol; 2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -{6-[(2-methoxyethyl)methylamino]- 1 -methyl- lH-indol-3-yl}ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -[6-(2-methoxyethylamino)- 1 -methyl- lH-indol-3-yl]ethanol;
1 -{6-[(2-Dimethylaminoethyl)methylamino]- 1 -methyl- lH-indol-3-yl} -2,2,2-trifluoro- 1 -[ 1 -(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-5-morpholin-4-yl- IH- indol-3 -yl)ethanol ;
l-[6-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -[5-(2-Dimethylaminoethylamino)- 1 -methyl- lH-indol-3-yl]-2,2,2-trifluoro- 1-[1 -(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrrolidin-l-yl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-(l-methyl-5-pyrrolidin-l-yl-lH- indol-3 -yl)ethanol ;
1 -[6-Bromo- 1 -(4-methoxybenzyl)- 1 H-indol-3 -yl]-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]ethanol;
N-Carbamoylmethyl-N-methyl-2-{3-[2,2,2-trifluoro- 1 -hydroxy- 1 -(I -p-tolyl-lH-indazol-5- yl)ethyl]indol-l-yl}acetamide; N-Carbamoylmethyl-2-{3-[2,2,2-trifluoro-l-hydiOxy-l-(l-i?-tolyl-lH-indazol-5-yl)ethyl]indol- l-yl}acetamide;
N-(2-Methoxyethyl)-N-methyl-2-{3-[2,2,2-trifluoiO- 1 -hydroxy- 1 -(I -p-tolyl- lH-indazol-5- yl)ethyl] indol- 1 -yl} acetamide;
N-(2-Methoxyethyl)-2- { 3 -[2,2,2-trifluoro- 1 -hydroxy- 1 -(I -p-tolyl- 1 H-indazol-5-yl)ethyl] indol- l-yl}acetamide;
N-Cyanomethyl-2- { 3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5 -yl)ethyl] indol- 1 - yl}acetamide;
N-Methyl-2-{3-[2,2,2-trifluoro- 1 -hydroxy- 1 -(I -p-tolyl- lH-indazol-5-yl)ethyl]indol- 1 - yl} acetamide;
2-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-p-tolyl-lH-indazol-5-yl)ethyl]indol-l-yl}acetamide;
2,2,2-Trifluoro-l -[I -(2-hydroxyethyl)- lH-indol-3-yl]- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethanol;
3-{3-[2,2,2-Trifluoro- 1 -hydroxy-1 -( 1 -p-tolyl-lH-indazol-5-yl)ethyl]indol- 1 -yl}propane- 1 ,2- diol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2-trifluoromethylphenoxy)propan-2-ol;
3-(2-Chloro-3,5-difluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(5-Chloro-2-methylphenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(indan-5-yloxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; 1 , 1 ,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trichlorophenoxy)ptOpan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol;
3-(3-Bromophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2-Bromophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenoxy)piOpan-2-ol;
3-(2-Chloro-5-methylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4-trifluoromethylphenoxy)propan-2-ol;
1,1,1 -TrifluoiO-3-(naphthalen-2-yloxy)-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(2-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Chlorophenoxy)- 1 , 1 , l-trifluoro-2-( 1 -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(4-Chloro-2-fluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -TrifluoiO-3-(4-fluoro-2-methylphenoxy)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,3,4-trifluorophenoxy)propan-2-ol;
3-(2-Chloro-3,5-difluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; l,l,l-TrifluoiO-3-(7-methoxynaphthalen-2-yloxy)-2-(l-phenyl-lH-iiidazol-5-yl)piOpan-2-ol;
3-(2-Bromo-5-fluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(2-fluoro-5-trifluoromethylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol;
3-(4-Bromo-3-methylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-TrifluoiO-3-(2-fluoro-5-methylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-methylsulfanylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)- 1 , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenoxy)- 1,1,1 -trifluoro-2~( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-o-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol~5-yl)-3-/«-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-/?-tolyloxypropan-2-ol;
3-(2,6-Dimethylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenoxy)- 1, 1 , 1 ~trifluoro-2-( I -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(naphthalen-l-yloxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(isoquinolin-7-yloxy)-2-(l-phenyl-lH-mdazo{-5-yl)propan-2-o{; l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2-trifluoromethoxyphenoxy)piOpan-2-ol;
1,1,1 -Trifluoro-3 -(4-phenylaminophenoxy)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(3-Chloro-4-methylphenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluoro-5-trifluoromethylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
1,1,1 -Trifluoro-3-(2-methylsulfanylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-Methoxy-4-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propoxy]benzoic acid ethyl ester;
1,1,1 -Trifluoro-3-(4-imidazol- 1 -ylphenoxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazo 1-5- yl)propan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 - yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen-2- yloxy)propan-2-ol; 2-{3,3,3-TrifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile;
3-(2-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2,4-Dichlorophenoxy)- 1 , 1 , 1 -trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6-trichlorophenoxy)propan-2-ol;
3-(2-Chloro-5-methylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan- 2-ol;
3-(2,6-Dichlorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl] -3 -(2 ~trifluoromethylphenoxy)propan-2- ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]-3-σ-tolyloxypropan~2-ol;
3-(2,4-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(2,4,6-trimethylphenoxy)propan-2-ol;
3-(2,6-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile;
3-(3-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluorophenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol; 3-(3,5-DifluoiOphenoxy)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(3-Chlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(3,5-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-m-tolyloxypropan-2-ol;
3-(3,5-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]piOpan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitπle;
3-(4-Bromophenoxy)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 ~Trifluoro-3-(4-fluorophenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(4-Chlorophenoxy)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-trifluoromethylphenoxy)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-p-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(indan-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen-l -yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen-2-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-5-yloxy)propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-8-yloxy)propan-2-ol;
3-(2,4-DifluoiOphenoxy)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(quinolin-7-yloxy)propan-2-ol;
3-Methoxy-4-{3,3,3-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy} benzoic acid ethyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-phenylaminophenoxy)propan-2-ol;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}phenyl)butyramide;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- trifluoromethylsulfanylphenoxy)propan-2-ol;
5-Acetyl-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropoxy}benzoic acid methyl ester;
3-(2-Bromo-5-fluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2~ ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,4-trifluorophenoxy)propan-2-ol;
3-(2,5-Difluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(4-Chloro-3-trifluoromethylphenoxy)- 1 , 1 , l-trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(Acridin-4-yloxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3-morpholin-4-ylphenoxy)propan-2- ol;
2-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(4-Bromo-2-methylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-(3-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-(5-Chloro-2-methylphenoxy)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol~5-yl]propan- 2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,6-trifluorophenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,5-trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6-trifluorophenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-fluoro-5- trifluororaethylphenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan- 2-ol;
3-(4-Chloro-2-fluoroρhenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]proρan-2- ol; 1,1,1 -Trifluoro-3 ~(4-fluoro-2~methylphenoxy)-2-[ 1 -(4-fluorophenyl)- 1 H~indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-3-(2-fluoiO-6-methoxyphenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-(2-Chloro-3,5-difluoiOphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,5-trifluorophenoxy)propan-2-ol;
4- { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropoxy } benzonitrile ;
3-(4-Bromo-3-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxynaphthalen-2- yloxy)propan-2-ol;
3 -(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazo 1-5- yl]propan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}indan-l-one;
5-Bromo-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
1,1,1 -Trifluoro-3-(2-fluoro-5-methylphenoxy)-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan- 2-ol; 5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2- hydroxypropoxy } benzonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-trifluoiOmethoxyphenoxy)propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(isoquinolin-7-yloxy)propan-2-ol;
3-(3,4-Dimethoxyphenoxy)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(3-trifluoromethoxyphenoxy)piOpan- 2-ol;
3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3 -(2-isopropylphenylsulfanyl)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
3-(4-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
4-Methyl-7-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-l- benzopyran-2-one;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(3 -trifluoromethylphenylsulfanyl)propan-2-ol;
3-(2,3-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3 -(naphthalen- l-ylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-thiophen-2-ylpyrimidin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-phenylpyrimidin-2-ylsulfanyl)propan-2-ol;
3-[4-(4-Chlorophenyl)pyrimidin-2-ylsulfanyl]- 1 ,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5- yl)proρan-2-ol;
6-Methyl-2-[3,3,3-trifluoro-2-hydiOxy-2-(l-phenyl-lH-indazol-5-yl)piOpylsulfanyl]-4- trifluoromethylnicotinonitrile;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(5-trifluoromethylpyridin-2-ylsulfanyl)propan- 2-ol;
3-(2-Chloro-4-fluorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)-3 -(4-trifluoromethoxyphenylsulfanyl)propan-2- ol;
3-(4-Bromo-2-trifluoiOmethoxyphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5- yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-methoxyphenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)-3-(quinolin-2-ylsulfanyl)propan-2-ol;
3-(4-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(pyπmidin-2-ylsulfanyl)propan-2-ol; 3-(4,6-Dlmethylpyrimidin-2-ylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3-(3,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(pyridin-4-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-methoxyphenylsulfanyl)-2-( 1-phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-methoxyphenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(3-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(3 -Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5 -yl)propan-2-ol;
3-(3 ,4-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(naphthalen-2-ylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluorophenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(2,5-Dimethoxyphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; 3-(2,5-Dimethylphenylsulfanyl)- 1,1,1 -trlfluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2-Ethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
2-[3,3,3-Trifluoro-2-hydiOxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]benzoic acid methyl ester;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3 -(4-trifluoiOmethylpyrimidin-2- ylsulfanyl)propan-2-ol;
3 -(3 ,5-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(3 , 5 -Bis-trifluoromethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3-(2,4-DifluoiOphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoiO-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3 ,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- IH- indazol-5-yl)-3-(2-trifluoromethylphenylsulfanyl)propan-2-ol;
3-(3,4-Difluorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Ethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol; 3-(4-ferM3utylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propylsulfanyl]phenyl } acetamide;
3-(4-Bromophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(2-isopropylphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Tri£luoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
1,1,1 -TrifluoiO-3-(4-nitrophenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-o-tolylsulfanylpropan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-w-tolylsulfanylpropan-2-ol;
1,1,1 -TrifluoiO-2-(l -phenyl- IH- indazol-5-yl)-3-/>tolylsulfanylpropan-2-ol;
3-(3-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,4-Dimethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(5-fert-Butyl-2-methylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)-3-(2,4,6-trimethylphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l-phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan-2-ol; 1,1,1 -Trifluoro-3-(4-methylsulfanylphenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(2-Chloro-6-methylphenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(2-tørM3utylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylpyπdin-2-ylsulfanyl)piOpan- 2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethoxyphenylsulfanyl)propan-2- ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-methylindol- 1 -yl)propan-2-ol;
3-[2-(4-Chlorophenyl)indol- 1 -yl]-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)acetonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxyindol- 1 -yl)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(5-methylindol-l-yl)propan-2-ol;
3-(4-Benzyloxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(4-Chloroindol- 1 -yl)- 1 , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(6-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methylindol- 1 -yl)propan-2-ol; l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-4- carboxylic acid methyl ester;
1,1,1 -TrifluoiO-3-(6-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxyproρyl}-lH-indole-3- carboxylic acid methyl ester;
2,2,2-Trifluoro-l-(l-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2- hydroxypropyl}-lH-indol-3-yl)ethanone;
1,1,1 -Trifluoro-3-(4-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
N-[2-(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}- lH-indol-3-yl)ethyl]acetamide;
3-(7-Bromoindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol;
3-(7-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
(2-Methyl- 1 - { 3 ,3 ,3 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-2-hydroxypropyl } - IH- indol-3-yl)acetic acid ethyl ester;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-5- carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methyl-5-nitroindol- 1 -yl)propan- 2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-[2-(4-fluorophenyl)indol- 1 - yl]propan-2-ol; 3-(4-Bromoindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]piOpan-2-ol;
3-(6-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(3 -Dimethylaminomethyl-6-methoxyindol- 1 -yl)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]propan-2-ol;
(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}-lH- indol-3-yl)acetonitrile;
(5 -B enzyloxy- 1 - { 3 ,3 ,3 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H- indol-3 -yl)acetonitrile ;
l-{3,3,3-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-6- carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(7-nitroindol- 1 -yl)propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-4- carbonitrile;
3-(5-Benzyloxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l-(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-5- carbonitrile;
3-(3-Dimethylaminomethyl-5-methoxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH- indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-3-(5-methoxy-2-methylindol- 1 - yl)propan-2-ol; l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methylindol-l-yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(3-methylindol- 1 -yl)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-methylindol-l-yl)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-nitroindol-l-yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-phenylindol- 1 -yl)propan-2-ol;
(2-Phenyl-l-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydiOxypiOpyl}-lH- indol-3-yl)acetonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-pyrrolo[2,3-c]pyridin- 1 -ylpropan-2- ol;
3-(7-Ethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2,3-Dimethyl-5-nitroindol-l -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(6-trifluoromethylindol- 1 -yl)propan- 2-ol;
1,1,1 -Trifluoro-3-(7-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indole-6- carbonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-indol- 1 -ylpropan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-pyrrolo[2,3-δ]pyridin-l-ylpropan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-2- carboxylic acid ethyl ester;
3 -(2,3-Dimethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1 - {3,3,3-Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-2-hydroxypropyl}- lH-indole-3- carbonitrile;
l-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)ethanone;
3-(3-Dimethylaminomethylindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(3-Dimethylaminomethyl-5-methoxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH- indazol-5-yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)acetic acid ethyl ester;
2-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)acetamide;
3-(5-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3 -(5-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol;
3-(5-Chloroindol-l-yl)-l,l,l-trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-methoxyindol-l-yl)propan-2-ol; 3-(5,6-Dimethoxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]piOpan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(4-nitroindol-l-yl)propan-2-ol; and
5-Methyl-l-{3,3,3-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypiOpyl}-lH- indole-2-carboxylic acid ethyl ester,
or a tautomer, prodrug, solvate, or salt thereof.
More preferred compounds of Formula (IA) include the following:
1 -Biphenyl-3-yl-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3,5-DifluoiOphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
l-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-methylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3 -fluorophenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro- 1 -(4-methylnaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-CS^-DichlorophenyO^^^-tπfluoro-l-Cl-phenyl-lH-indazol-S-yOethanol;
2,2,2-Trifluoro- 1 -(4-fluorophenyl)- 1 -(I -phenyl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-fluoro-4-methylplienyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-methoxyphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-TrifluoiO-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphtlialen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(4-Dimethylaminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxynaphthalen- 1 -yl)- 1 -(I -phenyl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro-l-(lH-indol-4-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l,l,l-Trifluoro-3-(3-fluorophenyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-3-phenyl-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,5-Difluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl-lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 -isoquinolin- 1 -yl- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
l-Benzo[δ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -phenylethanol;
l-(3-Chloro-4-fluoiOphenyl)-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -naphthalen- 1 -ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(4-methylnaphthalen-l -yl)ethanol;
1 -Benzo [&]thiophen-3 -yl-2,2,2-trifluoro- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -(2,2-Difluoro- 1 ,3-benzodioxol-4-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -(6-fluoropyridin-2-yl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol; 3 -(3 -Chloro-2-fluorophenyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-fluorophenyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(4-ChloiO-2-fluorophenyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
l-(2,2-DifluoiO-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-7-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-7-yl)ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl- lH-indol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl- lH-indol-6-yl)ethanol;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indole-l-carboxylic acid tert-butyl ester;
l-(3-Aminophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
N- { 3 -[2,2,2-Trifluoro- 1 -hydroxy- 1 -(I -phenyl- IH- indazol-5-yl)ethyl]phenyl } acetamide;
1 -Methyl-4- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} - 1 H- quinolin-2-one;
1 -( 1 -Allyl- 1 H-indol-4-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- 1 H-indazol-5-yl]ethanol; 3-(4-{2,2,2-Trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -hydroxyethyl} indol- 1 - yl)propane- 1 ,2-diol;
3 -Ηydroxy-4-(4- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxyethyl } indol- l-yl)butyronitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol-4- yljethanol;
2-(4- {2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxyethyl} indol- 1 - yl)acetamide;
N-Methyl-2-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol- l-yl)acetamide;
l-[l-(2-Cyclopropyl-2-hydroxyethyl)-lH-indol-4-yl]-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]ethanol;
l-(7-Bromo-l-methyl-lH-mdol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
1 -Methyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl] - 1 -hydroxyethyl } - IH- indole-7-carboxylic acid methyl ester;
1 -Methyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
1 -Methyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxyethyl } - IH- indole-7-carboxylic acid methylamide; 1 -Methyl-3-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid (2-cyanoethyl)amide;
l-Methyl-3-{2,2,2-trifluoiO-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)amide;
1 -Methyl-3-{2,2,2-trifluoro-l -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} - IH- indole-7-carboxylic acid (2-methoxyethyl)methylamide;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -(I -methyl-7-nitro- lH-indol-3 - yl)ethanol;
l-(7-Amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid carbamoylmethylamide;
1 -Methyl-3-{2,2,2-trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid cyanomethylamide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
N-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indol-7-yl)methanesulfonamide;
3-(3-{2,2,2-Trifluoro- 1 -[l-(4-fluoropheiiyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} indol- 1 - yl)propane- 1 ,2-diol;
l-Benzyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester; 2-(3-{2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} indol- 1 - yl)acetamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydiOxyethyl)-lH-indol-3- yl]ethanol;
N-Methyl-2-(3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl } indol- l-yl)acetamide;
N-Cyanomethyl-2-(3-{2,2,2-tπfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Carbamoylmethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl} indol- 1 -yl)acetamide;
l-Morpholin-4-yl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)ethanone ;
1 -Allyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -hydroxyethyl}- lH-indole- 7-carboxylic acid methyl ester;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole- 7-carboxylic acid amide;
l-(2,3-Dihydroxypropyl)-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}-lH-indole-7-carboxylic acid amide;
l-Cl-Allyl-lH-indol-S-yO^^^-trifluoro-l-Cl-p-tolyl-lH-indazol-S-y^ethanol;
3- { 3 -[2,2,2-Trifluoro- 1 -hydroxy- 1 -(I -p-tolyl- 1 H-indazol-5-yl)ethyl] indol- 1 -yl }propane- 1 ,2- diol; ,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)-l -(I -phenyl- lH-indol-5 -yl)ethanol;
2,2,2-Trifluoro-l-naphthalen-l-yl-l-(l-phenyl-lH-indol-5-yl)ethanol;
l-CS^-DichlorophenyO^^^-trifluoro-l-Cl-pyridin^-yl-lH-indazol-S-yOethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
l-CS^-DifluorophenyO^^^-trifluoro-l-Cl-pyridin^-yl-lH-indazol-S-yOethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -(I -pyridin-2-yl- lH-indazol-5-yl)ethanόl;
2,2,2-Trifluoro- 1 -[I -(2-fluorophenyl)- lH-indazol-5-yl]- 1 -phenylethanol;
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[I -(2-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-methoxyphenyl)-lH-indazol-5-yl]-l-phenylethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-o-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)-l -(I -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-TrifluoiO-l-(5-fluoro-lH-indol-3-yl)-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(2-fluoiOphenyl)-lH-indazol-5-yl]ethanol; 2,2,2-Trifluoro-l-(5-fluoiO-lH-indol-3-yl)-l-[l-(4-methoxyphenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-TrifluoiO-l-(4-fluoro-3-hydroxymethylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
4-[2,2,2-TrifluoiO-l -hydroxy- 1 -(I -phenyl- lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(5-methoxy-4-methyl-lH-indol-3- yl)ethanol;
l-(4-Chloro-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(6-methoxy- lH-indol-3-yl)ethanol;
l-(2,5-Dimethyl-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(7-methoxy- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-3-yl)ethanol;
l-(6-Bromo-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -(7-Bromo- lH-indol-3 -yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]ethanol;
1 -(5-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methyl-lH-indol-3-yl)ethanol; 2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(2-methyl-lH-indol-3-yl)ethanol;
1 -(6-Chloro- 1 H-indol-3-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
l-(5-Chloro-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -(4-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoiO-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -(4-fluoro- lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(6-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(5-methoxy- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-(7-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(6-methyl- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methyl-lH-indol-3-yl)ethanol;
3-{2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole-5- carbonitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-3-yl)ethanol;
l-(6-Bromo-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5- yljethanol;
1 -Methyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxyethyl } - 1 H- indole-6-carbonitrile; 2,2,2-Tπfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-3-yl-lH-indol-3- yl)ethanol;
2,2,2-Tπfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-4-yl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(I -methyl-β-morpholin^-yl- IH- indol-3 -yl)ethanol;
1 -Methyl-3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-l -hydiOxyethyl}-lH- indole-6-carboxylic acid methyl ester;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(6-furan-2-yl- 1 -methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -( 1 -methyl-6-pyrimidin-5-yl- IH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-{6-[(2-methoxyethyl)methylamino]- l-methyl-lH-indol-3-yl}ethanol;
2,2,2-Trifluoro- 1-[1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -[6-(2-methoxyethylamino)- 1 -methyl- 1 H-indol-3 -yl] ethanol ;
1 -{ 6-[(2-Dimethylaminoethyl)methylamino]- 1 -methyl- 1 H-indol-3-yl} -2,2,2-trifluoro- 1 -[ 1 -(4- fluorophenyl)- 1 H-indazol-5 -yl] ethanol ;
2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-5-morpholin-4-yl-lH- indol-3-yl)ethanol; l-[6-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-tπfluoro-l-[l-(4- fluoropheny I)- 1 H-indazol-5 -yl] ethanol ;
l-[5-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl] - 1 -( 1 -methyl-6-pyrrolidin- 1 -yl- IH- indol-3-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-5-pyrrolidin- 1 -yl- IH- indol-3-yl)ethanol;
1 -[6-Bromo- 1 -(4-methoxybenzyl)- lH-indol-3-yl]-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- IH- indazol-5-yl]ethanol;
N-Carbamoylmethyl-N-methyl-2-{3-[2,2,2-trifluoro- 1 -hydroxy- 1 -(I -p-tolyl- lH-indazol-5- yl)ethyl]indol- 1 -yl}acetamide;
N-Carbamoylmethyl-2- { 3 -[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethyl] indol- l-yl}acetamide;
Ν-(2-Methoxyethyl)-N-methyl-2- {3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- 1 H-indazol-5 - yl)ethyl]indol- 1 -yl } acetamide;
Ν-(2-Methoxyethyl)-2-{3-[2,2,2-trifluoro-l-hydiOxy-l-(l-p-tolyl-lH-indazol-5-yl)ethyl]indol- 1-yl} acetamide;
N-Cyanomethyl-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-/>-tolyl-lH-indazol-5-yl)ethyl]indol-l- yl} acetamide;
N-Methyl-2-{3-[2,2,2-trifluoro- 1 -hydroxy-1 -( 1 -p-tolyl- lH-indazol-5-yl)ethyl]indol- 1 - yl}acetamide; 2-{3-[2,2,2-TrifluoiO-l-hydroxy-l-(l-/?-tolyl-lH-indazol-5-yl)ethyl]indol-l-yl}acetamide;
2,2,2-TrifluoiO-l-[l-(2-hydroxyethyl)-lH-indol-3-yl]-l-(l-^-tolyl-lH-indazol-5-yl)ethanol;
S-IB-P^^-TrifluoiO-l-hydiOxy-l-Cl-p-tolyl-lH-indazol-S-yOetliyllindol-l-yllpropane-l^- diol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2-trifluoromethylphenoxy)propan-2-ol;
3 -(2-Chloro-3 ,5-difluorophenoxy)- 1 , 1 , 1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(5-Chloro-2-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3 -(4-Bromophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- IH- indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3-(indan-5-yloxy)-2-( 1 -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trichlorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol;
3-(3-Bromophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(2-Bromophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenoxy)propan-2-ol;
3-(2-Chloro-5-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylphenoxy)propan~2-ol;
1,1,1 -Trifluoro-3-(naphthalen-2-yloxy)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Chlorophenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(4-Chloro-2-fluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -TrifluoiO-3-(4-fluoro-2-methylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- IH- indazol-5-yl)-3-(2,3,4-trifluorophenoxy)propan-2-ol;
3-(2-Chloro-3,5-difluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(7-methoxynaphthalen-2-yloxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(2-Bromo-5-fluorophenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
l,l,l-Tπfluoro-3-(2-fluoiO-5-trifluoiOmethylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol;
3-(4-Bromo-3-methylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(2-fluoro-5-methylphenoxy)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-methylsulfanylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol; 3-(3-Chlorophenoxy)- 1 , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-o-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3 -»?-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-p-tolyloxypropan-2-ol;
3-(2,6-Dimethylphenoxy)- 1,1,1 -trifluoro-2-(l-phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l-phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(naphthalen- 1 -yloxy)-2-(l-phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3~(isoquinolin-7-yloxy)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
l,l,l-TrifluoiO-2-(l-phenyl-lH-indazol-5-yl)-3-(2-trifluoromethoxyphenoxy)propan-2-ol;
1,1,1 -Trifluoro-3-(4-phenylaminophenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chloro-4-methylphenoxy)- 1 , 1 , l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(3 -fluoro-5 -trifluoromethy lphenoxy)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
1,1,1 -Trifluoro-3 -(2-methylsulfanylphenoxy)-2-( 1 -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-tπfluoromethylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol; 3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichloro-4-methylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-Methoxy-4-[3,3,3-trifluoiO-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)piOpoxy]benzoic acid ethyl ester;
l,l,l-Trifluoro-3-(4-imidazol-l-ylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol;
3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 - yloxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen-2- yloxy)propan-2-ol;
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile;
3-(2-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1 , 1 , 1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6-trichlorophenoxy)propan-2-ol;
3-(2-Chloro-5-methylphenoxy)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol; 3-(2,6-DichloiOphenoxy)-l,l,l-trifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]piOpan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-trifluoromethylphenoxy)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-o-tolyloxypiOpan-2-ol;
3-(2,4-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6-trimethylphenoxy)propan-2-ol;
3-(2,6-Dimethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropoxy}benzonitrile;
3-(3-Bromophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-3-(3-fluorophenoxy)-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(3,5-Difluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(3-Chlorophenoxy)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(3,5-Dichlorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-m-tolyloxypropan-2-ol;
3-(3,5-Dimethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol; 1,1,1 -Trifluoro-3 -(4-fluorophenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3 -(4-Chlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol;
l,l,l-TrifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-tπfluoromethylphenoxy)propan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-p-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(indan-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro~2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen- 1 -yloxy)propan-2-ol;
l,l,l-TπfluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(naphthalen-2-yloxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(quinolin-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-8-yloxy)propan-2-ol;
3-(2,4-Difluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(quinolin-7-yloxy)propan-2-ol;
3-Methoxy-4- { 3 ,3 ,3-trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-2- hydroxypropoxy}benzoic acid ethyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-phenylaminophenoxy)propan-2-ol;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}phenyl)butyramide; 1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- trifluoromethylsulfanylphenoxy)propan-2-ol;
5-Acetyl-2-{3,3,3-trifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzoic acid methyl ester;
3 -(2-Bromo-5-fluoiOphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,4-trifluorophenoxy)propan-2-ol;
3-(2,5-Difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(4-Chloro-3-trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5- yl]propan-2-ol;
3-(Acridin-4-yloxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -y 1] -3 -(3 -morpholin-4-ylphenoxy)propan-2- ol;
2-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy } benzonitrile;
3-(4-Bromo-2-methylphenoxy)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-(3-Chloro-4-methylphenoxy)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-(5-Chloro-2-methylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,6-trifluorophenoxy)piOpan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,5-trifluorophenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6-trifluorophenoxy)propan-2-ol;
1, 1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2~[l -(4-fluorophenyl)- IH- indazol-5-yl]propan- 2-ol;
3-(4-Chloro-2-fluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-3-(4-fluoro-2-methylphenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-6-methoxyphenoxy)-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan- 2-ol;
3-(2-Chloro-3,5-difluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1 ,1 ,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,5-trifluorophenoxy)propan-2-ol;
4- { 3 ,3 ,3-Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-2-hydroxypropoxy } benzonitrile; 3-(4-Bromo-3-methylphenoxy)- 1 , 1 , l-trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxynaphthalen-2- yloxy)propan-2-ol;
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
4- { 3 ,3 ,3 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5-yl]-2-hydroxypropoxy } indan- 1 -one;
5-Bromo-2-{3,3,3-tπfluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
l,l,l-TrifluoiO-3-(2-fluoiO-5-methylphenoxy)-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]piOpan- 2-ol;
5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy } benzonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-trifluoromethoxyphenoxy)propan- 2-ol;
1,1, l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(isoquinolin-7-yloxy)piOpan-2-ol;
3-(3,4-Dimethoxyphenoxy)-l,l,l-tπfluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-trifluoromethoxyphenoxy)propan- 2-ol;
3-(2,4-Dichloro-6-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5- yl]propan-2-ol; 1 , 1 , 1 -Trifluoro-3 -(2-isopropylphenylsulfanyl)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
3-(4-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
4-Methyl-7-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-l- benzopyran-2-one;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan-2-ol;
3-(2,3-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(naphthalen- 1 -ylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-thiophen-2-ylpyrimidin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-phenylpyrimidin-2-ylsulfanyl)propan-2-ol;
3-[4-(4-Chlorophenyl)pyrimidin-2-ylsulfanyl]- 1 ,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol;
6-Methyl-2-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-4- trifluoromethylnicotinonitrile;
l,l,l-TrifluoiO-2-(l-phenyl-lH-indazol-5-yl)-3-(5-trifluoromethylpyridin-2-ylsulfanyl)propan- 2-ol; 3 -(2-ChloiO-4-fluorophenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(4-trifluoromethoxyphenylsulfanyl)propan-2- ol;
3-(4-BiOmo-2-trifluoromethoxyphenylsulfanyl)-l ,1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-methoxyphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(quinolin-2-ylsulfanyl)piOpan-2-ol;
3-(4-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)-3 -(pyrimidin-2-ylsulfanyl)propan-2-ol;
3-(4,6-Dimethylpyrimidin-2-ylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol;
3-(3,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-1 H-indazol-5-yl)propan-2-ol;
3 -(2,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- IH- indazol-5-yl)-3-(pyridin-4-ylsulfanyl)propan-2-ol;
l,l,l-Trifluoro-3-(3-methoxyphenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol;
1,1,1 -Trifluoro-3-(2-methoxyphenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; -(2,6-Dichlorophenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3 -Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(3 ,4-Dimethylphenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol ;
1,1,1 -Trifluoro-3-(naphthalen-2-ylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluorophenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dimethoxyphenylsulfanyl)- 1 , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dimethylphenylsulfanyl)-l,l,l-tπfluoro-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol;
3-(2,6-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol;
3-(2-Ethylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
2-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]benzoic acid methyl ester;
1,1,1 -Trifluoro-2-(l -phenyl- IH- indazol-5-yl)-3~(4-trifluoromethylpyrimidin-2- ylsulfanyl)propan-2-ol;
3-(3 ,5-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol; 3 -(3 ,5 -B is-trifluoromethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3-(2,4-Difluorophenylsulfanyl)-l , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenylsulfanyl)-l,l,l-tπfluoiO-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2-trifluoromethylphenylsulfanyl)propan-2-ol;
3-(3,4-Difluorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3 -Ethoxyphenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(4-tert-Butylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propylsulfanyl]phenyl}acetamide;
3-(4-Bromophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluoiOphenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3 -(pyridin-2-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-nitrophenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-o-tolylsulfanylpropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-m-tolylsulfanylpropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-p-tolylsulfanylpropan-2-ol;
3-(3-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,4-Dimethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(5 -tert-Butyl-2-methylpheny lsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trimethylphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- IH- indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-methylsulfanylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2-Chloro-6-methylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2-terM3utylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoiOmethylpyridin-2-ylsulfanyl)propan- 2-ol;
l,l,l-TrifluoiO-2-(l-phenyl-lH-indazol-5-yl)-3-(3-trifluoromethoxyphenylsulfanyl)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-methylindol- 1 -yl)propan-2-ol; 3-[2-(4-Chlorophenyl)indol- 1 -yl]- 1 ,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydiOxypiOpyl}-lH-indol-3- yl)acetonitrile;
l,l,l-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(6-methoxyindol-l-yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-S-ylj-S-CS-methylindol- l-yl)propan-2-ol;
3-(4-Benzyloxyindol-l-yl)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(4-Chloroindol-l -yl)-l , 1 , 1 -trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(6-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(6-methylindol-l-yl)propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-4- carboxylic acid methyl ester;
1,1,1 -Trifluoro-3-(6-fluoroindol-l -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1 - { 3 ,3 ,3 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-2-hydroxypropyl} - 1 H-indole-3 - carboxylic acid methyl ester;
2,2,2-Trifluoro-l-(l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indo 1-3 -yl)ethanone;
1,1,1 -Trifluoro-3-(4-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol; N-[2-(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}- lH-indol-3-yl)ethyl]acetamide;
3-(7-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluoiOphenyl)-lH-indazol-5-yl]propan-2-ol;
3-(7-Chloroindol-l -yl)- 1 , 1 , 1 -trifluoro-2-[l -(4-fluoiOphenyl)-lH-indazol-5-yl]propan-2-ol;
(2-Methyl-l-{3,3,3-tπfluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypiOpyl}-lH- indol-3-yl)acetic acid ethyl ester;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}-lH-indole-5- carboxylic acid methyl ester;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methyl-5-nitroindol-l-yl)propan- 2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3 - [2-(4-fluorophenyl)indol- 1 - yl]propan-2-ol;
3 -(4-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(6-Bromoindol- 1-yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(3-Dimethylaminomethyl-6-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol;
(5-Methoxy- 1 - { 3 ,3 ,3 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-2-hydroxypropyl } - 1 H- indol-3-yl)acetonitrile;
(5-Benzyloxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3-yl)acetonitrile; l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indole-6- carboxylic acid methyl ester;
l,l,l-TrifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-nitroindol-l-yl)piOpan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indole-4- carbonitrile;
3-(5-Benzyloxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]piOpan-2-ol;
l-{3,3,3-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}-lH-indole-5- carbonitrile;
3 -(3 -Dimethylaminomethyl-5-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5-methoxy-2-methylindol-l - yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-methylindol- 1 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(3-methylindol-l -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l-(4-fluoiOphenyl)- lH-indazol-5-yl]-3-(7-methylindol- 1 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5-nitroindol-l -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(2-phenylindol- 1 -yl)propan-2-ol;
(2-Phenyl-l-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}-lH- indol-3 -yl)acetonitrile; l,l,l-TπfluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-pyrrolo[2,3-c]pyridin-l-ylpropan-2- ol;
3-(7-Ethylindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3 -(2,3-Dimethyl-5-nitroindol- 1 -yl)- 1 , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
l,l,l-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(6-trifluoiOmethylindol-l-yl)piOpan- 2-ol;
1,1,1 -TrifluoiO-3-(7-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-6- carbonitrile;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-indol-l-ylpropan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-pyrrolo[2,3-δ]pyridin-l-ylpropan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-2- carboxylic acid ethyl ester;
3-(2,3-Dimethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-3- carbonitrile;
l-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)ethanone; 3-(3-Dimethylaminomethylindol-l-yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(3-Dimethylaminomethyl-5-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indol-3- yl)acetic acid ethyl ester;
2-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)acetamide;
3-(5-Bromoindol- 1 -yl)- 1 , 1 , l-trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-3-(5-fluoroindol-l-yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(5-Chloroindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -3 -(5-methoxyindol- 1 -yl)propan-2-ol;
3-(5,6-Dimethoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-nitroindol- 1 -yl)propan-2-ol;
5-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indole-2-carboxylic acid ethyl ester,
or a tautomer, prodrug, solvate, or salt thereof.
The invention also provides a method of making a compound of Formula (IA)
Figure imgf000075_0001
wherein: C is CH2, D is CR4R5 (where R4 is CF3 and R5 is OH), E is a bond, and A, B, R1, R2, and R3 are as defined above, the method comprising: (a) reacting the nitrile of Formula (II) with a suitable reducing agent, such as diisopropyl aluminum hydride, in a suitable solvent, such as dichloromethane, to provide an aldehyde of Formula (III)
Figure imgf000075_0002
Il III ;
(b) reacting the aldehyde of Formula (III) with [l,3]dithian-2-yltrimethylsilane (IV) in the presence of a suitable base, such as rø-butyl lithium, in a suitable solvent, such as THF, to provide a thioketene acetal of Formula (V)
Figure imgf000075_0003
III IV V ;
(c) reacting the thioketene acetal of Formula (V) with triethylsilane in the presence of an acid, such as TFA, in a solvent, such as dichloromethane, to give a thioketal of Formula (VI)
Figure imgf000075_0004
Vl (d) reacting the thioketal of Formula (VI) with methyl iodide in a solvent, such as acetonitrile, to provide an aldehyde of Formula (VII)
Figure imgf000076_0001
Vl VII ;
(e) reacting the aldehyde of Formula (VII) with (trifluoromethyl)trimethylsilane in the presence of a suitable source of fluoride, such as tetrabutylammonium fluoride, in a suitable solvent, such as THF, to provide the alcohol of Formula (VIII)
Figure imgf000076_0002
C = CH,
VII VIII
(f) oxidizing the alcohol of Formula (VIII) in the presence of Dess-Martin periodinane in a suitable solvent, such as dichloromethane, to form a ketone of Formula (IX)
Dess-Martin periodinane
Figure imgf000076_0004
VIII IX ; and
(g) reacting the ketone of Formula (IX) with an organometallic reagent R3M, such as a Grignard reagent where M is MgBr, MgCl, or MgI, or an organolithium reagent where M is Li, in a suitable solvent, such as ether or THF, to form the compound of Formula (IA)
Figure imgf000076_0005
Alternatively, a compound of Formula (IA), wherein C is a bond, and A, B, D, E, R1, R2, and R3 are as defined above may be prepared by starting from the aldehyde of Formula (III) and following steps (e), (f), and (g).
The invention also provides a method for making a compound of Formula (IA), wherein R3 is NR6R7, OR8, or SR9, C is CH2, D is CR4R5 (where R4 is CF3 and R5 is OH), E is CH2, and A, B, R1, and R2 are as defined above, the method comprising: (a') reacting a ketone of Formula (IX) with a sulfur ylide of Formula (XI) in the presence of a suitable base, such as sodium hydride, in a suitable solvent, such as THF, to provide an epoxide of Formula (XII)
Figure imgf000077_0001
(b') reacting the epoxide of Formula (XII) with a compound R3H of Formula (XIII), optionally in the presence of a base, such as sodium hydride, in a suitable solvent, such as DMF, to provide the compound of Formula (IA). Alternatively, a compound of Formula (IA), wherein C is a bond and A, B, D, E, R1, R2, and R3 are as defined above may be prepared by starting from the aldehyde of Formula (III) and following steps (e), (f), (a'), and (b')
Figure imgf000077_0002
Alternatively, a compound of Formula (IA), wherein C is CH2, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a bond, may be made by starting from the aldehyde of Formula (VII) using the following process:
(a") reacting the aldehyde of Formula (VII) with an organometallic reagent R3M of Formula (X) such as a Grignard reagent (M is MgBr, MgCl, or MgI), or an organolithium reagent (M is Li), in a suitable solvent such as ether or THF, to form an alcohol of Formula (XIV)
Figure imgf000078_0001
(b") oxidizing the alcohol of the Formula (XIV) with Dess Martin's periodinane reagent in a suitable solvent such as dichloromethane or THF, to provide a ketone of Formula (XV)
Figure imgf000078_0002
(c") reacting the ketone of Formula (XV) with (trifluoromethyl)trimethylsilane in the presence of a suitable source of fluoride such tetrabutylammonium fluoride, in a suitable solvent such as THF to provide the compound of Formula (IA). Alternatively, a compound of Formula (IA), wherein C is a bond and A, B, D, E, R1, R2, and R3 are as defined above, may be prepared by starting from the aldehyde of Formula (III) and following steps (a"), (b"), and (c")
Figure imgf000078_0003
The instant invention is also directed to compounds of Formula (IB)
Figure imgf000078_0004
wherein:
R1 is aryl, heteroaryl or C3-C7 cycloalkyl each optionally independently substituted with one to three substituent groups selected from Ci-C3 alkyl, hydroxy, halogen, oxo, methoxy, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a methyl group, or thiomethyl wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;
R2 is hydrogen or a halogen;
A and B are each independently CH or N;
C and E are each independently a bond or a -CH2-;
D is -CR4R5-, wherein:
R4 is Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, carbocycle, heterocyclyl, aryl, heteroaryl, carbocycle-C[-C8 alkyl, aryl-Q-Cg alkyl, aryl-Ci-C8 haloalkyl, heterocyclyl-Ci-C8 alkyl, heteroaryl-Ci-C8 alkyl, carbocycle-C2-C8 alkenyl, aryl-C2-C8 alkenyl, heterocyclyl-C2-C8 alkenyl, or heteroaryl-C2-C8 alkenyl, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R4 is independently Ci-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, Ci-C3 alkoxy, aminocarbonyl, Ci-C3 alkylaminocarbonyl, C1-C3 dialkylaminocarbonyl, halogen, hydroxy, carboxy, cyano, trifiuoromethyl, nitro, or Ci- C3 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein R4 cannot be trifiuoromethyl,
R5 is -OH;
R3 is Ci-C6 alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, NR6R7, OR8, or SR9, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently aryl, heteroaryl, heterocyclyl,
C1-C5 alkyl, Ci-C5 alkenyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, C1-C5 alkanoyloxy, C1-C5 alkanoyl, aroyl, C1-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C1-C5 alkylaminocarbonyloxy, C1-C5 dialkylaminocarbonyloxy, C1-Cs alkanoylamino, C1-C5 alkoxycarbonylamino, C1-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, carboxyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from aryl, heteroaryl, heterocyclyl, acyl, Ci-C5 alkyl, Cj-C5 alkanoyloxy, Q-C5 alkanoyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, Ci-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a CJ-C5 alkyl, Ci-C5 cycloalkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or C1-C3 alkyl, and
R7, R8, and R9 are each independently Cj-C5 alkyl, Ci-C5 alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl optionally independently substituted with one to three substituent groups,
wherein each substituent group of R7, R8, and R9 is independently heteroaryl, heterocyclyl, Ci-C5 alkyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C5 alkanoyloxy, C1-C5 alkanoyl, aroyl, Cj-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, Ci-C5 alkylaminocarbonyloxy, Ci-C5 dialkylaminocarbonyloxy, Cj-C5 alkanoylamino, Cj-C5 alkoxycarbonylamino, Cj-C5 alkylsulfonylamino, aminosulfonyl, Cj-C5 alkylaminosulfonyl, Cj-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R7, R8, and R9 is optionally independently substituted with one to three substituent groups selected from heteroaryl, heterocyclyl, acyl, C1-Cs alkyl, C1-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, C1-C5 alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
One aspect of the invention includes compounds of Formula (IB), wherein:
R1 is aryl or heteroaryl optionally substituted with one to three substituent groups selected from hydroxy, halogen, or oxo;
R2 is hydrogen;
C is a bond;
E is a bond or -CH2-; and
D is -CR4R5-, wherein:
R4 is C1-C5 alkyl, C2-C5 alkenyl, C3-C6 cycloalkyl, phenyl, C3-C6 cycloalkyl-CrC3 alkyl, phenyl-C]-C3 alkyl, phenyl-Ci-C3 haloalkyl, C3-C6 cycloalkyl-C2-C3 alkenyl, phenyl-C2-
C3 alkenyl, each optionally independently substituted with one to three substituent groups, wherein each substituent group of R4 is independently CpC3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, Cj-C3 alkoxy, aminocarbonyl, Cj-C3 alkylaminocarbonyl, Cj-C3 dialkylaminocarbonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or Q- C3 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein R4 cannot be trifluoromethyl, and
R5 is -OH,
or a tautomer, prodrug, solvate, or salt thereof.
One aspect of the invention includes compounds of Formula (IB), wherein:
R1 is a phenyl optionally substituted with one to three halogen groups;
A is N;
B is CH;
D is -CR4R5-, wherein:
R4 is C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-methyl-, or benzyl, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R4 is independently methyl, methoxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or hydroxy, wherein R4 cannot be trifluoromethyl, and
R5 is -OH; and
R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1,2,3,4-tetrahydroisoquinoline, or N-ethyl-JV-methylbenzene-l,2-diamine, 1,2,3,4-tetrahydroquinoline, NR6R7, OR8, or SR9; each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently C1-Cs alkyl, heteroaryl, heterocyclyl, acyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, C1-Cs alkenyl, carboxyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C1-Cs alkyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or a methyl group, and
R7, R8, and R9 are each independently a phenyl, naphthyl, pyridyl, pyrimidyl, quinoline, isoquinoline, or indolyl optionally independently substituted with one to three substituent groups,
wherein each substituent group of R7, R8, and R9 is independently heterocyclyl, Ci-C5 alkyl, cycloalkyl, acyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
One aspect of the above embodiment includes compounds of Formula (IB), wherein: R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4- benzoxazine, 1,2,3,4-tetrahydroisoquinoline, or N-ethyl-iV-methylbenzene-l,2-diamine, 1 ,2,3 ,4-tetrahydroquinoline,
wherein each substituent group of R3 is independently Ci-C5 alkyl, acyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, C1-C5 alkenyl, carboxyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C1-C5 alkyl, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Q-
C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
Representative compounds of Formula (IB) according to the invention are appended hereto as Table IB, where column A is the compound name according to standard nomenclature and column B is the corresponding chemical structure.
Preferred compounds of Formula (IB) include the following:
Cyclopropylphenyl-(1 -phenyl- lH-indazol-5-yl)methanol;
CyclopiOpyl-(3,5-dichlorophenyl)-(l-phenyl-lH-indazol-5-yl)methanol;
1 -Cyclopropyl-2-phenyl- 1 -( 1 -phenyl- 1 H-indazol-5 -y l)ethanol; l-CyclopiOpyl-2-(3,5-dichloiOphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-CyclopiOpyl-l-(l-phenyl-lH-indazol-5-yl)-2-p-tolylethanol;
l-Cyclopropyl-l-(l-phenyl-lH-indazol-5-yl)-2-rø-tolylethanol;
Cyclopropylphenyl-(l-phenyl-lH-benzotriazol-5-yl)methanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-benzotriazol-5-yl]phenylmethanol;
1 -(I -Phenyl- IH- indazol-5-yl)-l -quinolin-4-ylethanol;
1 -( 1 -Phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylpropan- 1 -ol;
1 -(4-Fluoronaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)propan- 1 -ol;
1 -( 1 - Ally 1- 1 H-indol-3 -yl)- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-methylpropan- 1 -ol; and
1 -(I -Allyl-lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan- 1 -ol,
or a tautomer, prodrug, solvate, or salt thereof.
The invention also provides a method of making a compound of Formula (IB)
Figure imgf000085_0001
wherein: A, B, C, D, E, R1, R2, and R3 are as defined above, the method comprising:
(a) reacting a nitrile of Formula (II) with an organometallic reagent R4-M of Formula (XVI) such as a Grignard reagent (M is MgBr, MgCl, or MgI), in a suitable solvent, such as TFIF or ether, to obtain the ketone of Formula (XVII)
Figure imgf000086_0001
(b) reacting the ketone of Formula (XVII) with an organometallic reagent R3M of Formula (X) such as a Grignard reagent (M is MgBr, MgCl, or MgI), or an organolithium reagent (M is Li), in a suitable solvent, such as ether or TFDF, to provide the compound of Formula (IB)
Figure imgf000086_0002
Alternatively, a compound of Formula (IB), wherein C is a bond or CH2, D is CR4R5 (where R5 is OH), and E is a bond, and A, B, R1, R2, R3, and R4 are as defined above may be prepared by starting from the ketone of Formula (XV) using the following step:
(a') reacting the ketone of Formula (XV) with an organometallic reagent R4M of Formula (XVI) such as a Grignard reagent (M is MgBr, MgCl, or MgI), or an organolithium reagent (M is Li), in a suitable solvent, such as ether or THF, to provide the compound of Formula (IB)
Figure imgf000086_0003
XV XVI IB
Alternatively, a compound of Formula (IB), wherein R3 is NR6R7, OR8, or SR9, C is a bond or
CH2, D is CR4R5 (where R5 is OH), and E is CH2, and A, B, R1, R2, and R4 are as defined above, may be prepared by starting from the aldehyde of Formula (III) or (VII):
(a") reacting the aldehyde of Formula (III) or (VII) with an organometallic reagent R4M of
Formula (XVI), such as a Grignard reagent (M is MgBr, MgCl, or MgI), or an organolithium reagent (M is Li), in a suitable solvent, such as THF or ether, to obtain the alcohol of Formula (XVIII)
Figure imgf000087_0001
or VII XVI XVIII
(b") oxidizing the alcohol of Formula (XVIII) in the presence of Dess-Martin periodinane in a suitable solvent, such as dichloromethane, to form a ketone of Formula (XIX)
Figure imgf000087_0002
XVIII XIX
(c") reacting the ketone of Formula (XIX) with the sulfur ylide of Formula (XI) in the presence of a suitable base such as sodium hydride in a suitable solvent, such as THF, to provide an epoxide of Formula (XX)
Figure imgf000087_0003
XIX Xl XX ; and
(d") reacting the epoxide of the Formula (XX) with a compound R3H of Formula (XIII), either without or with a base such as sodium hydride, in a suitable solvent, such as DMF, to provide a compound of Formula (IB)
Figure imgf000087_0004
In another aspect of the invention, the compounds according to the invention are formulated into pharmaceutical compositions comprising an effective amount, preferably a pharmaceutically effective amount, of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof, and a pharmaceutically acceptable excipient or carrier.
The invention also provides a method of modulating the glucocorticoid receptor function in a patient, the method comprising administering to the patient an effective amount of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
The invention further provides a method of treating a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
In addition, the invention also provides a method of treating a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof.
The invention provides a method of treating a disease characterized by inflammatory, allergic, or proliferative processes, in a patient in need of such treatment, the method comprising administering to the patient an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof. In a preferred embodiment of the invention, the disease characterized by inflammatory, allergic, or proliferative processes is selected from: (i) lung diseases (ii) rheumatic diseases or autoimmune diseases or joint diseases (iii) allergic diseases (iv) vasculitis diseases (v) dermatological diseases (vi) renal diseases (vii) hepatic diseases (viii) gastrointestinal diseases (ix) procto logical diseases (x) eye diseases (xi) diseases of the ear, nose, and throat (ENT) area (xii) neurological diseases (xiii) blood diseases (xiv) tumor diseases (xv) endocrine diseases (xvi) organ and tissue transplantations and graft-versus-host diseases (xvii) severe states of shock (xviii) substitution therapy; and (xix) pain of inflammatory genesis. In another preferred embodiment of the invention, the disease characterized by inflammatory, allergic, or proliferative processes is selected from: type I diabetes, osteoarthritis, Guillain-Barre syndrome, restenosis following percutaneous transluminal coronary angioplasty, Alzheimer disease, acute and chronic pain, atherosclerosis, reperfusion injury, bone resorption diseases, congestive heart failure, myocardial infarction, thermal injury, multiple organ injury secondary to trauma, acute purulent meningitis, necrotizing enterocolitis, and syndromes associated with hemodialysis, leukopheresis, and granulocyte transfusion.
The invention further provides methods of treating the disease-states or conditions mentioned above, in a patient in need of such treatment, the methods comprising sequentially or simultaneously administering to the patient: (a) an effective amount of a pharmaceutically acceptable compound according to the invention or a tautomer, prodrug, solvate, or salt thereof; and (b) a pharmaceutically acceptable glucocorticoid.
The invention further provides a method of assaying the glucocorticoid receptor function in a sample, comprising: (a) contacting the sample with a selected amount of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof; and (b) detecting the amount of the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof bound to glucocorticoid receptors in the sample. In a preferred embodiment of the invention, the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof is labeled with a detectable marker selected from: a radiolabel, fluorescent tag, a chemiluminescent tag, a chromophore, and a spin label.
The invention also provides a method of imaging the glucocorticoid receptor distribution in a sample or patient, the method comprising: (a) contacting the sample or administering to a patient a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof having a detectable marker (b) detecting the spatial distribution and amount of the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof having a detectable marker bound to glucocorticoid receptors in the sample or patient using an imaging means to obtain an image; and (c) displaying an image of the spatial distribution and amount of the compound according to the invention or a tautomer, prodrug, solvate, or salt thereof having a detectable marker bound to glucocorticoid receptors in the sample. In a preferred embodiment of the invention, the imaging means is selected from: radioscintigraphy, nuclear magnetic resonance imaging (MRJ), computed tomography (CT scan), or positron emission tomography (PET).
The invention also provides a kit for the in vitro diagnostic determination of the glucocorticoid receptor function in a sample, comprising: (a) a diagnostically effective amount of a compound according to the invention or a tautomer, prodrug, solvate, or salt thereof; and (b) instructions for use of the diagnostic kit.
Definition of Terms and Conventions Used Terms not specifically defined herein should be given the meanings that would be given to them by one of skill in the art in light of the disclosure and the context. As used in the specification and appended claims, however, unless specified to the contrary, the following terms have the meaning indicated and the following conventions are adhered to.
A. Chemical Nomenclature, Terms, and Conventions
In the groups, radicals, or moieties defined below, the number of carbon atoms is often specified preceding the group, for example, C1-CiO alkyl means an alkyl group or radical having 1 to 10 carbon atoms. The term "lower" applied to any carbon-containing group means a group containing from 1 to 8 carbon atoms, as appropriate to the group (i.e., a cyclic group must have at least 3 atoms to constitute a ring). In general, for groups comprising two or more subgroups, the last named group is the radical attachment point, for example, "alkylaryl" means a monovalent radical of the formula AIk-Ar-, while "arylalkyl" means a monovalent radical of the formula Ar-AIk- (where AIk is an alkyl group and Ar is an aryl group). Furthermore, the use of a term designating a monovalent radical where a divalent radical is appropriate shall be construed to designate the respective divalent radical and vice versa. Unless otherwise specified, conventional definitions of terms control and conventional stable atom valences are presumed and achieved in all formulas and groups.
The terms "alkyl" or "alkyl group" mean a branched or straight-chain saturated aliphatic hydrocarbon monovalent radical. This term is exemplified by groups such as methyl, ethyl, n- propyl, 1-methylethyl (isopropyl), ??-butyl, π-pentyl, 1,1 -dimethyl ethyl (tert-buty\), and the like. It may be abbreviated "AIk". The terms "alkenyl" or "alkenyl group" mean a branched or straight-chain aliphatic hydrocarbon monovalent radical containing at least one carbon-carbon double bond. This term is exemplified by groups such as ethenyl, propenyl, w-butenyl, isobutenyl, 3-methylbut-2-enyl, «-pentenyl, heptenyl, octenyl, decenyl, and the like.
The terms "alkynyl" or "alkynyl group" mean a branched or straight-chain aliphatic hydrocarbon monovalent radical containing at least one carbon-carbon triple bond. This term is exemplified by groups such as ethynyl, propynyl, »-butynyl, 2-butynyl, 3-methylbutynyl, n- pentynyl, heptynyl, octynyl, decynyl, and the like.
The terms "alkylene" or "alkylene group" mean a branched or straight-chain saturated aliphatic hydrocarbon divalent radical having the specified number of carbon atoms. This term is exemplified by groups such as methylene, ethylene, propylene, «-butylene, and the like, and may alternatively and equivalently be denoted herein as -(alkyl)-.
The terms "alkenylene" or "alkenylene group" mean a branched or straight-chain aliphatic hydrocarbon divalent radical having the specified number of carbon atoms and at least one carbon-carbon double bond. This term is exemplified by groups such as ethenylene, propenylene, «-butenylene, and the like, and may alternatively and equivalently be denoted herein as -(alkylenyl)-.
The terms "alkynylene" or "alkynylene group" mean a branched or straight-chain aliphatic hydrocarbon divalent radical containing at least one carbon-carbon triple bond. This term is exemplified by groups such as ethynylene, propynylene, n-butynylene, 2-butynylene, 3- methylbutynylene, M-pentynylene, heptynylene, octynylene, decynylene, and the like, and may alternatively and equivalently be denoted herein as -(alkynyl)-.
The terms "alkoxy" or "alkoxy group" mean a monovalent radical of the formula AIkO-, where AIk is an alkyl group. This term is exemplified by groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy, pentoxy, and the like. The terms "aryloxy", "aryloxy group", mean a monovalent radical of the formula ArO-, where Ar is aryl. This term is exemplified by groups such as phenoxy, naphthoxy, and the like.
The terms "alkylcarbonyl", "alkylcarbonyl group", "alkanoyl", or "alkanoyl group" mean a monovalent radical of the formula AIkC(O)-, where AIk is alkyl or hydrogen.
The terms "arylcarbonyl", "arylcarbonyl group", "aroyl" or "aroyl group" mean a monovalent radical of the formula ArC(O)-, where Ar is aryl.
The terms "acyl" or "acyl group" mean a monovalent radical of the formula RC(O)-, where R is a substituent selected from hydrogen or an organic substituent. Exemplary substituents include alkyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, and the like. As such, the terms comprise alkylcarbonyl groups and arylcarbonyl groups.
The terms "acylamino" or "acylamino group" mean a monovalent radical of the formula RC(O)N(R)-, where each R is a substituent selected from hydrogen or a substituent group.
The terms "alkoxycarbonyl" or "alkoxycarbonyl group" mean a monovalent radical of the formula AIkO-C(O)-, where AIk is alkyl. Exemplary alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, tert-butyloxycarbonyl, and the like.
The terms "aryloxycarbonyl" or "aryloxycarbonyl group" mean a monovalent radical of the formula ArO-C(O)-, where Ar is aryl.
The terms "alkylcarbonyloxy" or "alkylcarbonyloxy group" or "alkanoyloxy" or "alkanoyloxy group" mean a monovalent radical of the formula AIkC(O)O-, where AIk is alkyl.
The terms "arylcarbonyloxy" or "arylcarbonyloxy group" or "aroyloxy" or "aroyloxy group" mean a monovalent radical of the formula ArC(O)O-, where Ar is aryl.
The terms "alkylaminocarbonyloxy" or "alkylaminocarbonyloxy group" mean a monovalent radical of the formula R2NC(O)O-, where each R is independently hydrogen or lower alkyl. The term "alkoxycarbonylamino" or "alkoxycarbonylamino group" mean a monovalent radical of the formula ROC(O)NH-, where R is lower alkyl.
The terms "alkylcarbonylamino" or "alkylcarbonylamino group" or "alkanoylamino" or "alkanoylamino groups" mean a monovalent radical of the formula AIkC(O)NH-, where AIk is alkyl. Exemplary alkylcarbonylamino groups include acetamido (CHsC(O)NH-).
The terms "alkylaminocarbonyloxy" or "alkylaminocarbonyloxy group" mean a monovalent radical of the formula AlIcNHC(O)O-, where AIk is alkyl.
The terms "amino" or "amino group" mean an -NH2 group.
The terms "alkylamino" or "alkylamino group" mean a monovalent radical of the formula (AIk)NH-, where AIk is alkyl. Exemplary alkylamino groups include methylamino, ethylamino, propylamino, butylamino, tert-butylamino, and the like.
The terms "dialkylamino" or "dialkylamino group" mean a monovalent radical of the formula (AIk)(AIk)N-, where each AIk is independently alkyl. Exemplary dialkylamino groups include dimethylamino, methylethylamino, diethylamino, dipropylamino, ethylpropylamino, and the like.
The terms "substituted amino" or "substituted amino group" mean a monovalent radical of the formula -NR2, where each R is independently a substituent selected from hydrogen or the specified substituents (but where both Rs cannot be hydrogen). Exemplary substituents include alkyl, alkanoyl, aryl, arylalkyl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, and the like.
The terms "alkoxycarbonylamino" or "alkoxycarbonylamino group" mean a monovalent radical of the formula AIkOC(O)NH-, where AIk is alkyl. The terms "ureido" or "ureido group" mean a monovalent radical of the formula R2NC(O)NH-, where each R is independently hydrogen or alkyl.
The terms "halogen" or "halogen group" mean a fluoro, chloro, bromo, or iodo group.
The term "halo" means one or more hydrogen atoms of the group are replaced by halogen groups.
The terms "haloalkyl" or "haloalkyl group" mean a branched or straight-chain saturated aliphatic hydrocarbon monovalent radical, wherein one or more hydrogen atoms thereof are each independently replaced with halogen atoms. This term is exemplified by groups such as chloromethyl, 1,2-dibromoethyl, 1,1,1-trifluoropropyl, 2-iodobutyl, l-chloro-2-bromo-3- fluoropentyl, and the like.
The terms "sulfanyl", "sulfanyl group", "thioether", or "thioether group" mean a divalent radical of the formula -S-.
The terms "alkylthio" or "alkylthio group" mean a monovalent radical of the formula AIkS-, where AIk is alkyl. Exemplary groups include methylthio, ethylthio, «-propylthio, isopropylthio, «-butylthio, and the like.
The terms "arylthio" or "arylthio group" mean a monovalent radical of the formula ArS-, where Ar is aryl.
The terms "sulfinyl", "sulfmyl group", "thionyl", or "thionyl group" mean a divalent radical of the formula -SO-.
The terms "sulfonyl" or "sulfonyl group" mean a divalent radical of the formula -SO2-.
The terms "sulfonylamino" or "sulfonylamino group" mean a divalent radical of the formula -SO2NR-, where R is a hydrogen or a substituent group. The terms "aminosulfonyl" or "aminosulfonyl group" mean a monovalent radical of the formula NR2SO2-, where R is each independently a hydrogen or a substituent group.
The terms "carbocycle" or "carbocyclic group" mean a stable aliphatic 3- to 15-membered monocyclic or polycyclic monovalent or divalent radical consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7- membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the carbocycle may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. The term comprises cycloalkyl (including spiro cycloalkyl), cycloalkylene, cycloalkenyl, cycloalkenylene, cycloalkynyl, and cycloalkynylene, and the like.
The terms "cycloalkyl" or "cycloalkyl group" mean a stable aliphatic saturated 3- to 15- membered monocyclic or polycyclic monovalent radical consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7- membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the cycloalkyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. Exemplary cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, norbornane, adamantyl, tetrahydronaphthyl (tetralin), 1-decalinyl, bicyclo[2.2.2]octanyl, 1-methylcyclopropyl, 2-methylcyclopentyl, 2- methylcyclooctyl, and the like.
The terms "cycloalkenyl" or "cycloalkenyl group" mean a stable aliphatic 5- to 15-membered monocyclic or polycyclic monovalent radical having at least one carbon-carbon double bond and consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic ring.
Unless otherwise specified, the cycloalkenyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. Exemplary cycloalkenyl groups include cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, norbornenyl, 2- methylcyclopentenyl, 2-methylcyclooctenyl, and the like. The terms "cycloalkynyl" or "cycloalkynyl group" mean a stable aliphatic 8- to 15-membered monocyclic or polycyclic monovalent radical having at least one carbon-carbon triple bond and consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 8- to 10-membered monocyclic or 12- to 15-membered bicyclic ring. Unless otherwise specified, the cycloalkynyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. Exemplary cycloalkynyl groups include, cyclooctynyl, cyclononynyl, cyclodecynyl, 2-methylcyclooctynyl, and the like.
The terms "cycloalkylene" or "cycloalkylene group" mean a stable saturated aliphatic 3- to 15- membered monocyclic or polycyclic divalent radical consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7- membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the cycloalkyl ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. Exemplary cycloalkylene groups include cyclopentylene, and the like.
The terms "cycloalkenylene" or "cycloalkenylene group" mean a stable aliphatic 5- to 15- membered monocyclic or polycyclic divalent radical having at least one carbon-carbon double bond and consisting solely of carbon and hydrogen atoms which may comprise one or more fused or bridged ring(s), preferably a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic ring. Unless otherwise specified, the cycloalkenylene ring may be attached at any carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. Exemplary cycloalkenylene groups include cyclopentenylene, cyclohexenylene, cycloheptenylene, cyclooctenylene, cyclononenylene, cyclodecenylene, norbornenylene, 2-methylcyclopentenylene, 2- methylcyclooctenylene, and the like.
The terms "aryl" or "aryl group" mean an aromatic carbocyclic monovalent or divalent radical of from 6 to 14 carbon atoms having a single ring (e.g., phenyl or phenylene) or multiple condensed rings (e.g., naphthyl or anthranyl). Unless otherwise specified, the aryl ring may be attached at any suitable carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable carbon atom which results in a stable structure. Exemplary aryl groups include phenyl, naphthyl, anthryl, phenanthryl, indanyl, indenyl, biphenyl, and the like. It may be abbreviated "Ar".
The terms "heteroaryl" or "heteroaryl group" mean a stable aromatic 5- to 14-membered, monocyclic or polycyclic monovalent or divalent radical which may comprise one or more fused or bridged ring(s), preferably a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic radical, having from one to four heteroatoms in the ring(s) independently selected from nitrogen, oxygen, and sulfur, wherein any sulfur heteroatoms may optionally be oxidized and any nitrogen heteroatom may optionally be oxidized or be quaternized. Unless otherwise specified, the heteroaryl ring may be attached at any suitable heteroatom or carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable heteroatom or carbon atom which results in a stable structure. Exemplary and preferred heteroaryls include furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, indolyl, azaindolyl, dihydroindolyl, isoindolyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indazolyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzopyranone, purinyl, quinolizinyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, tetrahydroquinoxalinyl, isoquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl, acridine, and the like.
The terms "heterocycle", "heterocycle group", "heterocyclyl", or "heterocyclyl group" mean a stable non-aromatic 5- to 14-membered monocyclic or polycyclic, monovalent or divalent, ring which may comprise one or more fused or bridged ring(s), preferably a 5- to 7-membered monocyclic or 7- to 10-membered bicyclic ring, having from one to three heteroatoms in the ring(s) independently selected from nitrogen, oxygen, and sulfur, wherein any sulfur heteroatoms may optionally be oxidized and any nitrogen heteroatom may optionally be oxidized or be quaternized. Unless otherwise specified, the heterocyclyl ring may be attached at any suitable heteroatom or carbon atom which results in a stable structure and, if substituted, may be substituted at any suitable heteroatom or carbon atom which results in a stable structure. Exemplary and preferred heterocycles include pyrrolinyl, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuranyl, hexahydropyrimidinyl, hexahydropyridazinyl, 2,3- dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4-dihydro-2H-l,4-benzoxazine,l,2,3,4- tetrahydroisoquinoline, N-ethyl-iV -methylbenzene- 1 ,2-diamine, 1 ,2,3 ,4-tetrahydroquinoline and the like.
The term "compounds of the invention" and equivalent expressions are meant to embrace compounds of Formula (I) as herein described, including the tautomers, the prodrugs, the salts, particularly the pharmaceutically acceptable salts, and the solvates and hydrates thereof, where the context so permits. In general and preferably, the compounds of the invention and the formulas designating the compounds of the invention are understood to only include the stable compounds thereof and exclude unstable compounds, even if an unstable compound might be considered to be literally embraced by the compound formula. Similarly, reference to intermediates, whether or not they themselves are claimed, is meant to embrace their salts and solvates, where the context so permits. For the sake of clarity, particular instances when the context so permits are sometimes indicated in the text, but these instances are purely illustrative and it is not intended to exclude other instances when the context so permits.
The terms "optional" or "optionally" mean that the subsequently described event or circumstances may or may not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, "optionally substituted aryl" means that the aryl radical may or may not be substituted and that the description includes both substituted aryl radicals and aryl radicals having no substitution.
The terms "stable compound" or "stable structure" mean a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic or diagnostic agent. For example, a compound which would have a "dangling valency" or is a carbanion is not a compound contemplated by the invention. The term "substituted" means that any one or more hydrogens on an atom of a group or moiety, whether specifically designated or not, is replaced with a selection from the indicated group of substituents, provided that the atom's normal valency is not exceeded and that the substitution results in a stable compound. If a bond to a substituent is shown to cross the bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound, then such substituent may be bonded via any atom in such substituent. For example, when the substituent is piperazinyl, piperidinyl, or tetrazolyl, unless specified otherwise, such piperazinyl, piperidinyl, or tetrazolyl group may be bonded to the rest of the compound of the invention via any atom in such piperazinyl, piperidinyl, or tetrazolyl group. Generally, when any substituent or group occurs more than one time in any constituent or compound, its definition on each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0 to 2 R5, then such group is optionally substituted with up to two R5 groups and R5 at each occurrence is selected independently from the defined list of possible R5. Such combinations of substituents and/or variables, however, are permissible only if such combinations result in stable compounds.
In a specific embodiment, the term "about" or "approximately" means within 20%, preferably within 10%, and more preferably within 5% of a given value or range.
The yield of each of the reactions described herein is expressed as a percentage of the theoretical yield.
B. Salt, Prodrug, Derivative, and Solvate Terms and Conventions The terms "prodrug" or "prodrug derivative" mean a covalently-bonded derivative or carrier of the parent compound or active drug substance which undergoes at least some biotransformation prior to exhibiting its pharmacological effect(s). In general, such prodrugs have metabolically cleavable groups and are rapidly transformed in vivo to yield the parent compound, for example, by hydrolysis in blood, and generally include esters and amide analogs of the parent compounds. The prodrug is formulated with the objectives of improved chemical stability, improved patient acceptance and compliance, improved bioavailability, prolonged duration of action, improved organ selectivity, improved formulation (e.g., increased hydrosolubility), and/or decreased side effects (e.g., toxicity). In general, prodrugs themselves have weak or no biological activity and are stable under ordinary conditions. Prodrugs can be readily prepared from the parent compounds using methods known in the art, such as those described in A Textbook of Drug Design and Development. Krogsgaard-Larsen and H. Bundgaard (eds.), Gordon & Breach, 1991, particularly Chapter 5: "Design and Applications of Prodrugs"; Design of Prodrugs. H. Bundgaard (ed.), Elsevier, 1985; Prodrugs: Topical and Ocular Drug Delivery. K.B. Sloan (ed.), Marcel Dekker, 1998; Methods in Enzymology. K. Widder et al. (eds.), Vol. 42, Academic Press, 1985, particularly pp. 309-396; Burger's Medicinal Chemistry and Drug Discovery. 5th Ed., M. Wolff (ed.), John Wiley & Sons, 1995, particularly Vol. 1 and pp. 172-178 and pp. 949-982; Pro-Drugs as Novel Delivery Systems. T. Higuchi and V. Stella (eds.), Am. Chem. Soc, 1975; and Bioreversible Carriers in Drug Design. E.B. Roche (ed.), Elsevier, 1987, each of which is incorporated herein by reference in their entireties.
The term "pharmaceutically acceptable prodrug" as used herein means a prodrug of a compound of the invention which is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible.
The term "salt" means an ionic form of the parent compound or the product of the reaction between the parent compound with a suitable acid or base to make the acid salt or base salt of the parent compound. Salts of the compounds of the present invention can be synthesized from the parent compounds which contain a basic or acidic moiety by conventional chemical methods. Generally, the salts are prepared by reacting the free base or acid parent compound with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid or base in a suitable solvent or various combinations of solvents.
The term "pharmaceutically acceptable salt" means a salt of a compound of the invention which is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, generally water or oil-soluble or dispersible, and effective for their intended use. The term includes pharmaceutically-acceptable acid addition salts and pharmaceutically-acceptable base addition salts. As the compounds of the present invention are useful in both free base and salt form, in practice, the use of the salt form amounts to use of the base form. Lists of suitable salts are found in, e.g., S.M. Birge et al, J. Pharm. ScL, 1977, 66, pp. 1-19, which is hereby incorporated by reference in its entirety.
The term "pharmaceutically-acceptable acid addition salt" means those salts which retain the biological effectiveness and properties of the free bases and which are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, nitric acid, phosphoric acid, and the like, and organic acids such as acetic acid, trichloroacetic acid, trifluoroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 2-acetoxybenzoic acid, butyric acid, camphoric acid, camphorsulfonic acid, cinnamic acid, citric acid, digluconic acid, ethanesulfonic acid, glutamic acid, glycolic acid, glycerophosphoric acid, hemisulfic acid, heptanoic acid, hexanoic acid, formic acid, fumaric acid, 2-hydroxyethanesulfonic acid (isethionic acid), lactic acid, maleic acid, hydroxymaleic acid, malic acid, malonic acid, mandelic acid, mesitylenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, pamoic acid, pectinic acid, phenylacetic acid, 3-phenylpropionic acid, picric acid, pivalic acid, propionic acid, pyruvic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, tartaric acid, ^-toluenesulfonic acid, undecanoic acid, and the like.
The term "pharmaceutically-acceptable base addition salt" means those salts which retain the biological effectiveness and properties of the free acids and which are not biologically or otherwise undesirable, formed with inorganic bases such as ammonia or hydroxide, carbonate, or bicarbonate of ammonium or a metal cation such as sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Particularly preferred are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically-acceptable organic nontoxic bases include salts of primary, secondary, and tertiary amines, quaternary amine compounds, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion-exchange resins, such as methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2- diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tetramethylammonium compounds, tetraethylammonium compounds, pyridine, N,N-dimethylaniline, N-methylpiperidine, N- methylmorpholine, dicyclohexylamine, dibenzylamine, N,N-dibenzylphenethylamine, 1- ephenamine, NjN'-dibenzylethylenediamine, polyamine resins, and the like. Particularly preferred organic nontoxic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.
The term "solvate" means a physical association of a compound with one or more solvent molecules or a complex of variable stoichiometry formed by a solute (for example, a compound of Formula (I)) and a solvent, for example, water, ethanol, or acetic acid. This physical association may involve varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. In general, the solvents selected do not interfere with the biological activity of the solute. Solvates encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, methanolates, and the like.
The term "hydrate" means a solvate wherein the solvent molecule(s) is/are H2O.
The compounds of the present invention as discussed below include the free base or acid thereof, their salts, solvates, and prodrugs and may include oxidized sulfur atoms or quaternized nitrogen atoms in their structure, although not explicitly stated or shown, particularly the pharmaceutically acceptable forms thereof. Such forms, particularly the pharmaceutically acceptable forms, are intended to be embraced by the appended claims.
C. Isomer Terms and Conventions
The term "isomers" means compounds having the same number and kind of atoms, and hence the same molecular weight, but differing with respect to the arrangement or configuration of their atoms in space. The term includes stereoisomers and geometric isomers. The terms "stereoisomer" or "optical isomer" means a stable isomer that has at least one chiral atom or restricted rotation giving rise to perpendicular dissymmetric planes (e.g., certain biphenyls, allenes, and spiro compounds) and can rotate plane-polarized light. Because asymmetric centers and other chemical structure exist in the compounds of the invention which may give rise to stereoisomerism, the invention contemplates stereoisomers and mixtures thereof. The compounds of the invention and their salts include asymmetric carbon atoms and may therefore exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. Typically, such compounds will be prepared as a racemic mixture. If desired, however, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures.. As discussed in more detail below, individual stereoisomers of compounds are prepared by synthesis from optically active starting materials containing the desired chiral centers or by preparation of mixtures of enantiomeric products followed by separation or resolution, such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, use of chiral resolving agents, or direct separation of the enantiomers on chiral chromatographic columns. Starting compounds of particular stereochemistry are either commercially available or are made by the methods described below and resolved by techniques well-known in the art.
The term "enantiomers" means a pair of stereoisomers that are non-superimposable mirror images of each other.
The terms "diastereoisomers" or "diastereomers" mean stereoisomers which are not mirror images of each other.
The terms "racemic mixture" or "racemate" mean a mixture containing equal parts of individual enantiomers.
The term "non-racemic mixture" means a mixture containing unequal parts of individual enantiomers.
The term "geometrical isomer" means a stable isomer which results from restricted freedom of rotation about double bonds (e.g., c/>s-2-butene and frαrø-2-butene) or in a cyclic structure (e.g., cw-l,3-dichlorocyclobutane and trarø-l,3-dichlorocyclobutane). Because carbon-carbon double (olefinic) bonds, C=N double bonds, cyclic structures, and the like may be present in the compounds of the invention, the invention contemplates each of the various stable geometric isomers and mixtures thereof resulting from the arrangement of substituents around these double bonds and in these cyclic structures. The substituents and the isomers are designated using the cis/trans convention or using the E or Z system, wherein the term "E" means higher order substituents on opposite sides of the double bond, and the term "Z" means higher order substituents on the same side of the double bond. A thorough discussion of E and Z isomerism is provided in J. March, Advanced Organic Chemistry: Reactions. Mechanisms, and Structure, 4th ed., John Wiley & Sons, 1992, which is hereby incorporated by reference in its entirety. Several of the following examples represent single E isomers, single Z isomers, and mixtures of EIZ isomers. Determination of the E and Z isomers can be done by analytical methods such as X-ray crystallography, 1HNMR, and 13C NMR.
Some of the compounds of the invention can exist in more than one tautomeric form. As mentioned above, the compounds of the invention include all such tautomers.
It is well-known in the art that the biological and pharmacological activity of a compound is sensitive to the stereochemistry of the compound. Thus, for example, enantiomers often exhibit strikingly different biological activity including differences in pharmacokinetic properties, including metabolism, protein binding, and the like, and pharmacological properties, including the type of activity displayed, the degree of activity, toxicity, and the like. Thus, one skilled in the art will appreciate that one enantiomer may be more active or may exhibit beneficial effects when enriched relative to the other enantiomer or when separated from the other enantiomer. Additionally, one skilled in the art would know how to separate, enrich, or selectively prepare the enantiomers of the compounds of the invention from this disclosure and the knowledge of the prior art.
Thus, although the racemic form of drug may be used, it is often less effective than administering an equal amount of enantiomerically pure drug; indeed, in some cases, one enantiomer may be pharmacologically inactive and would merely serve as a simple diluent.
For example, although ibuprofen had been previously administered as a racemate, it has been shown that only the S-isomer of ibuprofen is effective as an anti-inflammatory agent (in the case of ibuprofen, however, although the /2-isomer is inactive, it is converted in vivo to the S- isomer, thus, the rapidity of action of the racemic form of the drug is less than that of the pure ^-isomer). Furthermore, the pharmacological activities of enantiomers may have distinct biological activity. For example, iS'-penicillamine is a therapeutic agent for chronic arthritis, while ^-penicillamine is toxic. Indeed, some purified enantiomers have advantages over the racemates, as it has been reported that purified individual isomers have faster transdermal penetration rates compared to the racemic mixture. See U.S. Patent Nos. 5,114,946 and 4,818,541.
Thus, if one enantiomer is pharmacologically more active, less toxic, or has a preferred disposition in the body than the other enantiomer, it would be therapeutically more beneficial to administer that enantiomer preferentially. In this way, the patient undergoing treatment would be exposed to a lower total dose of the drug and to a lower dose of an enantiomer that is possibly toxic or an inhibitor of the other enantiomer.
Preparation of pure enantiomers or mixtures of desired enantiomeric excess (ee) or enantiomeric purity are accomplished by one or more of the many methods of (a) separation or resolution of enantiomers, or (b) enantioselective synthesis known to those of skill in the art, or a combination thereof. These resolution methods generally rely on chiral recognition and include, for example, chromatography using chiral stationary phases, enantioselective host- guest complexation, resolution or synthesis using chiral auxiliaries, enantioselective synthesis, enzymatic and nonenzymatic kinetic resolution, or spontaneous enantioselective crystallization. Such methods are disclosed generally in Chiral Separation Techniques: A Practical Approach (2nd Ed.), G. Subramanian (ed.), Wiley- VCH, 2000; T.E. Beesley and R.P.W. Scott, Chiral Chromatography, John Wiley & Sons, 1999; and Satinder Ahuja, Chiral Separations by Chromato graphy , Am. Chem. Soc, 2000. Furthermore, there are equally well-known methods for the quantitation of enantiomeric excess or purity, for example, GC, HPLC, CE, or NMR, and assignment of absolute configuration and conformation, for example, CD ORD, X-ray crystallography, or NMR. In general, all tautomeric forms and isomeric forms and mixtures, whether individual geometric isomers or stereoisomers or racemic or non-racemic mixtures, of a chemical structure or compound is intended, unless the specific stereochemistry or isomeric form is specifically indicated in the compound name or structure.
D. Pharmaceutical Administration and Diagnostic and Treatment Terms and
Conventions The term "patient" includes both human and non-human mammals.
The term "effective amount" means an amount of a compound according to the invention which, in the context of which it is administered or used, is sufficient to achieve the desired effect or result. Depending on the context, the term effective amount may include or be synonymous with a pharmaceutically effective amount or a diagnostically effective amount.
The terms "pharmaceutically effective amount" or "therapeutically effective amount" means an amount of a compound according to the invention which, when administered to a patient in need thereof, is sufficient to effect treatment for disease-states, conditions, or disorders for which the compounds have utility. Such an amount would be sufficient to elicit the biological or medical response of a tissue, system, or patient that is sought by a researcher or clinician. The amount of a compound of according to the invention which constitutes a therapeutically effective amount will vary depending on such factors as the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of treatment, the type of disease-state or disorder being treated and its severity, drugs used in combination with or coincidentally with the compounds of the invention, and the age, body weight, general health, sex, and diet of the patient. Such a therapeutically effective amount can be determined routinely by one of ordinary skill in the art having regard to their own knowledge, the prior art, and this disclosure.
The term "diagnostically effective amount" means an amount of a compound according to the invention which, when used in a diagnostic method, apparatus, or assay, is sufficient to achieve the desired diagnostic effect or the desired biological activity necessary for the diagnostic method, apparatus, or assay. Such an amount would be sufficient to elicit the biological or medical response in a diagnostic method, apparatus, or assay, which may include a biological or medical response in a patient or in a in vitro or in vivo tissue or system, that is sought by a researcher or clinician. The amount of a compound according to the invention which constitutes a diagnostically effective amount will vary depending on such factors as the compound and its biological activity, the diagnostic method, apparatus, or assay used, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of administration, drugs and other compounds used in combination with or coincidentally with the compounds of the invention, and, if a patient is the subject of the diagnostic administration, the age, body weight, general health, sex, and diet of the patient. Such a diagnostically effective amount can be determined routinely by one of ordinary skill in the art having regard to their own knowledge, the prior art, and this disclosure.
The term "modulate" means the ability of a compound to alter the function of the glucocorticoid receptor by, for example, binding to and stimulating or inhibiting the glucocorticoid receptor functional responses.
The term "modulator" in the context of describing compounds according to the invention means a compound that modulates the glucocorticoid receptor function. As such, modulators include, but are not limited to, agonists, partial agonists, antagonists, and partial antagonists.
The term "agonist" in the context of describing compounds according to the invention means a compound that, when bound to the glucocorticoid receptor, enhances or increases the glucocorticoid receptor function. As such, agonists include partial agonists and full agonists.
The term "full agonist" in the context of describing compounds according to the invention means a compound that evokes the maximal stimulatory response from the glucocorticoid receptor, even when there are spare (unoccupied) glucocorticoid receptors present.
The term "partial agonist" in the context of describing compounds according to the invention means a compound that is unable to evoke the maximal stimulatory response from the glucocorticoid receptor, even at concentrations sufficient to saturate the glucocorticoid receptors present.
The term "antagonist" in the context of describing compounds according to the invention means a compound that directly or indirectly inhibits or suppresses the glucocorticoid receptor function. As such, antagonists include partial antagonists and full antagonists.
The term "full antagonist" in the context of describing compounds according to the invention means a compound that evokes the maximal inhibitory response from the glucocorticoid receptor, even when there are spare (unoccupied) glucocorticoid receptors present.
The term "partial antagonist" in the context of describing compounds according to the invention means a compound that is unable to evoke the maximal inhibitory response from the glucocorticoid receptor, even at concentrations sufficient to saturate the glucocorticoid receptors present.
The terms "treating" or "treatment" mean the treatment of a disease-state in a patient, and include:
(i) preventing the disease-state from occurring in a patient, in particular, when such patient is genetically or otherwise predisposed to the disease-state but has not yet been diagnosed as having it; (ii) inhibiting or ameliorating the disease-state in a patient, i.e., arresting or slowing its development; or
(iii) relieving the disease-state in a patient, i.e., causing regression or cure of the disease- state.
General Synthetic Methods for Making Compounds of Formula (IA) and (IB) The invention also provides processes for making compounds of Formula (IA) and (IB). In all schemes, unless specified otherwise, A, B, C, D, E, R1, R2, and R3 in the formulas below shall have the meaning of A, B, C, D, E, R1, R2, and R3 in the Formula (IA) and (IB) of the invention described hereinabove. Intermediates used in the preparation of compounds of the invention are either commercially available or readily prepared by methods known to those skilled in the art.
Optimum reaction conditions and reaction times may vary depending on the particular reactants used. Unless otherwise specified, solvents, temperatures, pressures, and other reaction conditions may be readily selected by one of ordinary skill in the art. Specific procedures are provided in the Synthetic Examples section. Typically, reaction progress may be monitored by thin layer chromatography (TLC), if desired, and intermediates and products may be purified by chromatography on silica gel and/or by recrystallization.
Compounds of Formula (IA) may be prepared by the method outlined in Scheme I.
Figure imgf000109_0001
wherein C is a bond or CH2, C is a bond or CH2, D is CR4R5, R4 is CF3 and D is CR4R5, R4 is CF3 and R5 is OH, and R5 is OH, and E is a bond E is CH2.
Scheme I As illustrated in Scheme I, nitrile is reduced with a suitable reducing agent, such as diisopropyl aluminum hydride, in a suitable solvent, such as dichloromethane or THF, to produce an aldehyde (III). Condensations of aldehydes are well known in the art and the [l,3]dithian-2- yltrimethylsilane anion can be condensed with the aldehyde (III) in a suitable solvent, such as THF or diethyl ether, to provide a thioketene acetal (V). Reduction of the double bond of the thioketene acetal (V) in the presence of triethylsilane and a suitable acid, such as TFA, in a suitable solvent, such as dichloromethane, provides thioacetal (VI). Deprotection of the thioacetal (VI) in the presence of iodomethane in a suitable solvent, such as acetonitrile, provides an aldehyde (VII). Nucleophilic additions to aldehydes is well known in the art and the trifluoromethyl anion can be added to the aldehyde (VII) in a suitable solvent, such as THF, or diethyl ether, to provide a secondary alcohol (VIII). Oxidation of the alcohol (VIII) in the presence of a suitable oxidizing reagent, such as Dess-Martin's periodinane or manganese dioxide, in a suitable solvent, such as dichloromethane or acetone, provides a ketone (IX). Reaction of the ketone (IX) with a suitable organometallic reagent R3M, such as a Grignard reagent (M is MgBr or MgCl) or an organolithium reagent (M is Li), in a suitable solvent, such as THF or diethyl ether, provides the desired compound of Formula (IA) wherein C is CH2, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a bond. Alternatively, a compound of Formula (IA), when C is a bond, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a bond, may be prepared by starting from the aldehyde (III) and following steps (f), (g), and (h) shown in Scheme I.
Reaction of the ketone (IX) with a sulfur ylide in a suitable solvent, such as THF or diethyl ether, provides an epoxide (XII). Cleavage of epoxides is well known in the art, and may be achieved by the addition of nucleophiles or organometallic reagents. The epoxide (XII) can be cleaved by the addition of organometallic reagents R3M, such as a Grignard reagent (M is MgBr or MgCl) or an organolithium reagent (M is Li), in a suitable solvent, such as THF or diethyl ether. Cleavage of the epoxide (XII) may also be achieved by reacting with nucleophiles R3H such as amines (where R3 is NR6R7), alcohols (where R3 is OR8), or thiols (where R3 is SR9) either with or without a base in a suitable solvent, such as DMF or DMSO, to provide the compound of Formula (IA), where C is CH2, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a CH2. Alternatively, compound of Formula (IA) where C is a bond, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a CH2, may be obtained by starting with the aldehyde (III) and following the steps (f), (g), (i), and Q) shown in Scheme I.
Reaction of the aldehyde (VII) with a suitable organometallic reagent R3M, such as a Grignard reagent (M is MgBr or MgCl) or an organolithium reagent (M is Li), in a suitable solvent, such as THF or diethyl ether, provides a secondaiy alcohol (XIV). Oxidation of the alcohol (XIV) in the presence of a suitable oxidizing reagent, such as Dess-Martin's periodinane, in a suitable solvent, such as dichloromethane or acetone, provides a ketone (XV). Reaction of the ketone (XV) with (trifluoromethyl)trimethylsilane in the presence of a suitable source of fluoride, such as tetrabutylammonium fluoride, in a suitable solvent, such as THF or diethyl ether, provides the compound of Formula (IA) where C is CH2, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a bond. Alternatively, the compound of Formula (IA) where C is a bond, D is CR4R5 (where R4 is CF3 and R5 is OH), and E is a bond, may be obtained by starting with the aldehyde (III) and following steps (e), (k), and (1) of Scheme I.
Compounds of Formula (IB) may be prepared by the method outlined in Scheme II.
nucleophilic addition
Figure imgf000111_0001
Figure imgf000111_0002
Scheme II
Reaction of nitriles with Grignard reagents is well known in the art. As illustrated in Scheme II, reacting a nitrile (II) with a Grignard reagent R4M (M is MgBr or MgCl) in a suitable solvent, such as THF or ether, provides a ketone (XVII). Reaction of the ketone (XVII) with organometallic reagents R3M, such as a Grignard reagent (M is MgBr or MgCl) or an organolithium reagent (M is Li), in a suitable solvent, such as THF or ether, provides the compound of Formula (IB).
Compounds of Formula (IB) may also be prepared by the method outlined in Scheme III. (a) nucleophilic addition
(e) nucleophilic addition
Figure imgf000112_0001
Figure imgf000112_0002
wherein C is a bond or CH2,
D is CR4R5, and D iS CR4R5, and R5 is OH, and R5 is OH, and E is CH,. E is a bond
Scheme III
As shown in Scheme III, reaction of an aldehyde (VII) with a suitable organometallic reagent R4M, such as a Grignard reagent (M is MgBr or MgCl), in a suitable solvent, such as THF or diethyl ether, provides a secondary alcohol (XVIII). Oxidation of the alcohol (XVIII) in the presence of a suitable oxidizing reagent, such as Dess-Martin's periodinane, in a suitable solvent, such as dichloromethane or acetone, provides a ketone (XIX). Reaction of the ketone (XIX) with a suitable organometallic reagent R3M, such as a Grignard reagent (M is MgBr or MgCl) or an organolithium reagent (M is Li), in a suitable solvent, such as THF or diethyl ether, provides the compound of Formula (IB) where C is CH2, D is CR4R5 (R5 is OH), and E is a bond.
Reaction of the ketone (XIX) with a sulfur ylide in a suitable solvent, such as THF or diethyl ether, provides an epoxide (XX). The epoxide (XX) can be cleaved by the addition of organometallic reagents R3M, such as a Grignard reagent (M is MgBr or MgCl) or an organolithium reagent (M is Li), in a suitable solvent, such as THF or diethyl ether. Cleavage of the epoxide (XX) may also be achieved by reacting with nucleophiles R3H such as amines (where R3 is NR6R7), alcohols (where R3 is OR8), or thiols (where R3 is SR9) either with or without a base in a suitable solvent, such as DMF or DMSO, to provide a compound of Formula (IB), where C is CH2, D is CR4R5 (where R5 is OH), and E is a CH2. Alternatively, a compound of Formula (IB) where C is a bond, D is CR4R5 (where R5 is OH), and E is a CH2, may be obtained by starting with the ketone (XVII) and following the steps (d) and (e). A method for making the benzotriazolonitrile (XXV) and the benzimidazole nitrile (XXVI) is outlined in Scheme IV.
Figure imgf000113_0001
XXl XXII XXIII
Figure imgf000113_0002
XXV XXIV XXVI
Scheme IV
As outlined in Scheme IV, an optionally substituted chloronitrobenzonitrile (XXI) is reacted with an optionally substituted aniline (XXII) in the presence of diisopropylethylamine in a suitable solvent, such as DMF or DMA, to provide an optionally substituted aminonitrobenzonitrile (XXIII). The aminonitrobenzonitrile (XXIII) is reduced under hydrogen transfer conditions to a corresponding diaminobenzonitrile (XXIV). The optionally substituted diaminobenzonitrile (XXIV) is reacted with sodium nitrate in acetic acid to provide an optionally substituted benzotriazole (XXV). The optionally substituted diaminobenzonitrile (XXIV) is heated with trimethyl orthoformate in the presence of a suitable acid, such as p- toluene sulfonic acid, to provide an optionally substituted benzimidazole (XXVI).
An indazole nitrile (II), wherein A is N and B is CH, is prepared according to the known procedure of Halley et al., Syn. Commun., 1997, 27(7), pp. 1199-1207. An indolonitrile (II), wherein A is CH and B is CH, is prepared according to the known procedure of Antilla et al, J. Am. Chem. Soc, 2002, UA, pp. 11684-11688.
I l l In order that this invention be more fully understood, the following examples are set forth. These examples are for the purpose of illustrating embodiments of this invention, and are not to be construed as limiting the scope of the invention in any way since, as recognized by one skilled in the art, particular reagents or conditions could be modified as needed for individual compounds. Starting materials used are either commercially available or easily prepared from commercially available materials by those skilled in the art.
Experimental Examples
Example 1: 2,2,2-Trifluoro-l-phenyl-l-(l-phenyI-lH-indazol-5-yl)ethanol
Step (a): To a solution of 1 -phenyl- lH-indazole-5-carbonitrile (12.58 g, 57.38 mmol) in 300 mL of CH2Cl2 at O0C was added DIBAL-H (IM in THF, 80.33 mL, 80.33 mmol). The resulting yellow suspension was stirred for 2 hours and then poured into 150 mL of cold IN HCl solution. The biphasic system was cooled to O0C and then basified to pH 8 by the addition of saturated aqueous sodium bicarbonate (NaHCOs) solution. The aqueous layer was extracted with three 100 mL portions of CH2Cl2. The combined organic phase was dried over sodium sulfate (Na2SO4), filtered, and then concentrated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-80% hexanes/EtOAc). The desired product 1 -phenyl- lH-indazole-5-carbaldehyde was obtained as a light yellow solid (8.8 g, 69% yield; M+Η÷: 223).
Step (b): To a solution of l-phenyl-lH-indazole-5-carbaldehyde (6.0 g, 27.0 mmol) in 50 mL of TΗF at O0C was added a solution Of TMSCF3 in TΗF (4.5 g, 31.8 mmol). The resulting light yellow solution was stirred at O0C for 15 minutes, then tetrabutylammonium fluoride (TBAF) (IM in TΗF, 7.8 mL, 7.8 mmol) was added. The reaction mixture was allowed to warm up to room temperature and then stirred for an additional 14 hours. The THF was evaporated in vacuo and the resulting residue was dissolved in 100 mL of EtOAc, washed with three 25 mL portions of water, and a 25 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 80% hexanes/EtOAc). The desired product 2,2,2- trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol was obtained as a light yellow solid (7.1 g, 88.0% yield; M+Η+: 293).
Step (c): A suspension of Dess-Martin periodinane (11.9 g, 28.0 mmol) and 2,2,2-trifluoro-l- (l-phenyl-lH-indazol-5-yl)ethanol (7.0 g, 24.0 mmol) in 100 mL of CH2Cl2 was allowed to stir for 12 hours at room temperature. The reaction mixture was added to 150 mL of hexane and the resulting white precipitate was filtered through a pad of CELITE® filter aid. The combined organic solution was washed with three 25 mL portions of aqueous saturated sodium bicarbonate solution and a 25 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 85% hexanes/EtOAc) The desired product 2,2,2- trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanone was obtained as a white solid (6.3 g, 91.0% yield; M+Η+: 291).
Step (d): To a solution of 2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanone (50.0 mg, 0.2 mmol) in 0.5 mL of TΗF was added phenylmagnesium bromide (1.0 M, 1.0 mL, 1.0 mmol) at room temperature. The solution was stirred at this temperature for 12.0 hours. The reaction was quenched with 2 mL of saturated aqueous ammonium chloride (NH4Cl) solution and 3.0 mL of water. The aqueous layer was extracted with three 5 mL portions of EtOAc and the combined organic layers were dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-85% hexanes/EtOAc). The desired product 2,2,2-trifluoro-l- phenyl-1 -(I -phenyl- lH-indazol-5-yl)ethanol was obtained as a white solid (51.0 mg, 80% yield; MMJ+: 369). The following examples were synthesized following the procedure illustrated for Example 1, step (d), using the corresponding Grignard or equivalent organometallic reagent. The percent yield of the reaction and the MH-H+ are indicated in parentheses.
l-Biphenyl-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (72%, M+Η+: 445);
l-CS^-DifluoiOphenyO^^^-trifluoro-l-Cl-phenyl-lH-indazol-S-yOethanol (63%, M+H+: 405);
l-(3,5-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (82%, MH-H+: 405);
l-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro-l-(l-ρhenyl-lH-indazol-5-yl)ethanol (66%, M+Η4": 421);
l-(4-ChloiO-3-methylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (72%, M+Η+: 417);
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (69%, MH-H+: 403);
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (75%, M+Η+: 421);
1 -(4-Chloro-3 -fluorophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol (68%, M+Η* : 421);
l-(3,5-Dichlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (48%, M+Η+: 438);
2,2,2-Trifluoro-l-naphthalen-l-yl-l -(I -phenyl- lH-indazol-5-yl)ethanol (80%, MH-H+: 419);
2,2,2-TrifluoiO-l-(3-fluorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (69%, MH-H+: 387); 2,2,2-Trifluoro- 1 -(4-methylnaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol (74%,
M+Η+: 433);
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (76%, M+Η+: 427);
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (26%, M+Η+: 427);
2,2,2-Trifluoro- l-(4-fluorophenyl)-l -(I -phenyl- lH-indazol-5-yl)ethanol (55%, M+Η+: 387);
2,2,2-TrifluoiO-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (83%,
M+Η4: 401);
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (39%, MH-H+: 413);
l-(4-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (76%, M+Η+: 403);
2,2,2-Trifluoro- 1 -(3 -morpholin-4-ylmethylphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol (78%, M+Η+: 468);
2,2,2-Trifluoro-l-(4-morpholin-4-ylmethylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (59%, M+Η+: 468);
2,2,2-Trifluoro-l-(l-phenyl-lH-indazol-5-yl)-l-(2,4,5-triraethylphenyl)ethanol (80%, M+Η+: 411);
2,2,2-Trifluoro-l-(l-phenyl-lH-indazol-5-yl)-l-(2,4,6-trimethylphenyl)ethanol (83%, M+Η+: 411); l-(4-te^-Butyl-2,6-dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (20%, M+Η+: 453);
2,2,2-Trifluoro-l-(3-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (79%, M+H+: 399);
l-(3,5-Dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (67%, M+Η"1": 397);
2,2,2-TrifluoiO-l-(4-methoxy-3,5-dimethylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (73%, M+Η+: 427);
2,2,2-Trifluoro-l-(4-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (65%, IVU-H+: 399);
l-(3,4-Dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (73%, M+Η4": 397);
2,2,2-Trifluoro- 1 -(3-fluoro-4-methoxyphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol (70%, M+Η+: 417);
2,2,2-Trifluoro- 1 -(5-fluoro-2-methoxyphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol (77%, M+Η+: 417);
1 -(2,5-Dimethoxyphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol (89%, M+Η1": 429);
2,2,2-Trifluoro- 1 -(2-morpholin-4-ylmethylphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol (76%, M+Η*: 468);
l-Biphenyl-2-yl-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol (73%, M+Η+: 445);
l-(2,5-Dimethoxyphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (89%, M+Η+: 429); 2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -(I -phenyl- 1 H-indazol-5-yl)ethanol (86%, M+Η+: 437);
2,2,2-Trifluoro-l-(6-methoxynaphthalen-2-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (82%, M+Η+: 449);
2,2,2-Trifluoro-l-naphthalen-2-yl-l-(l-phenyl-lH-indazol-5-yl)ethanol (73%, MH-H+: 419);
2,2,2-Trifluoro- 1 -(2-methylnaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol (47%,
M+Η+: 433);
1 -Benzo [δ]thiophen-3 -yl-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol (43%, M+Η1": 425); and
2,2,2-Trifluoro-l-(6-fluoropyridin-2-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (35%, M+Η"1": 388).
Resolution to the (+)- and (-)enantiomers was accomplished by chiral ΗPLC on a CΗIRALCEL™ AD-Η column, eluting with 20% isopropanol-hexanes.
Example 2: 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazoI-5-yl]-l-phenylethanol
Figure imgf000119_0001
Step (a): To a solution of l-(4-fluorophenyl)-lH-indazole-5-carbonitrile (2.0 g, 8.43 mmol) in 100 mL of CH2Cl2 at O0C was added DIBAL-H (IM in THF, 12.6 niL, 12.6 mmol). The resulting yellow suspension was stirred for 2 hours and then poured into 25 mL of cold IN HCl solution. The biphasic system was cooled to O0C and then basified to pH 8 by the addition of saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with three 50 mL portions of CH2Cl2. The combined organic phase was dried over sodium sulfate, filtered, and then concentrated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-80% EtOAc/hexanes) The desired product l-(4-fluorophenyl)-lH-indazole-5-carbaldehyde was obtained as a light yellow solid (1.4 g, 69% yield; M+Η+: 241).
Step (b): To a solution of l-(4-fluorophenyl)-lH-indazole-5-carbaldehyde (1.4 g, 6 mmol) in 10 mL of TΗF at O0C was added TMSCF3 (1.3 g, 9 mmol). The resulting light yellow solution was stirred at O0C for 15 minutes then TBAF solution (15 mL, 15 mmol) was added. The reaction mixture was allowed to warm up to room temperature and then stirred for an additional 14 hours. The TΗF was evaporated in vacuo and the resulting residue was dissolved in 100 mL of EtOAc, washed with three 25 mL portions of water and a 25 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 95%-70% EtOAc/hexanes). The desired product 2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol was obtained as a light yellow solid (1.3 g, 72% yield; M+Η+: 311).
Step (c): To a suspension of Dess-Martin periodinane (360 mg, 0.85 mmol) and 2,2,2-trifluoro- l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (217 mg, 0.7 mmol) in 3 mL of CH2Cl2 was allowed to stir for 12 hours at room temperature. The reaction mixture was added to 1 mL of hexane and the resulting white precipitate was filtered through a pad of CELITE® filter aid. The combined organic solution was washed with three mL portions of sodium bicarbonate and one 5 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 80% EtOAc/hexanes) The desired product 2,2,2-trifluoro-l-[l-(4-fluorophenyl)- lH-indazol-5-yl]ethanone was obtained as a white solid (200 mg, 93.0 yield%; M+Η+: 309). Step (d): To a solution of 2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanone (25.0 mg, 0.07 mmol) in 0.5 mL of TΗF was added phenylmagnesium bromide (1.0 M, 0.5 mL, 5.0 mmol) at room temperature. The solution was stirred at this temperature for 12.0 hours. The reaction was quenched with 2 mL of saturated aqueous ammonium chloride solution and 3.0 mL of water. The aqueous layer was extracted with three 5 mL portions of EtOAc and the combined organic layers were dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-85% EtOAc/hexanes). The desired product 2,2,2-trifluoro-l- phenyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol was obtained as a white and waxy oil (25.0 mg, 99% yield; M+Η+r 387).
The following examples were synthesized following the procedure illustrated for Example 2 step (d), using the corresponding Grignard or equivalent organometallic reagent with suitably functionalized indazole ketones. The percent yield of the reaction and the M+Η"1" are indicated in parentheses.
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (70%, M+Η+: 439);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol (97%, M+Η+: 437);
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]ethanol (94%, M+Η"1": 455);
2,2,2-Trifluoro- 1 -[l-(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(4-methylnaphthalen- 1 -yl)ethanol (58%, M+Η1": 451);
l-Benzo[δ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (64%, 443); 1 -(2,2-Difluoro- 1 ,3 -benzodioxol-4-yl)-2,2,2-trifluoro- 1 - [ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol (55%; M+rf": 467);
1 - 1 ,3-Benzodioxol-4-yl-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol (62%; M+Η+: 432);
2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-7-yl)ethanol (46%; M+H+: 427);
2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-7-yl)ethanol (53%; M+Η+: 440);
2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-5-yl)ethanol; (62%; M+Η+: 440);
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -(I -methyl- lH-indol-6-yl)ethanol; (61%; M+Η+: 440);
4- {2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}indole- 1 -carboxylic acid tot-butyl ester (70%; M+Η+: 527);
l-Methyl-4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- quinolin-2-one (27%; M+Η+: 469);
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol (79%, M+it: 438);
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol (83%, M+Η+: 404);
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol (75%, M+Η4": 406); 2,2,2-Trifluoro-l-ρhenyl-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol (87%, IVU-H+: 370);
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol (87%, M+Η+: 387);
2,2,2-Trifluoro-l -[I -(2-fluorophenyl)- lH-indazol-5-yl]- 1 -naphthalen- 1 -ylethanol (75%, MH-Pl+: 437);
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen-l -yl)- 1 -[I -(2-fluorophenyl)- lH-indazol-5-yl]ethanol (8PZo5 MH-H+: 454);
2,2,2-Trifluoro-l-ρhenyl-l-(l-p-tolyl-lH-indazol-5-yl)ethanol (77%, M-I-H+: 383);
2,2,2-Trifluoro-l-[l-(4-methoxyphenyl)-lH-indazol-5-yl]-l-phenylethanol (73%, M+Η+: 399);
2,2,2-TrifluoiO-l-phenyl-l-(l-o-tolyl-lH-indazol-5-yl)ethanol (68%, M-I-H+: 383);
2,2,2-TrifluoiO-l-naphthalen-l-yl-l-(l-o-tolyl-lH-indazol-5-yl)ethanol (71%, M+Η+: 433);
2,2,2-TrifluoiO-l-(4-fluoronaphthalen-l-yl)-l-(l-o-tolyl-lH-indazol-5-yl)ethanol (65%, M+Η+: 451); and
l-[3-(2,5-DimethylpyriOl-l-yl)phenyl]-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (70%, M-I-H+: 462).
Resolution to the (+)- and (-)enantiomers was accomplished by chiral HPLC on a CHIRALCEL™ AD-H column, eluting with 20% isopropanol-hexanes.
Example 3: 2,2,2-Trifluoro-l-isoquinolin-l-yl-l-(l -phenyl- lH-indazol-5-yl)ethanol
Figure imgf000124_0001
Step (a): In a 250 mL flask was placed l-phenyl-lH-indazole-5-carbaldehyde (4.0 g, 1 equiv.) in 80 mL of CH2Cl2. To this was added BF3OEt2 (2.5 mL, 1.1 equiv.) dropwise. After 5 minutes, 1,3-propanedithiol (1.9 mL, 1.1 equiv.) was added and the reaction allowed to stir for 18 hours at room temperature. The volatiles were removed and the residue was triturated with minimal acetonitrile and Filtered to provide the desired product 5-l,3-dithian-2-yl-l-phenyl-lH- indazole as a pale yellow solid (4.1 g, 72% yield; M+Η+: 313).
Step (b): In a 25 mL round bottom flask was placed 5-l,3-dithian-2-yl-l-phenyl-lH-indazole (83 mg, 1 equiv.) in 3 mL of TΗF under argon. This was cooled to -78°C where «-BuLi (2.5M in hexanes, 0.12 mL, 1.1 equiv.) was added dropwise. After 10 minutes, 2-chloroisoquinoline
(65 mg, 1.5 equiv.) was added as a solution in 1 mL of TΗF. The reaction was then allowed to warm to room temperature. After 20 minutes, the reaction was diluted with water and extracted with EtOAc. The combined organics were dried and evaporated in vacuo. The residue was purified by flash chromatography to provide desired product l-[2-(l-phenyl-lH-indazol-5-yl)- l,3-dithian-2-yl]isoquinoline as a yellow oil (113 mg, 96% yield; MH-H+: 440).
Step (c): In a 100 mL round bottom flask was placed l-[2-(l-phenyl-lH-indazol-5-yl)-l,3- dithian-2-yl]isoquinoline (113 mg, 1.0 equiv.), HgCl2 (139 mg, 2.0 equiv.), HgO (56 mg, 1.0 equiv.) in 5 mL of 10% aqueous MeOH. This was heated at reflux for 4 hours. The reaction was then diluted with EtOAc and the solids filtered. The solids were rinsed with EtOAc. The filtrate was transferred to a separatory funnel and diluted with saturated solutions of sodium bicarbonate, sodium chloride and EtOAc. The organic layer was removed and rinsed with brine. The combined organics were then dried, Filtered, and evaporated in vacuo. The residue purified by flash chromatography. The major fraction was collected and evaporated in vacuo to provide the desired product isoquinolin-l-yl-(l-phenyl-lH-indazol-5-yl)methanone as a white solid (54 mg 59% yield; M+ϊf: 350).
Step (d): In a 50 niL round bottom flask was placed isoquinolin-l-yl-(l-phenyl-lH-indazol-5- yl)methanone (54 mg, 1 equiv.) in 2 mL of TΗF. This was cooled to 0°C where trifluoromethyl trimethyl silane (38 μL, 1.6 equiv.) was added dropwise. After addition the reaction was allowed to stir at 00C for 30 minutes, where TBAF (1.0 M in TΗF, 0.23 mL, 1.5 equiv.) was added and the reaction allowed to stir at room temperature for 18 hours. The reaction was then diluted with water and extracted with EtOAc. The organic was dried, filtered, and evaporated in vacuo and the residue was purified by flash chromatography to provide the desired product 2,2,2-trifluoro-l-isoquinolin-l-yl-l-(l-phenyl-lH-indazol-5-yl)ethanol as a pale yellow solid (52 mg, 80% yield; M+Η+: 420).
The following example was synthesized following the procedure illustrated for Example 3 following steps b), c), and d) using the corresponding electrophile. The percent yield of the reaction and the M+Ff1" are indicated in parentheses.
2,2,2-Trifluoro-l -(I -phenyl- lH-indazol-5-yl)-l-quinolin-4-ylethanol (13%, M+Η+: 420).
Example 4: l,l,l-Trifluoro-3-phenyl-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol
Figure imgf000125_0001
Step (a): To a suspension of the trimethylsulfoxonium iodide (3.2 g, 14.5 mmol) in 9.0 mL of DMSO was added NaH (0.6 g, 14.5 mmol). The resulting solution was allowed to stir for 30 minutes at room temperature and under an atmosphere of argon. A solution of this ylide (4.5 mL) was added to a solution of 2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanone (2.0 g, 6.9 mmol) in 4.5 mL of DMSO and the resulting solution was allowed to stir at room temperature for 1.5 hours. The reaction mixture was poured onto 100 mL of water and extracted with three 75 mL portions of EtOAc. The combined organic layers were washed with 50 mL of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-85% hexanes/EtOAc). The desired product l-phenyl-5-(2-trifluoromethyloxiranyl)-lH- indazole was obtained as a white solid (0.8 g, 36% yield; M+Η+: 305).
Step (b): To a solution of l-phenyl-5-(2-trifiuoromethyloxiranyl)-lH-indazole (50.0 mg, 0.1 mmol) in 0.5 mL of TΗF was added phenylmagnesium bromide (1.0 M, 1.3 mL, 1.3 mmol) followed by stirring in a sealed reaction tube at 8O0C for 3 days. The reaction was quenched by the addition of 2.0 mL of saturated aqueous ammonium chloride solution, and 1 mL of water. The aqueous layer was extracted with three 5 mL portions of EtOAc and the combined organic layers were dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%- 85% hexanes/EtOAc). The desired product l,l,l-trifluoro-3-phenyl-2-(l-phenyl-lH-indazol-5- yl)propan-2-ol was obtained as a white solid (17 mg, 35.0% yield; M+Η1": 383).
Example 5: l,ljl-Trifluoro-3-(3-fluorophenyl)-2-(l-phenyl-lH-indazoI-5-yl)propan-2-ol;
Figure imgf000126_0001
To a solution of l-phenyl-5-(2-trifluoromethyloxiranyl)-lH-indazole (50.0 mg, 0.1 mmol) in 0.5 mL of TΗF was added 3-fluorophenylmagnesium bromide (1.0 M, 1.3 mL, 1.3 mmol). The reaction mixture was allowed to stir in a sealed reaction tube at 8O0C for 3 days. The reaction was quenched by the addition of 2.0 mL of saturated aqueous ammonium chloride solution, and 1 mL of water. The aqueous layer was extracted with three 5 mL portions of EtOAc and the combined organic layers were dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-85% hexanes/EtOAc). The desired product l,l,l-trifluoro-3-(3- fluoropheiiyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol was obtained as a white solid (17 mg, 32.0% yield; M+Η*: 401).
The following examples were synthesized following the procedure illustrated for Example 5. The percent yield of the reaction and the M+Η4 are indicated in parentheses.
3-(3-Chloro-2-fluorophenyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol (37%, MH-H+: 435);
3-(4-Chloro-3-fluorophenyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (29%, M+Η1": 435); and
3-(4-Chloro-2-fluorophenyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (33%, M+¥t: 435).
Example 6: l-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propyl]-li3r-indoIe-
3-carbonitrile
Figure imgf000127_0001
To a solution of l-phenyl-5-(2-trifluoromethyloxiranyl)-lH-indazole (50.0 mg, 0.1 mmol) in 0.5 mL of TΗF was added indole-3-carbonitrile (45.0 mg, 0.3 mmol) and sodium ethoxide (21% wt. in ethanol, 0.13 mL, 0.30 mmol). The resulting solution was allowed to stir in a sealed reaction tube at 9O0C for 12 hours. The reaction mixture was cooled to room temperature and 2.0 mL water of water was added. The aqueous layer was extracted with two 5 mL portions of ethyl ether. The organic layers were combined and washed with water and brine, then dried over sodium sulfate, and filtered. The solvents were removed by rotary evaporation in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 95%-90% hexanes/EtOAc). The desired product 1 -[3,3,3 -trifluoro-2- hydiOxy-2-(l-phenyl-lH-indazol-5-yl)propyl]-lH-indole-3-carbonitrile was obtained as a white solid (20 mg, 27% yield; M+Η+: 447).
The following examples were synthesized following the procedure illustrated for Example 5 using the corresponding amine reagents. The percent yield of the reactions and the M+H+ are indicated in parentheses.
l,l,l-Trifluoro-3-indol-l-yl-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (34%; M+Η+: 422);
3-(3,4-Dihydro-2H-quinoxalin- 1 -yl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (58%; M+Η+: 439);
3-(3,4-Dihydro-2H-quinolin-l -yl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (55%; M+Η+: 438); and
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-pyrrolo[2,3-c]pyridin- 1 -ylpropan-2-ol (17%; M+Η+: 423).
Example 7: 3-(3,5-Dimethoxyphenoxy)-l,l»l-trifluoro-2-(l-phenyl-lH-indazol-5- yl)propan-2-oI
Figure imgf000128_0001
A suspension of 2-/ert-butylimino-2-diethylamino-l,3-dimethylperhydro- 1,3,2- diazaphosphorine, polymer-bound (PS-BEMP) (20 mg, 0.040 mmol) in a solution of 1-phenyl- 5-(2-trifluoromethyloxiranyl)-lH-indazole (5 mg, 0.016 mmol) and 3,5-dimethoxyphenol (3 mg, 0.019 mmol) in TΗF, was shaken and heated to 60°C for 48 hours. The reaction was filtered to remove the resin and washed with TΗF. The combined solutions were evaporated in vacuo. The crude white solid was separated by preparative reverse phase ΗPLC to give the desired product 3 -(3 ,5-dimethoxyphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5- yl)propan-2-ol as a white solid (6 mg, 79% yield; MH-H+: 459).
The following examples were synthesized following the procedure illustrated for Example 7 using the corresponding phenol reagent and the corresponding epoxide. When applicable, the percent yield of the reaction and the M+H+ are indicated in parentheses.
l,l,l-TrifluoiO-3-ρhenoxy-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (78%; M-I-H+: 399);
3-(3,5-Difluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (68%;
M+Η+: 435);
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3 -(2-trifluoromethylphenoxy)propan-2-ol (M+Η+: 467);
3-(2-Chloro-3,5-difluorophenoxy)- 1,1,1 ~trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol (M+PT1-: 469);
3 -(5-Chloro-2-methylphenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η+: 447);
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol (M+Η*: 478);
l,l,l-Trifluoro-3-(indan-5-yloxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 439);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trichlorophenoxy)propan-2-ol (M-I-H+: 501);
l,l,l-Trifiuoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol (M+Η1": 441);
3-(3-Bromophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η4": 478); 3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 467);
3-(2-Bromophenoxy)-l,l,l-tπfluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 478);
1,1,1 -Trifluoro-2-(l -phenyl- IH- indazol-5-yl)-3-(3-trifluoiOmethylphenoxy)propan-2-ol (M+Η"1": 467);
3-(2-Chloro-5-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (MH-Pi+: 447);
1,1,1 -Trifluoro-2-( 1 -phenyl-1 H-indazol-5-yl)-3-(4-trifluoromethylphenoxy)propan-2-ol (M+Η+: 467);
1,1,1 -Trifluoro-3-(naphthalen-2-yloxy)-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η"1": 449);
3-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (MH-H+: 433);
3-(4-Chlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 433);
3-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η+: 447);
3-(4-Chloro-2-fluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η4": 451);
1,1,1 -Trifluoro-3-(4-fluoro-2-methylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η^l);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,3,4-trifluorophenoxy)propan-2-ol (M+Η+:
453); 3-(2-Chloro-3,5-difluoiOphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (MH-H+: 469);
l,l,l-Trifluoro-3-(7-methoxynaphthalen-2-yloxy)-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol (MH-H+: 479);
3-(2-Bromo-5-fluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- IH- indazol-5-yl)propan-2-ol (M+Η+: 496);
1,1,1 -Trifluoro-3 -(2-fluoro-5-trifluoromethylphenoxy)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2- ol (M-I-H+: 485);
3-(4-Bromo-3-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M-I-H+: 492);
1,1,1 -Trifluoro-3 -(2-fluoro-5-methylphenoxy)-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol (M+Η+: 431);
l,l,l-Trifluoro-3-(4-methylsulfanylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (MH-H+: 445);
3-(4-Bromophenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 478);
3-(3-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (MH-H+: 433);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-o-tolyloxypropan-2-ol (MH-H+: 413);
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-/w-tolyloxypropan-2-ol (M+Η+: 413);
l,l,l-Trlfluoro-2-(l-phenyl-lH-indazol-5-yl)-3-/?-tolyloxypropan-2-ol (MH-H+: 413); 3-(2,6-Dimethylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+rf": 427);
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η"1": 467);
3-(3,5-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 467);
l,l,l-Trifluoro-3-(naphthalen-l-yloxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 449);
l,l,l-TrifluoiO-3-(isoquinolin-7-yloxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+H+: 450);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2-trifluoromethoxyphenoxy)propan-2-ol (M+Η+: 483);
1,1,1 -Trifluoro-3-(4-phenylaminophenoxy)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol (JVM-H+: 490);
3 -(3 -Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (MH-H+: 447);
1,1,1 -Trifluoro-3-(3-fluoro-5-trifluoromethylphenoxy)-2-( 1 -phenyl- IH- indazol-5-yl)propan-2- ol (MHhH+: 485);
1,1,1 -Trifluoro-3-(2-methylsulfanylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η1": 445);
3-(4-Chloro-3-trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol (M+Η+: 501); 3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M-I-H+: 481);
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 481);
3 -Methoxy-4- [3 ,3 ,3 -trifluoro-2-hydroxy-2-( 1 -phenyl- lH-indazol-5-yl)propoxy]benzoic acid ethyl ester (M+Η+: 501);
1,1,1 -Trifluoro-3-(4-imidazol- 1 -ylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η1": 465);
3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)-l , 1 , 1 -trifluoro~2-(l -phenyl- IH- indazol-5- yl)propan-2-ol (M+Η+: 502);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 - yloxy)propan-2-ol (MH-H+: 411);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen-2- yloxy)propan-2-ol (M+Η+: 471);
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile (M+Η+: 441);
3-(2-BiOmophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+ET1": 496);
3-(2-Chlorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η+: 451);
3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (MB-H+ : 485); 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6-trichlorophenoxy)propan-2-ol (IVH-H+: 519);
3-(2-ChloiO-5-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]piOpan- 2-ol (M+Η1": 465);
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (MH-H+: 485);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-trifluoromethylphenoxy)propan-2- ol (M+Η4: 485);
1 ,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-o-tolyloxypropan-2-ol (M-HB+: 431);
3-(2,4-Dimethylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η+: 445);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6-trimethylphenoxy)propan-2-ol (MH-H+: 459);
3-(2,6-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]propan-2-ol (M-I-H+: 445);
3-{3,3,3-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile (M+Η+: 442);
3-(3-Bromophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]piOpan-2-ol (M+Η+: 496);
1,1,1 -Trifluoro-3-(3-fluorophenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M-I-H+: 435); 3-(3,5-Difluorophenoxy)- 1,1,1 -trifluoro~2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M-I-H+: 453);
3-(3-Chlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+Η^: 451);
3 -(3 ,5-Dichlorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol (MH-H+: 485);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-/«-tolyloxypropan-2-ol (M-I-H+: 431);
3-(3,5-Dimethylphenoxy)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η4: 445);
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile (M+Η+: 442);
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+Η+: 496);
1,1,1 -Trifluoro-3-(4-fluorophenoxy)-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M-I-H+: 435);
3-(4-Chlorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η+: 451);
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-trifluoromethylphenoxy)propan-2- ol (M-FH+: 485);
l,l,l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-p-tolyloxypropan-2-ol (M+rf": 431); 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(indan-5-yloxy)propan-2-ol (M+Η+: 457);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen-l -yloxy)propan-2-ol (M+Η+: 467);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen-2-yloxy)propan-2-ol (MH-H+: 467);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-5-yloxy)propan-2-ol (MH-H+: 468);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(quinolin-8-yloxy)propan-2-ol (MH-H+: 468);
3-(2,4-Difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (MH-H+: 453);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(quinolin-7-yloxy)propan-2-ol (M+Η+: 468);
3-Methoxy-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid ethyl ester (M+Η+: 519);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-phenylaminophenoxy)propan-2-ol (MH-H+: 508);
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}phenyl)butyramide (MH-H+: 502);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- trifluoromethylsulfanylphenoxy)propan-2-ol (MH-H+: 517); 5-Acetyl-2-{3,3,3-tπfluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropoxy}benzoic acid methyl ester (M+Η+: 517);
3-(2-Bromo-5-fluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol (M+Η+: 514);
l,l,l-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(2,3,4-trifluoiOphenoxy)propan-2-ol (M+Η+: 471);
3-(2,5-Difluorophenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (MMH+: 453);
3-(4-Chloro-3-trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol (M+Η+: 519);
3-(Acridin-4-yloxy)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+rf" : 518);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3-morpholin-4-ylphenoxy)propan-2- ol (M+Η1": 502);
2-Chloro-4-{3,3,3-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile (MM-H+: 476);
3-(4-Bromo-2-methylphenoxy)- 1 , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-
Figure imgf000137_0001
3-(3-Chloro-4-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol (MM-H+: 465); 3 -(5 -Chloro-2-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5 -yl]propan- 2-ol (MH-H+: 465);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-mdazol-5-yl]-3-(2,3,6-trifluorophenoxy)propan-2-ol (MH-H+: 471);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,5-trifluorophenoxy)proρan-2-ol (MH-H+: 471);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6-trifluorophenoxy)piOpan-2-ol (M+Η+: 471);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-fluoro-5- trifluoromethylphenoxy)propan-2-ol (MH-H+: 503);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-fluoro-5- trifluoromethylphenoxy)propan-2-ol (M+tf: 503);
3-(2-Chloro-4-methylphenoxy)-l,l,l-trifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol (M-I-H+: 465);
3-(4-Chloro-2-fluoiOphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]ρropan-2- ol (M+Η+: 469);
l,l,l-Trifluoro-3-(4-fluoro-2-methylphenoxy)-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol (MH-H+: 449);
1 ,1 , l-Trifluo1O-3-(2-fluoiO-6-methoxyphenoxy)-2-[l-(4-fluo1Ophenyl)- lH-indazol-5-yl]propan- 2-ol (MH-H+: 465);
3-(2-Chloro-3,5-difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol (M+Η4: 487); 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,5-trifluoiOphenoxy)propan-2-ol (M+Η+: 471);
4-{3,3,3-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}benzonitrile (M+Η+: 497);
3-(4-Bromo-3-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol (MH-H+: 510);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxynaphthalen-2- yloxy)propan-2-ol (JVU-H+: 497);
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazo 1-5- yl]propan-2-ol (M+Η+: 499);
4-{3,3,3-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropoxy}indan-l-one (M+Η^l);
5-Bromo-2-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile (M+Η1": 521);
1,1,1 -Trifluoro-3-(2-fluoro-5-methylphenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol (M-I-H+: 449);
5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile (M-I-H+: 476);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-trifluoromethoxyphenoxy)propan- 2-ol (M+Η1": 501); l,l,l-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(isoquinolin-7-yloxy)propan-2-ol (M+Η+: 468);
3 -(3,4-Dimethoxyphenoxy)- 1 , 1 , 1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+Η4": 477);
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- IH- indazol-5-yl]-3-(3-trifluoromethoxyphenoxy)propan- 2-ol (M+Η+: 501); and
3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5- yl]propan-2-ol (M+Η+: 499).
Example 8: l,l5l-Trifluoro-2-(l-phenyHJH-indazol-5-yI)-3-phenyIsulfanylpropan-2-ol
Figure imgf000140_0001
To a solution of l-phenyl-5-(2-trifluoromethyloxiranyl)-lH-indazole (50.0 mg, 0.2 mmol) in DMF (0.5 mL) was added benzenethiol (54.2 μL, 0.5 mmol) and the resulting mixture was heated to 1200C in a sealed tube for 14 hours. The reaction mixture was cooled to room temperature, diluted with 5 mL of EtOAc, washed with three 10 mL portions of water and a 10 mL portion of brine, dried over sodium sulfate, and filtered. The solvent was removed by rotary evaporation and the crude material was purified by flash column chromatography (eluted with 85% hexanes/EtOAc). The desired product 1, 1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)- 3-phenylsulfanylpropan-2-ol was obtained as a colorless oil (44 mg, 64% yield; MH-H+: 415).
Example 9: l,l5l-Trifluoro-3-(4-fluorophenylsulfanyI)-2-(l-phenyl-liϊ-indazol-5- yl)propan-2-ol
Figure imgf000141_0001
A suspension of l,5,7-triazabicyclo[4.4.0]dec-5-ene bound to polystyrene (PS-TBD) (52 mg, 0.134 mmol) in a solution of l-phenyl-5-(2-trifluoromethyloxiranyl)-lH-indazole (17 mg, 0.056 mmol) and 4-fluorobenzenethiol (9 mg, 0.070 mmol) in TΗF was shaken at room temperature for 12 hours. The resin was filtered and washed with TΗF. The combined solutions were concentrated in vacuo to give a white solid. The crude material was purified using mass-triggered RP-ΗPLC, and the desired product l,l,l-trifluoro-3-(4- fluorophenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol was obtained as a colorless oil (20 mg, 86% yield; M+BT1": 433).
The following examples were synthesized following the procedure illustrated for Example 9 using the corresponding thiophenol reagent and the corresponding epoxide. The M+Η* are indicated in parentheses.
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η1": 457);
1,1,1 -Trifiuoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol (M+Η+:
416);
3-(4-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; (M+Η+: 443);
4-Methyl-7-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-l- benzopyran-2-one (MMH+: 497);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan-2-ol (MH-H+: 483); 3-(2,3-DichloiOphenylsulfanyl)-l,l,l-trifluoiO-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η"1": 483);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylphenylsulfanyl)propan-2-ol (M+Η+: 483);
1,1,1 -Trifluoro-3 -(naphthalen- 1 -ylsulfanyl)-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol (IVU-H+: 465);
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3 -(4-thiophen-2-ylpyrimidin-2- ylsulfanyl)propan-2-ol (M+Η+: 499);
1 , 1 , 1 -TrifluoiO-2-( 1 -phenyl- 1 H- indazol-5-yl)-3-(4-phenylpyrimidin-2-ylsulfanyl)propan-2-ol (M+H+: 493);
3 - [4-(4-Chlorophenyl)pyrimidin-2-ylsulfany 1] -1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol (M+Η1": 527);
6-Methyl-2-[3,3,3-trifluoro-2-hydiOxy-2-(l-phenyl-lH-indazol-5-yl)piOpylsulfanyl]-4- trifluoromethylnicotinonitrile (IVB-H+: 523);
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(5-trifluoromethylpyridin-2-ylsulfanyl)propan- 2-ol (M+Η+: 484);
3-(2-ChloiO-4-fluorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 467);
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)-3-(4-trifluoromethoxyphenylsulfanyl)propan-2-ol (IVB-H+: 499);
3-(4-Bromo-2-trifluoromethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol (MB-H+: 578); 1,1,1 -Trifluoro-3-(4-methoxyphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η4": 445);
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(quinolin-2-ylsulfanyl)propan-2-ol (M+Η+: 466);
3 -(4-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)piOpan-2-ol (M+Η4: 449);
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(pyrimidin-2-ylsulfanyl)propan-2-ol (M+Η+: 417);
3 -(4,6-Dimethylpyrimidin-2-ylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2- 01 (^4+^: 445);
3 -(3 ,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 483);
3-(2,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-1 H-indazol-5-yl)propan-2-ol (M+Η÷: 483);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-4-ylsulfanyl)ρropan-2-ol (MR-H+:
416);
l,l,l-Trifluoro-3-(3-methoxyphenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (MH-H+: 445);
1,1,1 -Trifluoro-3-(2-methoxyphenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol (MR-H+: 445); 3-(3 -Chlorophenylsulfany I)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η+: 449);
3-(2,6-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol (MHhH+: 483);
3-(2,6-Dichlorophenylsulfanyl)- 1 , 1 , 1 -tπfluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 449);
3-(3-Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (IVB-H+: 494);
3-(3 ,4-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (MH-H+: 443);
l,l,l-Trifluoro-3-(naphthalen-2-ylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η1": 465);
1,1,1 -Trifluoro-3 -(2-fluorophenylsulfanyl)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol (M+BT1": 433);
1,1,1 -TrifluoiO-3-(3~fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 433);
3-(2,5-Dimethoxyphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 474);
3-(2,4-Dimethylphenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+tf": 443);
3-(2,5-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η4: 443); 3-(2,6-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η"": 443);
3-(2-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol (IVH-H+: 443);
2-[3,3,3-Trifluoro-2-hydiOxy-2-(l-phenyl-lH-indazol-5-yl)piOpylsulfanyl]benzoic acid methyl ester (M-I-H+: 473);
1 , 1 , l-Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4-trifluoromethylpyrimidin-2- ylsulfanyl)propan-2-ol (M-I-H+: 485);
3-(3,5-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol (M+Η+: 443);
3-(3,5-Bis-trifluoromethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan- 2-ol (M+Η+: 551);
3-(2,4-Difluorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M-^H+: 451);
1,1,1 -Trifluoro-3-(4-isopiOpylphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η1": 457);
3-(2,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5 -yl)propan-2-ol (M+Η+: 483);
3-(3,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 483); 1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2-trifluoromethylphenylsulfanyl)propan-2-ol (M+Η+: 483);
3-(3,4-Difluorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 483);
3-(3-Ethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 459);
3-(4-fert-Butylphenylsulfanyl)- 1 , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (M+Η+: 471);
N-{4-[3,3,3-Trifluoro-2-hydiOxy-2-(l -phenyl- lH-indazol-5- yl)propylsulfanyl]phenyl}acetamide (M+Η1": 472);
3 -(4-Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η+: 494);
1,1,1 -Trifluoro-3-(4-fluorophenylsulfanyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol (M+Η+: 433);
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (MH-H+: 457);
l,l,l-TrifluoiO-2-(l-phenyl-lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol (M+Η*: 416);
1,1,1 -Trifluoro-3-(4-nitrophenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η1": 460);
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-o-tolylsulfanylpropan-2-ol (M+Η+: 429); 1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-7?2-tolylsulfanylpropan-2-ol (M+Η+: 429);
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3:p-tolylsulfanylpropan-2-ol (M+Η+: 429);
3-(3-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol (M+Η1": 467);
3-(3,4-Dimethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (MHhH+: 475);
3-(5-teλt-Butyl-2-methylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)piOpan-2- ol (MH-H+: 485);
1,1,1 -Trifluoro-2-( 1 -phenyl- IH- indazol-5-yl)-3-(2,4,6-trimethylphenylsulfanyl)propan-2-ol (M+ΗT1": 457);
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan-2-ol (M+Η4: 483);
1,1,1 -TrifluoiO-3-(4-methylsulfanylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol (MH-H+: 461);
3-(2-Chloro-6-methylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)piOpan-2-ol (MH-H+: 463);
3-(2-fe?t-Butylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol (MH-H+: 471);
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylpyridin-2-ylsulfanyl)propan- 2-ol (MH-H+: 484); and 1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoiOmethoxyphenylsulfanyl)propan-2-ol (M+Η+: 499).
Example 10: l,l,l-Trifluoro-2-phenyl-3-(l-phenyl-lH-indazoI-5-yI)propan-2-ol
Figure imgf000148_0001
Step (a): In a 50 mL flask was placed l-trimethylsilyl-l,3-dithiane (4.0 equiv.) in 8 niL of TΗF. This solution was cooled to -78°C and w-BuLi (2.5 M in hexanes, 3.0 equiv.) was added dropwise. After addition, the reaction was warmed up to 0°C and allowed to stir for 15 minutes. At this time, the solution was cooled back to -78°C and a solution of 1-phenyl-lH- indazole-5-carbaldehyde (384 mg, 1 equiv.) in 4 mL of TΗF was added and the reaction was allowed to stir at -780C for 30 minutes. The reaction mixture was diluted with 20 mL of water and extracted with two 50 mL portions of EtOAc. The combined organics were dried over sodium sulfate, filtered, and evaporated in vacuo. The residue was purified by flash chromatography to provide 5-(l,3-dithian-2-ylidenemethyl)-l-phenyl-lH-indazole as a pale oil (91% yield, M+Η+: 325).
Step (b): In a 50 mL flask was placed 5-(l,3-dithian-2-ylidenemethyl)-l-phenyl-lH-indazole (511 mg, 1 equiv.) in 8 mL Of CH2Cl2. To this solution was added triethylsilane (0.8 mL, 3.2 equiv.) followed by trifluoroacetic acid (0.32 mL, 2.6 equiv.). This solution was allowed to stir at room temperature for 18 hours. To the reaction was slowly added 20 inL of saturated sodium bicarbonate solution. This was transferred into a separately funnel and extracted with two 50 mL portions of CH2Cl2. The organic fractions were dried, filtered, and evaporated in vacuo. The residue was adhered to silica and purified by flash chromatography to provide 5-(l,3- dithian-2-ylmethyl)-l -phenyl- 1 H- indazole as a pale yellow oil that solidified upon standing (437 mg, 85% yield; M+H*: 327).
Step (c): To a solution of 5-(l,3-dithian-2-ylmethyl)-l -phenyl- lH-indazole (437 mg, 1 equiv.) in 50 mL of acetonitrile and 15 mL of water was added methyl iodide (9.8 mL, 50 equiv.). The reaction was allowed to stir at room temperature. After 4 hours, the reaction was poured into a separatory funnel and diluted with 200 mL of CH2Cl2 and 100 mL of saturated sodium bicarbonate solution. The organic fractions were removed in vacuo and the aqueous extracted with CH2Cl2. The combined organic fractions were dried, Filtered, and evaporated in vacuo. The residue was purified by flash chromatography. The desired fractions were combined and evaporated in vacuo to provide (l-phenyl-lH-indazol-5-yl)acetaldehyde as a colorless oil (277 mg, 38% yield; M+Η+: 237).
Step (d): In a 20 mL vial at 00C was placed (l-phenyl-lH-indazol-5-yl)acetaldehyde (50 mg, 1.0 equiv.) in 2 mL of TΗF. To this was added phenyl magnesium bromide (1.0 M in TΗF, 0.64 mL, 3.0 equiv.) and the reaction was allowed to warm to room temperature overnight (18 hours). The reaction mixture was cooled to 0°C and quenched with 1 mL of saturated aqueous ammonium chloride solution. The aqueous layer was extracted with three 10 mL portions of EtOAc, and the organic layers were combined and dried over sodium sulfate, filtered, and the solvents were evaporated in vacuo. The crude material was purified by flash chromatography to provide l-phenyl-2-(l -phenyl- lH-indazol-5-yl)ethanol as a white solid (24 mg, 36% yield; ^4+1^: 315).
Step (e): In a 100 mL flask was placed l-phenyl-2-(l -phenyl- lH-indazol-5-yl)ethanol (143 mg, 1 equiv.) in 10 mL of CH2Cl2. To this solution was added Dess-Martin's periodonane (193 mg, 1 equiv.) and the reaction was allowed to stir at room temperature. After 30 minutes, the mixture was diluted with CH2Cl2 and rinsed with saturated sodium bicarbonate solution. The organics were dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography. The desired fractions were combined and evaporated in vacuo to provide 1- phenyl-2-(l-phenyl-lH-indazol-5-yl)ethanone as a white solid (124 mg, 87% yield; JVH-H+: 313).
Step (f): In a 100 mL flask was placed l-phenyl-2-(l -phenyl- lH-indazol-5-yl)ethanone (100 mg, 1 equiv.) in 5 mL of TΗF. This was cooled to O0C where trifluoromethyltrimethylsilane (0.08 mL, 1.6 equiv.) was added. After 30 minutes, the reaction was warmed to room temperature and tetrabutylammonium fluoride (TBAF) was added dropwise (0.51 mL, 1.6 equiv.). After 20 minutes, the reaction was diluted with MeOH and evaporated in vacuo. The residue was purified by flash chromatography to provide the desired product l,l,l-trifluoro-2- phenyl-3-(l-phenyl-lH-indazol-5-yl)propan-2-ol as a white solid (21 mg, 20% yield; M+Η4": 383).
Example 11: 2,2,2-Trifluoro-l-phenyl-l-(l-phenyl-lH-benzotriazol-5-yI)ethanol
Figure imgf000150_0001
Step (a): To a solution of the (4-chloro-3-nitrophenyl)phenylmethanone (1.9 g, 7.26 mmol) in DMF was added aniline (1.9 mL, 20.85 mmol) and Ηunig's base (3.64 mL, 20.91 mmol). The resulting light brown solution was heated to 100°C for 12 hours. The solution was cooled to room temperature and slowly poured over 100 mL of cold water to produce a precipitate. The product (3-nitro-4-phenylaminophenyl)phenylmethanone was collected by filtration, and then crystallized from ethanol as a yellow solid (5.0 g, 75% yield; 14+H+: 319).
Step (b): To a slurry of (3-nitro-4-phenylaminophenyl)phenylmethanone (1.0 g, 3.14 mmol) in 10 mL of EtOH and 6 mL of acetic acid was added iron powder (3.5 g, 62.84 mmol). The black mixture was heated to 90°C for 2 hours. The dark red solution was filtered through a pad of CELITE® filter aid, rinsed with EtOAc, and neutralized with a saturated sodium bicarbonate solution. The organic layer was washed with water, brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo to give the product (3-amino-4- phenylaminophenyl)phenylmethanone as a yellow solid which did not require purification (850 mg, 94% yield; MH-H+: 289).
Step (c): To a pre-cooled solution of (3-amino-4-phenylaminophenyl)phenylmethanone (400 mg, 1.39 mmol) in 28 mL of AcOH was added sodium nitrite (145 mg, 2.08 mmol) in portions over 10 minutes with stirring. After 30 minutes, ice water was added and the desired product phenyl-(l -phenyl- lH-benzotriazol-5-yl)methanone precipitated as a tan solid which was filtered and washed with water. The product was dried overnight to get as a tan solid which did not require purification (400 mg, 96% yield; M+Η4": 300).
Step (d): To a pre-cooled solution of phenyl-(l-phenyl-lH-benzotriazol-5-yl)methanone (80 mg, 0.27 mmol) at 00C in TΗF was added dropwise TMSCF3. The resulting light yellow solution was stirred at 0°C for 15 minutes, and then a solution of tetrabutylammonium fluoride (TBAF) in (IM in TΗF, 0.2 mL, 0.2 mmol) was added dropwise at 00C. The reaction mixture was allowed to stir at room temperature for 12 hours. The TΗF was evaporated in vacuo and the residual oil was dissolved in EtOAc then washed with water and brine. The crude material Λvas purified by flash column chromatography with silica gel (eluted with 95%-85% hexanes/EtOAc). The desired product 2,2,2-trifluoro-l-phenyl-l-(l-phenyl-lH-benzotriazol-5- yl)ethanol was obtained as a tan foam (32 mg, 32% yield; M+Η4": 370). 2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-benzotriazol-5-yl]-l -phenylethanol (59%, M+Η*: 389) was prepared starting with 4-fluoroaniline and following the procedure illustrated for Example 11 steps a), b), c), and d).
Example 12: 2,2,2-Trifluoro-l-phenyl-l-(l-phenyl-lH-benzimidazoI-5-yl)ethanol
Figure imgf000152_0001
Step (a): A solution of phenyl-(l-phenyl-lH-benzotriazol-5-yl)methanone (from Example 10) trimethyl orthoformate in methanol is heated to reflux. The reaction mixture is cooled to room temperature. The methanol is evaporated in vacuo and the desired phenyl-(l -phenyl- IH- benzimidazol-5-yl)methanone is purified by flash column chromatography on silica gel.
Step (b): To a pre-cooled solution of phenyl-(l-phenyl-lH-benzimidazol-5-yl)methanone at O0C in TΗF is added dropwise TMSCF3. The resulting light yellow solution is stirred at 0°C and a solution of tetrabutylammonium fluoride (TBAF) in is added dropwise at 00C. The reaction mixture is allowed to stir at room temperature. The TΗF is evaporated in vacuo and the residual oil is dissolved in EtOAc then washed with water and brine. The desired product 2,2,2-trifluoro-l-phenyl-l-(l-phenyl-lH-benzimidazol-5-yl)ethanol is purified by flash column chromatography with silica gel.
Example 13: CycIopropylphenyl-(l-phenyl-lJfiT-indazol-5-yI)methanol
Figure imgf000153_0001
13
Step (a): To a solution of 1 -phenyl- lH-indazole-5-carbonitrile (1.23 g, 5.6 mmol) in 20.0 niL of TΗF at -78°C was added cyclopropylmagnesium bromide (33.7 niL, 0.5 M). The solution was allowed to warm up to room temperature then stirred for 14 hours. The reaction was cooled to 00C and then quenched by the addition of 20.0 mL of saturated aqueous ammonium chloride solution. The aqueous layer was extracted with three 30 mL portions of EtOAc, and the combined organic layer was washed with water, brine, dried over sodium sulfate, filtered, and the solvents were evaporated in vacuo. The desired product cyclopropyl-(l -phenyl- lH-indazol- 5-yl)methanone was obtained as a yellow oil following chromatography with EtOAc/hexanes (15%) (1.22 g, 83% yield; M+Η+: 263).
Step (b): To a solution of cyclopropyl-(l-phenyl-lH-indazol-5-yl)methanone (0.05 g, 0.19 mmol) in TΗF (0.5 mL) at 0°C, was added phenylmagnesium bromide (IM in TΗF, 0.67 mL, 0.67 mmol). The resulting solution was allowed to stir at room temperature for 12 hours. The reaction mixture was cooled to 0°C and quenched with 1 mL of saturated aqueous ammonium chloride solution. The aqueous layer was extracted with three 10 mL portions of EtOAc, and the organic layers were combined and dried over sodium sulfate, filtered and the solvents were evaporated in vacuo. The desired product cyclopropylphenyl-(l-phenyl-lH-indazol-5- yl)methanol was obtained as a white foam following column chromatography with silica gel (eluting with EtOAc/hexanes (15%) (50 mg, 65% yield; M+Η"1": 341)).
The following examples were synthesized following the procedure illustrated for Example 6 step b) using the corresponding Grignard reagents. The percent yield of the reactions and the M+Η+ are indicated in parentheses.
Cyclopropyl-(3,5-dichlorophenyl)-(l-phenyl-lH-indazol-5-yl)methanol (32%, M+Η+: 410); l-Cyclopropyl-2-(3,5-dichloroρhenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (50%, MH-H+: 424);
1-Cyclopropyl-l -(I -phenyl- lH-indazol-5-yl)-2-rø-tolylethanol (31%, M+Η+: 369); and
l-Cycloproρyl-l-(l-phenyl-lH-indazol-5-yl)-2-p-tolylethanol (28%, M+Η+: 369).
Example 14: 2-Phenyl-l-(l-phenyl-lH-indazol-5-yI)propan-2-ol
Figure imgf000154_0001
Step (a): To a solution of l-phenyl-2-(l-phenyl-lH-indazol-5-yl)ethanone in TΗF is added a solution of methylmagnesium bromide in TΗF (1.2 equiv.). The reaction mixture is cooled to 0°C and quenched with 1 mL of saturated aqueous ammonium chloride solution. The aqueous layer is extracted with EtOAc and the organic layers are combined and dried over sodium sulfate, filtered, and the solvents are evaporated in vacuo. The crude material is purified by flash chromatography to provide the desired product 2-phenyl-l-(l-phenyl~lH-indazol-5- yl)propan-2-ol.
Example 15: l-Cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yI]-2-phenylaminoethanol
Figure imgf000154_0002
Step (a): To a suspension of the trimethylsulfoxonium iodide in DMSO is added NaH (1.05 equiv.). The resulting solution is allowed to stir at room temperature under an atmosphere of argon. A solution of this ylide is added to a solution of cyclopropyl-[l-(4-fluorophenyl)-lH- indazol-5-yl]methanone (0.9 equiv.) in DMSO and the resulting solution is allowed to stir at room temperature. The reaction mixture is poured onto water and extracted with EtOAc. The combined organic layers are washed with brine, dried over sodium sulfate, filtered, and the solvent is evaporated in vacuo. The crude material is purified by flash column chromatography to obtain the desired product 5-(2-cyclopropyloxiranyl)-l-(4-fluorophenyl)-lH-indazole.
Step (b): To a solution of aniline in DMF is added NaH (1 equiv.). To this solution is added 5- (2-cyclopropyloxiranyl)-l-(4-fluorophenyl)-lH-indazole. The resulting solution is heated to 80°C. The reaction mixture is cooled to room temperature and then quenched with a saturated solution of ammonium chloride. Ethyl acetate is added and the organic layer is washed with brine, dried over magnesium sulfate, and filtered. The solvent is evaporated in vacuo, and the crude material is purified by flash column chromatography to obtain the desired product 1- cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-phenylaminoethanol.
Example 16: l-Cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazoI-5-yl]-2- phenylsulfanylethanol
Figure imgf000155_0001
A solution of thiophenol and 5-(2-cyclopropyloxiranyl)-l-(4-fluorophenyl)-lH-indazole in DMF is heated to 8O0C. The reaction mixture is cooled to room temperature and then quenched with a saturated solution of ammonium chloride. Ethyl acetate is added and the organic layer is washed with brine, dried over magnesium sulfate, and filtered. The solvent is evaporated in vacuo, and the crude material is purified by flash column chromatography to obtain the desired product l-cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-phenylsulfanylethanol.
Example 17: l-Cyclopropyl-2-(3,5-difluorophenoxy)-l-[l-(4-fluorophenyl)-lH-indazoI-5- yljethanol
Figure imgf000156_0001
A suspension of l,5,7-triazabicyclo[4.4.0]dec-5-ene bound to polystyrene (PS-TBD) (52 mg, 0.134 mmol) in a solution of 5-(2-cyclopropyloxiranyl)-l-(4-fluorophenyl)-lH-indazole (0.5 equiv) and 3,5-difluorophenol (1.0 equiv.) in TΗF is shaken at room temperature. The resin is filtered and washed with TΗF. The combined solutions are concentrated in vacuo and the crude material is purified by flash column chromatography to obtain the desired product cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-phenylsulfanylethanol.
Example 18: CycIopropylphenyl-(l-phenyl-lJΗr-benzotriazoI-5-yl)methanol
Figure imgf000156_0002
To a solution of phenyl-(l-phenyl-lH-benzotriazol-5-yl)methanone (70 mg, 0.23 mmol) in TΗF was added cyclopropyl magnesium bromide (0.5 M in TΗF, 0.8 mL, 0.40 mmol). The resulting brown solution was stirred at room temperature for 6 hours. The reaction was quenched with 2 mL of saturated aqueous ammonium chloride solution, diluted with EtOAc, and extracted. The organic layer was washed with water and brine, dried over magnesium sulfate (MgSO4), then filtered and evaporated in vacuo. The crude material was purified by flash column chromatography (eluted with 95%-85% hexanes/EtOAc) to get the desired product cyclopropylphenyl-(l-phenyl-lH-benzotriazol-5-yl)methanol as an off white solid (33 mg, 41%, M+Η+: 342).
Example 19: Cyclopropyl-[l-(4-fluorophenyl)-lH-benzotriazoI-5-yl]phenylmethanol
Figure imgf000157_0001
To a solution [l-(4-fluoiOphenyl)-lH-benzotriazol-5-yl]phenylmethanone (107 mg, 0.34 mmol) in TΗF was added cyclopropyl magnesium bromide (0.5 M in TΗF, 1.5 mL, 0.75 mmol). The resulting brown solution was stirred at room temperature for 6 hours. The reaction was quenched with 2 mL of saturated aqueous ammonium chloride solution, diluted with EtOAc, and extracted. The organic layer was washed with water and brine, dried over magnesium sulfate, then filtered and evaporated in vacuo. The crude material was purified by flash column chromatography (eluted with 95%-85% hexanes/EtOAc) to get the desired product cyclopropyl-[l-(4-fluorophenyl)-lH-benzotriazol-5-yl]phenylmethanol as an off white solid (70 mg, 57%, MH-H+: 360).
Example 20: Cyclopropylphenyl-(l-phenyl-lH-indol-5-yI)methanol
Figure imgf000157_0002
Step (a): To a solution of 1 -phenyl- IH- indole-5-carbonitrile in TΗF at -780C is added cyclopropylmagnesium bromide (1.2 equiv.). The solution is allowed to warm up to room temperature. The reaction is cooled to O0C and then quenched by the addition of saturated aqueous ammonium chloride solution. The aqueous layer is extracted with EtOAc and the combined organic layer is washed with water, brine, dried over sodium sulfate, filtered, and the solvents are evaporated in vacuo. The desired product cyclopropyl-(l -phenyl- lH-indol-5- yl)methanone is obtained following purification by column chromatography.
Step (b): To a solution of cyclopropyl-(l -phenyl- IH- indol-5-yl)methanone in TΗF at 00C is added phenylmagnesium bromide (1.3 equiv.). The resulting solution is allowed to stir at room temperature. The reaction mixture is cooled to O0C and quenched with saturated aqueous ammonium chloride solution. The aqueous layer is extracted with EtOAc and the organic layers are combined and dried over sodium sulfate, filtered, and the solvents are evaporated in vacuo. The desired product cyclopropylphenyl-(l-phenyl-lH-indol-5-yl)methanol is obtained following column chromatography with silica gel.
Example 21: l,ljl-Trifluoro-2-[l-(4-fluoiOphenyI)-lH-indazoI-5-yl]-3-indol-l-yIpropan-2- ol
Figure imgf000158_0001
A solution of l-(4-fluorophenyl)-5-(2-trifluoiOmethyloxiranyl)-lH-indazole (24 mg, 0.075 mmol) in 500 μL DMSO was added to the indoles (0.090 mmol). The mixture was shaken for 15 minutes to solubilize the indole, then a solution of sodium hexamethyldisilazide (NaΗMDS) (90 μL of a IM solution in TΗF, 0.090 mmol) was added and the resultant mixtures were shaken at room temperature for 16 hours. The reaction was then quenched with the addition of 50 μL of water, then after shaking for 30 minutes, the mixture was filtered through CELITE® filter aid. The reaction vial was rinsed with two 300 μL portions of DMSO and was passed through the CELITE® filter aid. Finally the CELITE® filter cakes was washed with two 200 μL portions of DMSO. The combined solutions were evaporated in vacuo. The crude product was purified by preparative reverse phase ΗPLC to give the desired product (M+H1": 440).
The following examples were synthesized following the procedure illustrated for Example 21 using the corresponding indole reagent and the corresponding epoxide. The M+Η* is indicated in parentheses.
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-3-(4-methylindol- 1 -yl)propan-2-ol (M+Η+: 454); 3-[2-(4-Chlorophenyl)indol- 1 -yl]- 1 ,1,1 -trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5- yl]propan-2-ol (M+Η*: 550);
(l-{3,3,3-TrifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)acetonitrile (M+Η+: 479);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxyindol- 1 -yl)propan-2-ol (M+Η+: 470);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5-yl]-3-(5-methylindol- 1 -yl)propan-2-ol (M+Η+: 454);
3-(4-Benzyloxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M-I-H+: 546);
3-(4-Chloroindol- 1 -yl)- 1 ,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (MH-H+: 474);
3 -(6-Chloroindol- 1 -yl)- 1 ,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M-I-H+: 474);
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methylindol- 1 -yl)propan-2-ol (M+Η+: 454);
l-{3,3,3-TrifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-4- carboxylic acid methyl ester (M+Η+: 498);
1,1,1 -Trifluoro-3 -(6-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol (M+Η+: 458); l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-3- carboxylic acid methyl ester (M+Η*: 498);
2,2,2-Trifluoro-l-(l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydiOxypropyl}-lH-indol-3-yl)ethanone (M+Η+: 536);
l,l,l-TrifluoiO-3-(4-fluoroindol-l-yl)-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]propan-2-ol (M+Η+: 458);
N-[2-(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indol-3-yl)ethyl]acetamide (M+K1": 555);
3-(7-Bromoindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η+: 519);
3-(7-ChloroindoI-l-yI)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η*: 474);
(2-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3-yl)acetic acid ethyl ester (M+Η1": 540);
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indole-5- carboxylic acid methyl ester (IVH-H+: 498);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-methyl-5-nitroindol-l -yl)propan- 2-ol (M+Η*: 499);
l,l,l-Trifluoro-2-[l-(4-fluoroρhenyl)-lH-indazol-5-yl]-3-[2-(4-fluorophenyl)indol-l- yl]propan-2-ol (M+Η4: 534);
3-(4-Bromoindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ρropan-2-ol (M+ϊt: 519); 3-(6-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+ET1": 519);
3-(3-Dimethylaminomethyl-6-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η1": 527);
(5-Methoxy- 1 - { 3 ,3 ,3 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]-2-hydroxypropyl } - 1 H- indol-3-yl)acetonitrile (M+Η+: 509);
(5-Benzyloxy- 1 - { 3 ,3 ,3 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]-2-hydroxypropyl} - IH- indol-3-yl)acetonitrile (M+Η+: 585);
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-6- carboxylic acid methyl ester (M+ΗT1": 498);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-nitroindol- 1 -yl)propan-2-ol (MR-H+: 485);
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-4- carbonitrile (MMH+: 465);
3-(5-Benzyloxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η"": 546);
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indole-5- carbonitrile (M+U1": 465);
3-(3-Dimethylaminomethyl-5-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η4": 527); 1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(5 -methoxy-2-methylindol- 1 - yl)propan-2-ol (M+Η4": 484);
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5 -yl]-3 -(2-methylindol- 1 -yl)propan-2-ol (M+Η+: 454);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(3-methylindol- 1 -yl)propan-2-ol (M+Η"1": 454);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(7-methylindol- 1 -yl)propan-2-ol (M+Η4: 454);
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- IH- indazol-5-yl]-3-(5-nitroindol- 1 -yl)propan-2-ol (M+Η1": 485);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-phenylindol- 1 -yl)propan-2-ol (M+Η^lδ);
(2-Phenyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3-yl)acetonitrile (M+Η+: 554);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-pyrrolo[2,3-c]pyπdin-l-ylpropan-2- ol (M+Η÷: 441);
3-(7-Ethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+Η+: 468);
3-(2,3-Dimethyl-5-nitroindol- 1 -yl)- 1 , 1 , 1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol (M+Η+: 513);
l,l,l-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(6-trifluoromethylindol-l-yl)propan- 2-ol (M+Η1: 508); 1,1,1 -Trifluoro-3-(7~fluoroindol- 1 -yl)-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (MH-H+: 458);
l-{3,3,3-TrifluoiO-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}-lH-indole-6- carbonitrile (MH-H+: 465);
1,1,1 -TrifIuoκ)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-indol- 1 -ylρroρan-2-ol (MH-H+: 440);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-pyrrolo[2,3-ό]pyridin- 1 -ylpropan-2- ol (M+ϊf: 441);
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-2- carboxylic acid ethyl ester (M+Η+: 512);
3-(2,3-Dimethylindol-l -yl)- 1 , 1 , l-trifluoiO-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (MH-H+: 468);
l-{3,3,3-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole-3- carbonitrile (MH-H+: 465);
l-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)ethanone (MH-H+: 482);
3-(3-Dimethylaminomethylindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol (MH-H+: 497);
3-(3-Dimethylaminomethyl-5-methoxyindol- 1 -yl)- 1 , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (MH-H+: 527);
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol-3- yl)acetic acid ethyl ester (M-I-H+: 526); 2-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}-lH-indol-3- yl)acetamide (M+Η"1": 497);
3-(5-Bromoindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+Η+: 519);
1,1,1 -Trifluoro-3-(5-fluoroindol-l -yl)-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η"1": 458);
3-(5-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+Η1": 474);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-methoxyindol-l-yl)propan-2-ol (M+Η1": 470);
3-(5,6-Dimethoxymdol-l-yl)-l,l,l-trifluoiO-2-[l-(4-fluoropheiiyl)-lH-mdazol-5-yl]propan-2-ol (M+Η"": 500);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-nitroindol- 1 -yl)propan-2-ol (M+Η+: 485); and
5-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indole-2-carboxylic acid ethyl ester (M+Η1": 485).
Example 22: l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3- phenylaminopropan-2-ol
Figure imgf000165_0001
A solution of l-(4-fluorophenyl)-5-(2-trifluoromethyloxiranyl)-lH-indazole (24 mg, 0.075 mmol) in 500 μL of MeOH was added to the aniline (0.090 mmol). The mixture was heated at 5O0C for 16 hours. The solution was evaporated in vacuo. The crude products was purified by preparative reverse phase ΗPLC to give the desired product (M+Η4": 416).
The following examples were synthesized following the procedure illustrated for Example 22 using the corresponding aniline reagent and the corresponding epoxide. The M+Η1" is indicated in parentheses.
6- { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-2-hydroxypropylamino } -3H- isobenzofuran-1-one (M+Η*: 472);
N-(4-{3,3,3-TrifluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-2- hydroxypiOpylamino}phenyl)acetamide (MH-H+: 473);
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(indan-5-ylamino)propan-2-ol (M+Η1": 456);
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(indan-4-ylamino)propan-2-ol (M+Η+: 456);
3-(3-Bromophenylamino)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η+: 495); 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-o-tolylaminopropan-2-ol (M+Η1": 430);
3-(4-Chlorophenylamino)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η*: 450);
l,l,l-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-777-tolylaminopropan-2-ol (M+Η+: 430);
3-(4-Chloronaphthalen- 1 -ylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol (U+ϊt: 500);
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(6-methoxypyridin-3- ylamino)propan-2-ol (M+Η1": 447);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 - ylamino)propan-2-ol (M+Η"1": 470);
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-methoxyphenylamino)propan-2-ol (M+Η*: 446);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3-methoxyphenylamino)propan-2-ol (M+Η+: 446);
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-methoxyphenylamino)propan-2-ol (IVH-H+: 446);
3-(3-Chlorophenylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (M+tf: 450);
3-(5-Chloro-2-methylphenylamino)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol (IVR-H+: 464); 3-(2,6-Dimethylphenylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol (M+tf: 444);
1,1,1 -Trifluoro-3-(4-fluorophenylamino)-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol (M+Η+: 434);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- methylsulfanylphenylamino)propan-2-ol (M-I-H+: 462);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(naphthalen-2-ylamino)piOpan-2-ol (M+Η+: 466);
l,l,l-Trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-3-(2-methylquinolin-8-ylamino)propan- 2-ol (MH-H+: 481);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(methylphenylamino)propan-2-ol (MH-H+: 430);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-[(4- methoxyphenyl)methylamino]propan-2-ol (MH-H+ : 460);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl] -3 -(naphthalen-1 -ylamino)propan-2-ol (M+BT1": 466);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5-yl]-3-(4-morpholin-4- ylphenylamino)propan-2-ol (M+Η+: 501);
3 -(2,3-Dihydro- 1 ,4-benzodioxin-6-ylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]propan-2-ol (MH-H+: 474); 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6-trifluorophenylamino)propan- 2-ol (M+Η+: 470);
3-(Biphenyl-2-ylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η+: 492);
3-(2,4-Dimethylphenylamino)-l,l,l-tπfluoiO-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]propan-2- ol (M+Η+: 444);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6-trimethylphenylamino)propan- 2-ol (M+Η"1": 444);
3-(2,6-Dimethylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]propan-2- ol (M+Η+: 444);
3-(2-Ethyl-6-methylphenylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol (M-I-H+: 458);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3- methylsulfanylphenylamino)propan-2-ol (M+ET1": 462);
3-(3,5-Dimethylphenylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol (MH-H+: 444);
3 -(4-Chlorophenylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol (M+Η+: 450);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-phenoxyphenylamino)propan-2-ol (M+Η÷: 508);
3-(2,4-Dimethoxyphenylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan- 2-ol (M+Η+: 476); 3-(3,5-Dimethoxyphenylamino)-l5l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-mdazol-5-yl]propan- 2-ol (M+Η1": 476);
3-(4,5-Dimethoxy-2~methylphenylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5 - yl]propan-2-ol (M+Η+: 490);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3- trifluoromethoxyphenylamino)propan-2-ol (MH-H+: 500);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol~5-yl]-3-(2-methoxy-5- trifluoromethylphenylamino)propan-2-ol (M+Η*: 514);
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-methoxy-3- trifluoromethylphenylamino)propan-2-ol (M+Η+: 514);
3-(Biphenyl-3-ylamino)-l , 1 , 1 -trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol (M+Η*: 492);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5-yl] -3 -(4-ρiperidin- 1 - ylphenylamino)propan-2-ol (M+Η+: 499);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3-oxazol-5-ylphenylamino)propan- 2-ol (M+tf: 483);
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4-pyridin-4- ylmethylphenylamino)propan-2-ol (M+Η^: 507);
3-(4-ChIoro-2,6-dimethylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]prøpan-2-ol (M+Η+: 478); 1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-3 -(2-methylnaphthalen- 1 - ylamino)propan-2-ol (M+Ff1": 480);
3-(Biphenyl-4-ylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol (MH-H+: 492); and
5- { 3 ,3,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -2-hydroxypropylamino } - 1 ,3- dihydrobenzimidazol-2-one (M+Ff1": 472).
Example 23: l-(l-AIIyI-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyI)-lH-indazol-5- yljethanol
Figure imgf000170_0001
/-78°C -780C
Figure imgf000170_0002
Figure imgf000170_0003
Step (a): In a 100 niL flask was placed 3.0 g (25.7 mmol, 1 equiv.) of indole in 15 mL of DMF. This was cooled to O0C where 1.5 g (38.4 mmol, 1.5 equiv.) of a 65% suspension of sodium hydride in mineral oil was added in portions. After gas evolution (30 minutes), allyl bromide (2.4 mL, 28.2 mmol, 1.1 equiv.) was added and the reaction allowed to warm to room temperature. After 30 minutes, the reaction was poured into 300 mL of water and extracted with diethyl ether (Et2O). The combined diethyl ether extracts were dried, filtered, and evaporated in vacuo and used in the next step without further purification.
Step (b): In a 100 mL flask was placed 4 g of crude 1-allylindole in 30 mL of DMF. This was cooled to O0C where trifluoroacetic anhydride (5.7 mL, 40.7 mmol) was added and the reaction allowed to stir at room temperature. After 30 minutes, the reaction was poured into a separatory funnel and diluted with diethyl ether. The organic was separated and rinsed with two portions of brine and saturated sodium bicarbonate solution. The organic was dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography (0-5% EtOAc-hexanes) to provide 5.54 g of the desired product as a yellow oil (86%, MH-H+ : 254).
Step (c): In a 50 mL flask under argon was placed l-(l-allyl-lH-indol-3-yl)-2,2,2- trifluoroethanone (747 mg, 2.6 mmol, 1.3 equiv.) in 10 mL of TΗF. This was cooled to -780C. In a separate vial was placed l-allyl-3-trifluoromethylcarbonyl indole (500 mg, 2.0 mmol, 1 equiv.) in 5 mL of TΗF and was cooled to -780C. At this point, W-BuLi (0.87 mL, 2.2 mmol, 1.1 equiv., 2.5 M in hexanes) was added quickly and dropwise to the flask containing bromoindazole (prepared according to a procedure reported by Bamborough et al. (WO 2005/073189, which is hereby incorporated by reference). After addition, the solution containing indole was added in one portion. After 5 minutes, the reaction was quenched with 5 mL of water and brought to room temperature. This was diluted with EtOAc and rinsed with water/brine. The organic was dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc/hexanes) to provide 813 mg of the desired product as a pale yellow foam (88%, M+Η1": 466).
The following examples were synthesized following the procedure illustrated for Example 23 step (c), using the corresponding bromoindazoles and suitably functionalized (indol-3-yl)-2,2,2- trifluoroethanone. The % yield and M+Η+ are indicated in parentheses.
l-(7-Bromo-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol (44%, M+Η1": 519);
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester (48%; M+Η*: 498);
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -( 1 -methyl-7-nitro- lH-indol-3- yl)ethanol (23%, MH-H+: 485); l-Cl-Allyl-lH-indol-S-yO^^^-trifluoiO-l-Cl-p-tolyl-lH-indazol-S-yOethanol (60%, M+Η4 462);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l -(I -methyl- lH-indol-3-yl)ethanol (11%, M+Η+: 44O);
l-(6-Bromo-l-methyl-lH-indol-3-yl)-2,2,2-tπfluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol (15%, M+Η"1": 519);
1 -Methyl-3 - {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxyethyl } - 1 H- indole-6-carbonitrile (7%, M+Η+: 465);
1 -Benzyl-3 - {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxyethyl } - 1 H- indole-7-carboxylic acid methyl ester (53%, M+Η"1": 574); and
1 -[6-Bromo- 1 -(4-methoxybenzyl)- lH-indol-3-yl]-2,2,2-trifluoiO- 1 -[I -(4-fluorophenyl)- IH- indazol-5-yl]ethanol (31%, M+Η+: 625).
Example 24: 2-(3-{2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-mdazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide
Figure imgf000172_0001
G) KMnO4 acetone/water 3:1
Figure imgf000172_0002
Step (a): In a 50 niL flask was placed l-(l-allyl-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol (250 mg, 0.54 mmol, 1 equiv.) in 10 mL of acetone/water (3:1). This was cooled to O0C where potassium permanganate (KMnO4; 94 mg, 0.59 mmol, 1.1 equiv.) was added as a solution in 10 mL of acetone/water (3:1) dropwise. The ice bath was then removed and the reaction allowed to stir at room temperature for 2 hours. The reaction was filtered and the volatiles were removed. The residue was then partitioned between water and EtOAc. The organics were dried, filtered, and evaporated in vacuo. The residue dissolved in minimal DMF and purified by ΗPLC (5-100% CΗ3CN/water/0.1% TFA) to provide 218 mg of the desired product 3-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]-l-hydroxyethyl}indol-l-yl)propane-l,2-diol as a white solid (80%, M+Η+: 500).
Step (b): In a 50 mL flask was placed the diol (350 mg, 0.70 mmol, 1 equiv.) in 6 mL of acetone and 2 mL of water. To this was added sodium periodate (172 mg, 0.77 mmol, 1.1 equiv.) and the reaction allowed to stir at room temperature for 72 hours. The solids were filtered and rinsed with acetone. The volatiles were then removed and the mixture was then transferred to a separatory funnel, basified with saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo to provide 319 mg of the desired product as white foam (97%, M+H+: 468).
Step (c): In a 100 mL flask was placed the aldehyde (269 mg, 0.58 mmol, 1 equiv.) in 9 mL of 3:1 acetone: water. Potassium permanganate (100 mg, 0.63 mmol, 1.1 equiv.) was added and the reaction allowed to stir at room temperature for 2 hours. The solids were filtered and rinsed with acetone. The volatiles were removed and the aqueous transferred to a separatory funnel. The aqueous was extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo to provide 261 mg of the desired acid as a tan solid (94%, M+H4": 484).
Step (d): In a 7 mL vial was placed the carboxylic acid (40 mg, 0.083 mmol, 1 equiv.) in 1 mL of DMF. To this was added triethylamine (63 μL, 0.5 mmol, 6 equiv.) followed by benzotriazol-l-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP; (56 mg, 0.11 mmol, 1.3 equiv.). After 5 minutes, ammonium chloride (44 mg, 0.83 mmol, 10 equiv.) was added, the reaction was capped, and the reaction allowed stirring at room temperature for 18 hours. The mixture was filtered into a vial and purified by HPLC (5-90% CH3CN/water/0.1% TFA). The desired fractions were combined and the CH3CN was removed. The organic was then extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo to provide 20 mg of the desired product as a white solid (50%, MH-H+: 483).
The following examples were synthesized following the procedure illustrated for Example 24 using the corresponding amines and suitably functionalized (indol-l-yl)acetic acid. The % yield and M+H4" are indicated in parentheses.
N-Methyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol- 1 -yl)acetamide (46%, M-I-H+: 497);
N-Cyanomethyl-2-(3-{2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide (49%, M+Η+: 522);
N-Carbamoylmethyl-2-(3-{2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-l - hydroxyethyl}indol-l-yl)acetamide (50%, M+Η+: 540);
1 -Morpholin-4-yl-2-(3- {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 - hydroxyethyl}indol-l-yl)ethanone (44%, M+Η+: 553);
N-Carbamoylmethyl-N-methyl-2- {3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5- yl)ethyl]indol-l-yl}acetamide (44%, IVM-H+: 550);
N-Carbamoylmethyl-2- {3 -[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- 1 H-indazol-5-yl)ethyl] indol- l-yl}acetamide (40%, M+Η+: 536);
N-(2-Methoxyethyl)-N-methyl-2- { 3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- 1 H-indazol-5- yl)ethyl]indol-l-yl}acetamide (50%, M+Η+: 551);
N-(2-Methoxyethyl)-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-j!7-tolyl-lH-indazol-5-yl)ethyl]indol- l-yl}acetamide (49%, M+Η+: 537); N-Cyanomethyl^-IS-p^^-trifluoro-l-hydroxy-l-Cl-^-tolyl-lH-indazol-S-yOethy^indol-l- yl}acetamide (37%, M+Η+: 518);
N-Methyl-2-{3-[2,2,2-trifluoro- 1 -hydroxy- 1 -(I -p-to\y\- lH-indazol-5-yl)ethyl]indol- 1 - yl}acetamide (39%, M+Η+: 493); and
2- { 3 -[2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethyl] indol- 1 -yl } acetamide (35%, M+Η4: 479).
Example 25: 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazoI-5-yl]-l-(lH-indol-3- yl)ethanol
Figure imgf000175_0001
To a stirred solution of indole (0.037 g, 0.320 mmol) in 4 niL of tert-butyl methyl ether at room temperature was added a solution of ethyl magnesium bromide (3M in diethyl ether, 0.200 mL, 0.600 mmol). The resulting dark grey solution was stirred at room temperature for 45 minutes, then copper iodide (0.032 g, 0.170 mmol) was added. The reaction mixture was stirred at room temperature for 45 minutes. A solution of the ketone in tert-butyl methyl ether (0.100 g, 0.324 mmol in 2.0 mL of /e?t-butyl methyl ether) was added to the reaction mixture at room temperature, and the reaction was allowed to be stirred at for 2 hours at room temperature. 2.0 mL of ice-cold water was added to the reaction, and the reaction was stirred at room temperature for 10 minutes. The reaction mixture was added to 10 mL of dichloromethane and the resulting dark precipitate was filtered through a pad of CELITE® filter aid. The dichloromethane phase was washed with a 5 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 80% hexanes/EtOAc). The desired product was obtained as a light yellow solid (37% yield, M+Η: 426). The following examples were synthesized following the procedure illustrated for Example 25 using the corresponding ketones and suitably functionalized indoles. The % yield and M+H4 are indicated in parentheses.
2,2,2-TrifluoiO-l-(5-fluoro-lH-indol-3-yl)-l-(l-/7-tolyl-lH-indazol-5-yl)ethanol (48%, M+Η+: 440);
2,2,2-Trifluoro- 1 -(5-fluoro- lH-indol-3-yl)- 1 -[ 1 -(2-fluorophenyl)-lH-indazol-5-yl]ethanol (47%, M+Η+: 444);
2,2,2-Trifluoro- 1 -(5-fluoro- lH-indol-3-yl)- 1 -[I -(4-methoxyphenyl)- lH-indazol-5-yl]ethanol (46%, M+Η+: 456);
2,2,2-TrifluoiO-l-(5-fluoro-lH-indol-3-yl)-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol (35%, M+Η* : 427);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methoxy-4-methyl-lH-indol-3- yl)ethanol (14%, M+Η+: 470);
l-(4-ChloiO-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol (7%, M+Η1": 460);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methoxy-lH-indol-3-yl)ethanol (20%, M+Η+: 456);
1 -(2,5-Dimethyl- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol (20%, M+Η+: 454);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methoxy-lH-indol-3-yl)ethanol (34%, M+Η÷: 456); 2,2,2-TrifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-3-yl)ethanol (36%, M+Η+: 426);
1 -(6-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol (12%; M+Η+: 505);
1 -(7-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol (48%; M+Η+: 505);
1 -(5-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol (39%, MH-H+: 505);
2,2,2-Tπfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methyl-lH-indol-3-yl)ethanol (32%, IVU-H+: 440);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(2-methyl-lH-indol-3-yl)ethanol (34%, M+Η+: 440);
l-(6-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol (21%, M+Η+: 460);
l-(5-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (17%, MH-H+: 460);
l-(4-Bromo-lH-indol-3-yl)-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (4%, MH-H+: 505);
2,2,2-Trifluoro-l-(5-fluoiO-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (24%, MH-H+: 444);
2,2,2-Trifluoro- 1 -(4-fluoro- 1 H-indol-3-yl)- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]ethanol (17%, MH-H+: 444); 2,2,2-Trifluoro- 1 -(6-fluoro- lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol (26%, M+Η+: 444);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methoxy-lH-indol-3-yl)ethanol (29%, M+Η1": 456);
2,2,2-Trifluoro-l-(7-fluoiO-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol (7%, M+Η+: 444);
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(6-methyl- lH-indol-3-yl)ethanol (33%, M+Η"1": 440);
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methyl-lH-indol-3-yl)ethanol (45%, M+Η+: 440); and
3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole-5- carbonitrile (ll%, M+Η+: 451).
Example 26: 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6- pyridin-3-yI-lH-indoI-3-yl)ethanol
Figure imgf000178_0001
To a solution of the bromoindole (0.100 g, 0.193 mmol) in 5 mL of DMF at room temperature in a microwave tube was added 3-pyridineboronic acid (0.049 g, 0.40 mmol), tetrakis(triphenylphosphine)palladium(0) (0.023 g, 0.020 mmol) in aqueous sodium carbonate solution (2 M, 0.064 g, 0.60 mmol). The resulting reaction mixture was degassed with nitrogen for 10 minutes. The reaction was allowed to heat at 12O0C in the Smith Personal Synthesizer for 2.5 hours. The reaction was cooled to room temperature and 3 mL of saturated ammonium chloride solution was added to quench the reaction. 10 mL of ethyl acetate was added and the organic layer was washed with brine, dried over sodium sulfate, and filtered. The solvent was evaporated in vacuo, and the crude material was purified by flash column chromatography to obtain the desired product (60%; M+H+: 517).
The following examples were synthesized following the procedure illustrated for Example 26 using the corresponding boronic acid and suitably functionalized bromoindoles. The % yield and M+H1" are indicated in parentheses.
2,2,2-Trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-4-yl-lH-indol-3- yl)ethanol (60%, M+Η+: 517);
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(6-furan-2-yl- 1 -methyl- 1 H-indol-3- yl)ethanol (22%, M+Η*: 506); and
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrimidin-5-yl-lH- indol-3-yl)ethanol (25%, M+Η1": 518).
Example 27: 2,2,2-Trifluoro-l-[l-(4-fluorophenyI)-lH-indazoI-5-yl]-l-{6-[(2- methoxyethyI)methylamino]-l-methyI-lH-indoI-3-yl}ethanol
To a stirred degassed solution of the bromoindole (0.050 g, 0.096 mmol) in dioxane at room temperature was added the N-(2-methoxyethyl)methylamine (0.023 g, 0.26 mmol), palladium(II) acetate di-teY-butylbiphenylphosphine catalyst (0.005 mg, catalytic amount), and sodium tert-butoxiάβ (0.019 g,0.200 mmol). The resulting reaction solution was allowed to heat at 9O0C for 2 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and filtered through a CELITE® filter aid pad. The solvent was evaporated in vacuo. The crude material was purified by flash column chromatography to obtain the desired product (57%, M+H+: 527).
The following examples were synthesized following the procedure illustrated for Example 27 using the corresponding amines and suitably functionalized bromoindoles. The % yield and M+BT1" are indicated in parentheses.
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -[6-(2-methoxyethylamino)- 1 -methyl- lH-indol-3-yl]ethanol (47%, M+Η+: 513);
1 -{6-[(2-Dimethylaminoethyl)methylamino]-l -methyl- lH-indol-3-yl} -2,2,2-trifluoro- 1 -[I -(4- fluorophenyl)-lH-indazol-5-yl]ethanol (19%, M+Η+: 540);
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-5-morpholin-4-yl- IH- indol-3-yl)ethanol (55%, M+Η+: 525);
l-[6-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol (43%, M+Ef1": 526);
1 -[5-(2-Dimethylaminoethylamino)- 1 -methyl- lH-indol-3-yl]-2,2,2-trifluoro- 1-[1 -(4- fluorophenyl)-lH-indazol-5-yl]ethanol (33%, M+Η+: 526);
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-6-pyrrolidin- 1 -yl- IH- indol-3-yl)ethanol (41 %, M+Η+: 509); and
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-5-pyrrolidin- 1 -yl- IH- indol-3-yl)ethanol (34%, IVU-H+: 509).
Example 28: N-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-ljy-indazol-5-yl]-l- hydroxyethyI}-lJ9r-indoI-7-yl)methanesulfonamide
Figure imgf000181_0001
Step (a): In a 50 mL flask was placed 2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- (l-methyl-7-nitro-lH-indol-3-yl)ethanol (180 mg, 0.37 mmol) in 3 mL of DMF. To this was added a catalytic amount of 10% Pd/C. The atmosphere was evacuated and hydrogen gas added. This was repeated three times and the reaction allowed to stir under hydrogen gas atmosphere at room temperature for 48 hours. The reaction was then filtered under argon and the filtrate extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo. The residue was then dissolved in minimal DMF and purified by ΗPLC (5-95% CΗ3CN/water/0.1% TFA). The desired peaks were combined and the CH3CN was removed. The aqueous was then basified with saturated sodium bicarbonate solution and extracted with EtOAc. The organics were combined, dried, and evaporated in vacuo to provide 96 mg of the desired product l-(7-amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]ethanol as a white solid (57%, M+Η4": 455).
Step (b): In a 7 mL vial was placed l-(7-amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-
(4-fluorophenyl)-lH-indazol-5-yl]ethanol (35 mg, 0.08 mmol, 1 equiv.) in 1 mL of TΗF. To
' this was added triethylamine (20 μL, 0.16 mmol, 2 equiv.) followed by methanesulfonyl chloride (12 μL, 0.16 mmol, 2 equiv.). This was allowed to stir at room temperature for 2 hours. The reaction was then filtered into an ΗPLC vial and purified by ΗPLC (5-95% CΗ3CN/water/0.1% TFA). The desired fractions were combined and the CH3CN was removed. The aqueous was basified with saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo to provide 12 mg of the desired product as a tan foam (29%, M+H1": 533).
Example 29: iV-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lJBr-indazol-5-yl]-l- hydroxyethyl}-lH-indol-7-yl)methanesulfonamide
Figure imgf000182_0001
Step (a): In a 50 mL flask was placed l-methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]-l-hydroxyethyl}-lH-indole-7-carboxylic acid methyl ester (357 mg, 0.72 mmol) in 2 mL of TΗF and 20 mL of IM NaOH. This was allowed to stir at room temperature. After 2 hours, another 10 mL of TΗF was added and the reaction heated at 5O0C for 18 hours. At this point, 3 pellets of solid NaOH were added and the heating continued. After another 2 hours, another 3 pellets of NaOH were added and the reaction allowed stirring at 5O0C for 72 hours. The reaction was cooled and transferred to a separatory funnel where it was acidifed to pΗ 7 with saturated aqueous ammonium chloride solution. This was extracted with EtOAc and the combined organics were dried, filtered, and evaporated in vacuo to provide 280 mg of the desired product as a tan solid (81%, MH-H+: 484).
Step (b): In a 7 mL vial was placed l-methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]-l-hydroxyethyl}-lH-indole-7-carboxylic acid, (50 mg, 0.1 mmol, 1 equiv.) in 1 mL of DMF. To this was added triethylamine (79 μL, 0.6 mol, 6 equiv.) followed by PyBOP (80 mg, 0.15 mmol, 1.5 equiv.). After 5 minutes, ammonium chloride (55 mg, 1 mmol, 10 equiv.) was added, the reaction was capped, and the reaction allowed to stir at room temperature for 18 hours. The mixture was filtered into a vial and purified by ΗPLC (5-90% CΗsCN/water/0.1% TFA). The desired fractions were combined and the CH3CN was removed. The aqueous portion was basified with saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo to provide 36 mg of the desired product as a white solid (72%, M+H+: 483).
The following examples were synthesized following the procedure illustrated for Example 29, step (b) using the corresponding amines and suitably functionalized indole-carboxylic acids. The % yield and M+H* are indicated in parentheses. l-Methyl-3-{2,2,2-trifluoiO-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydiOxyethyl}-lH- indole-7-carboxylic acid methylamide (70% M+Η"1"; 497);
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-cyanoethyl)amide (63%, M+Η1": 536);
1 -Methyl-3- {2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -hydroxy ethyl} - IH- indole-7-carboxylic acid (2-methoxyethyl)amide (79%, M+Η+: 541);
1 -Methyl-3- {2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -hydroxyethyl}- IH- indole-7-carboxylic acid (2-methoxyethyl)methylamide (77%< M+Η4": 555);
1 -Methyl-3- {2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid carbamoylmethylamide (74%, M+Η4": 540);
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid cyanomethylamide (80%, M+Η4": 522); and
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole- 7-carboxylic acid amide (66%, M+Η+: 509).
Example 30: 2,2,2-Trifluoro-l-phenyl-l-(l-phenyI-liar-indol-5-yI)ethanol
Figure imgf000183_0001
Step (a): To a solution of 1 -phenyl- lH-indole-5-carbonitrile (2.51 g, 11.47 mmol) in 60 niL of CH2Cl2 at O0C was added DIBAL-H (IM in THF, 16 niL, 16 mmol). The resulting yellow suspension was stirred for 2 hours and then poured into 30 mL of cold IN HCl solution. The biphasic system was cooled to O0C and then basified to pH 8 by the addition of saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with three 20 mL portions of CH2Cl2. The combined organic phase was dried over sodium sulfate, filtered, and then concentrated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-80% hexanes/EtOAc). The desired product 1-phenyl-lH- indole-5-carbaldehyde was obtained as a light yellow solid (1.77 g, 70% yield; MH-H+: 222).
Step (b): To a solution of l-phenyl-lH-indole-5-carbaldehyde (1.2 g, 5.4 mmol) in 10 mL of TΗF at O0C was added a solution Of TMSCF3 in TΗF (0.9 g, 6.4 mmol). The resulting light yellow solution was stirred at O0C for 15 minutes, then tetrabutylammonium fluoride (TBAF) (IM in TΗF, 1.6 mL, 1.6 mmol) was added. The reaction mixture was allowed to warm up to room temperature and then stirred for an additional 14 hours. The TΗF was evaporated in vacuo and the resulting residue was dissolved in 20 mL of EtOAc, washed with three 25 mL portions of water, and a 25 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 80% hexanes/EtOAc). The desired product 2,2,2- trifluoro-l-(l-phenyl-lH-indol-5-yl)ethanol was obtained as a light yellow solid (1.4 g, 87.0% yield; M+Η+: 292).
Step (c): A suspension of Dess-Martin periodinane (2.4 g, 5.6 mmol) and 2,2,2-trifluoro-l-(l- phenyl-lH-indol-5-yl)ethanol (1.4 g, 4.8 mmol) in 20 mL of CH2Cl2 was allowed to stir for 12 hours at room temperature. The reaction mixture was added to 150 mL of hexane and the resulting white precipitate was filtered through a pad of CEL1TE® filter aid. The combined organic solution was washed with three 25 mL portions of sodium bicarbonate and a 25 mL portion of brine, dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 85% hexanes/EtOAc) The desired product 2,2,2-trifluoro-l-(l-ρhenyl-lH-indol-5-yl)ethanone was obtained as a white solid (1.3 g, 91.0% yield; M+rf": 290).
Step (d): To a solution of 2,2,2-trifluoiO-l-(l-phenyl-lH-indol-5-yl)ethanone (50.0 mg, 0.2 mmol) in 0.5 mL of TΗF was added phenylmagnesium bromide (1.0 M, 1.0 mL, 1.0 mmol) at room temperature. The solution was stirred at this temperature for 12.0 hours. The reaction was quenched with 2 mL of saturated aqueous ammonium chloride solution and 3.0 mL of water. The aqueous layer was extracted with three 5 mL portions of EtOAc and the combined organic layers were dried over sodium sulfate, filtered, and the solvent was evaporated in vacuo. The crude material was purified by flash column chromatography with silica gel (eluted with 100%-85% hexanes/EtOAc). The desired product 2,2,2-Trifluoro-l-phenyl-l-(l-phenyl- lH-indol-5-yl)ethanol was obtained as a white solid (49.0 mg, 80% yield; IVU-H+: 368).
The following examples were synthesized following the procedure illustrated for Example 30, step (d), using the corresponding Grignard or equivalent organometallic reagent. The percent yield of the reaction and the M+Η+ are indicated in parentheses.
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)-l -(I -phenyl- lH-indol-5-yl)ethanol (66%, M+Η+: 436); and
2,2,2-Trifluoro-l-naphthalen-l-yl-l-(l-phenyl-lH-indol-5-yl)ethanol (78%, M+Η+: 418).
Example 31: N-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5- yl)ethyl]phenyl}acetamide
Figure imgf000185_0001
Step (a): In a 100 mL flask was placed l-[3-(2,5-dimethylpyrrol-l-yl)phenyl]-2,2,2-trifluoro-l- (l-phenyl-lH-indazol-5-yl)ethanol (112 mg, 0.24 mmol, 1 equiv.) in 7 mL of EtOH and 3 mL of water. To this was added hydroxylamine hydrochloride (168 mg, 2.4 mmol, 10 equiv.) and the reaction refluxed for 18 hours. The EtOH was then removed and the reaction diluted with EtOAc. This was then basified with saturated aqueous sodium bicarbonate solution, transferred to a separatory funnel, and extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography to provide 25 mg of l-(3-aminophenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol as a pale orange solid (70%, MH-H+: 462). Step (b): In a 10 mL flask was placed l-(3-aminophenyl)-2,2,2-trifluoiO-l-(l-phenyl-lH- indazol-5-yl)ethanol (20 mg, 0.05 mmol, 1 equiv.) in 1 mL of pyridine. To this was added 1 drop of acetyl chloride. After 2 hours, the pyridine was removed and the residue was purified by flash chromatography to provide 16.4 mg of the desired product as a white solid (74%, M+Η+: 426).
Example 32: l-(l-Allyl-lH-indol-3-yI)-l-[l-(4-fluorophenyl)-lH-indazol-5-yI]-2- methylpropan-1-ol
Figure imgf000186_0001
Step (a): In a 250 mL flask was placed 5-bromo-l-(4-fluorophenyl)-lH-indazole (3.5 g 11.5 mmol, 1.1 equiv.) in 50 mL of dry TΗF. This was cooled to -780C. In a separate vial was placed l-allyl-lH-indole-3-carbaldehyde (2.0 g 10.8 mmol, 1 equiv.) in 5 mL of TΗF and this was cooled to -780C. n-BuLi (2.5 M in hexanes, 4.7 mL, 11.5 mmol, 1.1 equiv) was added to the 5-bromo-l-(4-fluorophenyl)-lH-indazole by syringe quickly at which point, the solution of l-allyl-lH-indole-3-carbaldehyde was added in one portion. The reaction was allowed to stir at -780C for 30 minutes at which point it was quenched with water and allowed to come to room temperature. The reaction was then diluted with brine and extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography (0-30% EtOAc/hexanes) to provide 1.5 g of (l-allyl-lH-indol-3-yl)-[l- (4-fluorophenyl)-lH-indazol-5-yl]methanol as a tan solid (35%, MMH+: 398). Step (b): In a 100 mL flask was placed (l-allyl-lH-indol-3-yl)-[l-(4-fluoiOphenyl)-lH-indazol- 5-yl]methanol (1.3 g, 3.2 mmol, 1 equiv.) in 50 mL Of CH2Cl2. This was cooled to O0C where pyridinium chlorochromate (PCC; 764 mg, 3.5 mmol, 1.1 equiv.) was added. After 5 minutes, the ice bath was removed and the reaction allowed to stir at room temperature for 18 hours. The reaction was transferred to a separatory funnel and diluted with CH2Cl2 and washed with saturated aqueous sodium bicarbonate solution. The organic was removed, dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography (0-30% EtOAc- hexanes) to provide 820 mg of (l-allyl-lH-indol-3-yl)-[l-(4-fluorophenyl)-lH-indazol-5- yljmethanone as a tan solid which was used without further purification (65%, M+Η+: 396).
Step (c): In a 25 mL flask was placed (l-allyl-lH-indol-3-yl)-[l-(4-fluorophenyl)-lH-indazol- 5-yl]methanone (100 mg, 0.3 mmol, 1 equiv.) in 5 mL of TΗF. This was cooled to -780C where isopropyl lithium (0.7 M in pentane, 0.43 mL, 1.2 equiv.) was added dropwise. The reaction was then allowed to stir for 30 minutes. The reaction was then diluted with water and allowed to come to room temperature. The mixture was transferred to a separatory funnel and extracted with EtOAc. The combined organics were dried, filtered, and evaporated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc/hexanes) to provide 21 mg of the desired compound as a white solid (19%, M+Η4": 440).
The following examples were synthesized following the procedure illustrated for Example 32, step (c), reacting the corresponding Grignard or equivalent organometallic reagent with the desired biarylketones. The percent yield of the reaction and the IVU-H+ are indicated in parentheses.
l-(l-Phenyl-lH-indazol-5-yl)-l-quinolin-4-ylethanol (65%, M+Η+: 366);
l-(l-Phenyl-lH-indazol-5-yl)-l-quinolin-4-ylpropan-l-ol (30%, M+Η+: 380);
l-(4-Fluoronaphthalen-l-yl)-l-(l-phenyl-lH-indazol-5-yl)propan-l-ol (81%, M+Η*: 397); and
l-(l-Allyl-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-l-ol (18%, M+Η1": 426). Example 33 : 2,2,2-Trifluoro-l-(4-fluoro-3-hydroxymethyIphenyl)-l-(l-phenyI-lH- indazol-5-yl)ethanoI
Figure imgf000188_0001
Figure imgf000188_0002
Step (a): To a solution of 2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanone (0.150 g, 0.517 mmol) in TΗF at room temperature was added the 3-(l,3-dioxan-2-yl)4-fluorophenyl magnesium bromide (0.25 M in TΗF, 6.0 mL, 1.5 mmol). The resulting solution was allowed to stir overnight at room temperature. The reaction was quenched with a saturated solution of ammonium chloride. Ethyl acetate was added and the organic layer was washed with brine, dried over sodium sulfate, and filtered. The solvent was evaporated in vacuo, and the crude material was purified by flash column chromatography to obtain the desired product 1 -(3-1,3- dioxinan-2-yl-4-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol (82%,
M+Η+: 473).
Step (b): To a solution of l-(3-l,3-dioxinan-2-yl-4-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl- lH-indazol-5-yl)ethanol (0.2 g, 0.423 mmol) in TΗF at room temperature was added a solution of HCl (2 M, 5 mL). The resulting solution was allowed to stir overnight at room temperature. The reaction mixture was neutralized by saturated aqueous sodium carbonate solution to pΗ 7. Ethyl acetate was added and the organic layers were washed with brine, dried over sodium sulfate and filtered .The solvent was evaporated in vacuo, and the crude material was purified by flash column chromatography to obtain the desired product 2-fluoro-5-[2,2,2-trifluoro-l- hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]benzaldehyde (48%, M+Η+: 415).
Step (c): To a stirred solution of 2-fluoiO-5-[2,2,2-trifluoiO-l-hydroxy-l-(l-phenyl-lH-indazol- 5-yl)ethyl]benzaldehyde (0.04 g, 0.097 mmol) in dichloromethane at room temperature was added sodium triacetoxyborohydride (0.032 g, 0.15 mmol). The reaction mixture was allowed to be stirred at room temperature overnight, then diluted with 3 mL of dichloromethane and 4 mL of saturated aqueous sodium bicarbonate solution. 10 mL of ethyl acetate was added and the organic layer was washed with brine, dried over sodium sulfate, and filtered. The solvents were evaporated in vacuo, and the crude material was purified by flash column chromatography to obtain the desired product 2,2,2-trifluoro-l-(4-fluoro-3-hydroxymethylphenyl)-l-(l-phenyl- lH-indazol-5-yl)ethanol (80%, IVM-H+: 417).
Example 34: 3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenoI
Figure imgf000189_0001
To a solution of 2,2,2-trifluoro-l-(3-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol (0.054 g, 0.136 mmol) in CH2Cl2 at O0C was added the BBr3 (IM in CH2Cl2, 1.36 mL, 1.36 mmol) dropwise. The resulting solution was stirred for 2 days at 50C. The reaction was allowed to warmed up to room temperature, then quenched with 2 mL of MeOH. Ethyl acetate was added to the reaction and the organic layer was washed with brine, dried over sodium sulfate, and filtered. The solvent was evaporated in vacuo, and the crude material was purified by flash column chromatography to obtain the desired compound 3-[2,2,2-trifluoro-l-hydroxy- l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol (38%, M+Η+: 389).
Assessment of Biological Properties Compounds of the invention were evaluated for binding to the steroid receptor by a fluorescence polarization competitive binding assay. Detailed descriptions for preparation of recombinant glucocorticoid receptor (GR) complex used in the assay is described in U.S. Patent Application Publication No. US 2003/0017503, filed May 20, 2002, and incorporated herein by reference in its entirety. Preparation of the tetramethylrhodamine (TAMRA)-labeled dexamethasone probe was accomplished using a standard literature procedure (M. Pons ei al, J. Steroid Biochem., 1985, 22, pp. 267-273).
A. Glucocorticoid Receptor Competitive Binding Assay Step 1. Characterization of the Fluorescent Probe
The wavelengths for maximum excitation and emission of the fluorescent probe should first be measured. An example of such a probe is rhodamine (TAMRA)-labeled dexamethasone.
The affinity of the probe for the steroid receptor was then determined in a titration experiment. The fluorescence polarization value of the probe in assay buffer was measured on an SLM- 8100 fluorometer using the excitation and emission maximum values described above. Aliquots of expression vector lysate were added and fluorescence polarization was measured after each addition until no further change in polarization value was observed. Non-linear least squares regression analysis was used to calculate the dissociation constant of the probe from the polarization values obtained for lysate binding to the probe.
Step 2. Screening for Inhibitors of Probe Binding
This assay uses fluorescence polarization (FP) to quantitate the ability of test compounds to compete with tetramethylrhodamine (TAMRA)-labeled dexamethasone for binding to a human glucocorticoid receptor (GR) complex prepared from an insect expression system. The assay buffer was: 10 mM TES, 50 mM KCl, 20 mM Na2MoO4»2H2O, 1.5 mM EDTA, 0.04% w/v CHAPS, 10% v/v glycerol, 1 mM dithiothreitol, pH 7.4. Test compounds were dissolved to 1 mM in neat DMSO and then further diluted to 10x assay concentration in assay buffer supplemented with 10% v/v DMSO. Test compounds were serially diluted at 10x assay concentrations in 10% DMSO-containing buffer in 96-well polypropylene plates. Binding reaction mixtures were prepared in 96-well black Dynex microtiter plates by sequential addition of the following assay components to each well: 15 μL of 10x test compound solution, 85 μL of GR-containing baculovirus lysate diluted 1:170 in assay buffer, and 50 μL of 15 iiM TAMRA- labeled dexamethasone. Positive controls were reaction mixtures containing no test compound; negative controls (blanks) were reaction mixtures containing 0.7 μM to 2 μM dexamethasone. The binding reactions were incubated for 1 hour at room temperature and then read for fluorescence polarization in the LJL Analyst set to 550 nm excitation and 580 nra emission, with the Rhodamine 561 dichroic mirror installed. IC50 values were determined by iterative non-linear curve fitting of the FP signal data to a 4-parameter logistic equation.
Compounds found to bind to the glucocorticoid receptor may be evaluated for binding to the progesterone receptor (PR), estrogen receptor (ER), and mineralocorticoid receptors to evaluate the compound's selectivity for GR. The protocols for PR and MR are identical to the above GR method, with the following exceptions: PR insect cell lysate is diluted 1:7.1 and MR lysate diluted 1 :9.4. PR probe is TAMRA-labeled mifepristone, used at a final concentration of 5 nM in the assay, and the negative controls (blanks) were reactions containing mifepristone at 0.7 μM to 2 μM.
The ER protocol is similar to the above protocols, but uses PanVera kit receptor, fluorescein- labeled probe. The assay components are made in the same volumes as above, to produce final assay concentrations for ER of 15 nM and ES2 probe of 1 nM. In addition, the component order of addition is modified from the above assays: probe is added to the plate first, followed by receptor and test compound. The plates are read in the LJL Analyst set to 485 nm excitation and 530 nm emission, with the Fluorescein 505 dichroic mirror installed.
Compounds found to bind to the glucocorticoid receptor may be evaluated for dissociation of transactivation and transrepression by assays cited in the Background of the Invention (CM. Bamberger and H.M. Schulte, Eur. J. Clin. Invest., 2000, 30 (suppl. 3) 6-9) or by the assays described below.
B. Glucocorticoid Receptor Cell Assays 1. Induction ofAromatase in Fibroblasts (Cell Assay for Transactivation)
Dexamethasone, a synthetic ligand to the glucocorticoid receptor (GR), induces expression of aromatase in human foreskin fibroblast cells. The activity of aromatase is measured by the conversion of testosterone to estradiol in culture media. Compounds that exhibit binding to GR are evaluated for their ability to induce aromatase activity in human foreskin fibroblasts.
Human foreskin fibroblast cells (ATCC Cat. No. CRL-2429, designation CCDl 12SK) are plated on 96 well plates at 50,000 cells per well 5 days before use, in Iscove's Modified Dulbecco's Media (GibcoBRL Life Technologies Cat No. 12440-053) supplemented with 10% charcoal filtered FBS (Clonetech Cat No. SH30068) and Gentamycin (GibcoBRL Life Technologies Cat. No. 15710-064). On the day of the experiment, the media in the wells is replaced with fresh media. Cells are treated with test compounds to final concentrations of 10"5 M to 10"8 M, and testosterone to a final concentration of 300 ng/mL. Each well has a total volume of 100 μL. Samples are made in duplicates. Control wells include: (a) wells that receive testosterone only, and (b) wells that receive testosterone plus 2 μM of dexamethasone to provide maximum induction of aromatase. Plates are incubated at 370C overnight (15 to 18 hours), and supernatants are harvested at the end of incubation. Estradiol in the supernatant is measured using ELISA kits for estradiol (made by ALPCO, obtained from American Laboratory Products Cat. No. 020-DR-2693) according to the manufacture's instruction. The amount of estradiol is inversely proportional to the ELISA signals in each well. The extent of aromatase induction by test compounds is expressed as a relative percentage to dexamethasone. EC50 values of test compounds are derived by non-linear curve fitting.
2. Inhibition of IL-6 Production in Fibroblasts (Cell Assay for Transrepression) Human foreskin fibroblast cells produce IL-6 in response to stimulation by proinflammatory cytokine IL-I. This inflammatory response, as measured by the production of IL-6, can be effectively inhibited by dexamethasone, a synthetic ligand to the glucocorticoid receptor (GR). Compounds that exhibit binding to GR are evaluated for their ability to inhibit IL-6 production in human foreskin fibroblasts.
Human foreskin fibroblast cells (ATCC Cat. No. CRL-2429) are plated on 96 well plates at 5,000 cells per well the day before use, in Iscove's Modified Dulbecco's Media (GibcoBRL Life Technologies Cat. No. 12440-053) supplemented with 10% charcoal filtered FBS (Clonetech Cat. No. SH30068) and Gentamycin (GibcoBRL Life Technologies Cat. No. 15710- 064). On the next day, media in the wells is replaced with fresh media. Cells are treated with IL-I (rhIL-lα, R&D Systems Cat. No. 200-LA) to a final concentration of 1 ng/mL, and with test compounds to final concentrations of 10"5 M to 10"8 M, in a total volume of 200 μL per well. Samples are done in duplicates. Background control wells do not receive test compounds or IL-I. Positive control wells receive IL-I only and represent maximum (or 100%) amount of IL-6 production. Plates are incubated at 37°C overnight (15 to 18 hours), and supematants are harvested at the end of incubation. IL-6 levels in the supematants are determined by the ELISA kits for IL-6 (MedSystems Diagnostics GmbH, Vienna, Austria, Cat. No. BMS213TEN) according to manufacture's instructions. The extent of inhibition of IL-6 by test compounds is expressed in percentage relative to positive controls. IC50 values of test compounds are derived by non-linear curve fitting.
Evaluation of agonist or antagonist activity of compounds binding to the glucocorticoid receptor may be determined by any of the assays.
3. Modulation of Tyrosine Aminotransferase (TAT) Induction in Rat Hepatoma Cells
Testing of compounds for agonist or antagonist activity in induction of tyrosine aminotransferase (TAT) in rat hepatoma cells.
H4-II-E-C3 cells were incubated overnight in 96 well plates (20,000 cells/100 μL/well) in MEM medium containing 10% heat inactivated FBS and 1% nonessential amino acids. On the next day, cells were stimulated with the indicated concentrations of dexamethasone or test compound (dissolved in DMSO, final DMSO concentration 0.2%) for 18 hours. Control cells were treated with 0.2% DMSO. After 18 hours, the cells were lysed in a buffer containing
0.1% Triton X-IOO and the TAT activity was measured in a photometric assay using tyrosine and alpha-ketoglutarate as substrates.
For measuring antagonist activity, the hepatoma cells were pre-stimulated by addition of dexamethasone (concentration ranges from 3 x 10"9 M to 3 x 10"8 M) shortly before the test compound was applied to the cells. The steroidal non-selective GR/PR antagonist mifepristone was used as control.
4. Modulation ofMMTV-Luc Induction in HeLa Cells Testing of compounds for agonist or antagonist activity in stimulation of MMTV-(mouse mammary tumor virus) promoter in HeLa cells.
HeLa cells were stably co-transfected with the pHHLuc-plasmid containing a fragment of the MMTV-LTR (-200 to +100 relative to the transcription start site) cloned in front of the luciferase gene (Norden, 1988) and the pcDNA3.1 plasmid (Invitrogen) constitutively expressing the resistance for the selective antibiotic GENETICIN®. Clones with best induction of the MMTV-promoter were selected and used for further experiments.
Cells were cultured overnight in DMEM medium without phenol red, supplemented with 3% CCS (charcoal treated calf serum) and then transferred to 96 well plates (15,000 cells/100 μL/well). On the next day, activation of the MMTV-promoter was stimulated by addition of test compound or dexamethasone dissolved in DMSO (final concentration 0.2%). Control cells were treated with DMSO only. After 18 hours, the cells were lysed with cell lysis reagent (Promega, Cat. No. E1531), luciferase assay reagent (Promega, Cat. No. E1501) was added and the glow luminescence was measured using a luminometer (BMG, Offenburg).
For measuring antagonist activity, the MMTV-promoter was pre-stimulated by adding dexamethasone (3 x 10"9 M to 3 x 10"8 M) shortly before the test compound was applied to the cells. The steroidal non-selective GR/PR antagonist mifepristone was used as control.
5. Modulation ofIL-8 Production in U937 Cells
Testing of compounds for agonist or antagonist activity in GR-mediated inhibition of LPS- induced IL-8 secretion in U-937 cells.
U-937 cells were incubated for 2 to 4 days in RPMI 1640 medium containing 10% CCS (charcoal treated calf serum). The cells were transferred to 96 well plates (40,000 cells/100 μL/well) and stimulated with 1 μg/mL LPS (dissolved in PBS) in the presence or absence of dexamethasone or test compound (dissolved in DMSO, final concentration 0.2%). Control cells were treated with 0.2% DMSO. After 18 hours, the IL-8 concentration in the cell supernatant was measured by ELISA, using the "OptEIA human IL-8 set" (Pharmingen, Cat. No. 2654KI). For measuring antagonist activity, the LPS-induced IL-8 secretion was inhibited by adding dexamethasone (3 x 10"9 M to 3 x 10"8 M) shortly before the test compound was applied to the cells. The steroidal non-selective GR/PR antagonist mifepristone was used as control.
6. Modulation oflCAM-Luc Expression in HeLa Cells
Testing of compounds for agonist or antagonist activity in inhibition of TNF-alpha-induced activation of the ICAM-promoter in HeLa cells.
HeLa cells were stably co-transfected with a plasmid containing a 1.3 kb fragment of the human ICAM-promoter (-1353 to -9 relative to the transcription start site, Ledebur and Parks, 1995) cloned in front of the luciferase gene and the pcDNA3.1 plasmid (Invitrogen) which constitutively expresses the resistance for the antibiotic GENETICIN®. Clones with best induction of the ICAM-promoter were selected and used for further experiments. Cells were transferred to 96 well plates (15,000 cells/100 μL/well) in DMEM medium supplemented with 3% CCS. On the following day the activation of the ICAM-promoter was induced by addition of 10 ng/mL recombinant TNF-alpha (R&D System, Cat. No. 210-TA). Simultaneously the cells were treated with the test compound or dexamethasone (dissolved in DMSO, final concentration 0.2%). Control cells were treated with DMSO only. After 18 hours, the cells were lysed with cell lysis reagent (Promega, Cat. No. El 531), luciferase assay reagent (Promega, Cat. No. E 1501) was added and glow luminescence was measured using a luminometer (BMG, Offenburg).
For measuring antagonist activity, the TNF-alpha-induced activation of the ICAM-promoter was inhibited by adding dexamethasone (3 x lO'9 M to 3 x 10"8 M) shortly before the test compound was applied to the cells. The steroidal non-selective GR/PR antagonist mifepristone was used as control.
In general, the preferred potency range in the above assays is between 0.1 nM and 10 μM, the more preferred potency range is 0.1 nM to 1 μM, and the most preferred potency range is 0.1 nM to 10O nM. Representative compounds of the invention have been tested and have shown activity as modulators of the glucocorticoid receptor function in one or more of the above assays. For example, the following representative compounds of the invention have demonstrated potent activity (between 0.1 nM and 100 nM) in the GR binding assay:
l-Biphenyl-3-yl-2,2,2-tπfluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3,4-Difluorophenyl)-2,2,2-trifluoiO- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(3,5-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-ChloiO-5-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-ChloiO-3-metliylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3 -Chloro-4-fluorophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
1 -(4-Chloro-3-fluorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifiuoro- 1 -naphthalen- 1 -yl- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methylnaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluorophenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol; 2,2,2-Tϊifluoro- 1 -(3-fluoro-4-methylphenyl)- 1 -(I -phenyl- IH- indazol-5-yl)ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-fluoro-4-methylphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-tπfluoiO-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
1 -(4-Dimethylaminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -(I -phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxynaphthalen- 1 -yl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 -(lH-indol-4-yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
1,1,1 -Trifluoro-3-(3 -fluorophenyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-phenyl-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(3 ,5-Difluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-Benzo[ό]thiophen-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
l-Benzo[δ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 - [ 1 -(4-fluorophenyl)- lH-indazol-5 -yl]- 1 -phenylethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -naphthalen-1 -ylethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(4-methylnaphthalen-l-yl)ethanol;
l-Benzo[&]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoiO-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol; and
1 -(2,2-Difluoro-l ,3-benzodioxol-4-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol.
The following compounds of the invention have demonstrated agonistic activity by inhibiting IL-6 production in Fibroblasts (Cell Assay for Transrepression):
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(4-methylnaphthalen- 1 -yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol; l-Benzo[ό]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -Benzo[έ]thiophen-3-yl-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1-yl)- 1 -(I -phenyl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -phenyl- 1 H-indazol-5-yl)ethanol; and
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol.
Methods of Therapeutic Use As pointed out above, the compounds of the invention are useful in modulating the glucocorticoid receptor function. In doing so, these compounds have therapeutic use in treating disease-states and conditions mediated by the glucocorticoid receptor function or that would benefit from modulation of the glucocorticoid receptor function.
As the compounds of the invention modulate the glucocorticoid receptor function, they have very useful anti-inflammatory and antiallergic, immune-suppressive, and anti-proliferative activity and they can be used in patients as drugs, particularly in the form of pharmaceutical compositions as set forth below, for the treatment of disease-states and conditions.
The agonist compounds according to the invention can be used in patients as drugs for the treatment of the following disease-states or indications that are accompanied by inflammatory, allergic, and/or proliferative processes:
(i) Lung diseases: chronic, obstructive lung diseases of any genesis, particularly bronchial asthma and chronic obstructive pulmonary disease (COPD); adult respiratory distress syndrome (ARDS); bronchiectasis; bronchitis of various genesis; all forms of restrictive lung diseases, particularly allergic alveolitis; all forms of lung edema, particularly toxic lung edema; all forms of interstitial lung diseases of any genesis, e.g., radiation pneumonitis; and sarcoidosis and granulomatoses, particularly Boeck disease; (ii) Rheumatic diseases or autoimmune diseases or joint diseases: all forms of rheumatic diseases, especially rheumatoid arthritis, acute rheumatic fever, and polymyalgia rheumatica; reactive arthritis; rheumatic soft tissue diseases; inflammatory soft tissue diseases of other genesis; arthritic symptoms in degenerative joint diseases (arthroses); traumatic arthritis; collagenoses of any genesis, e.g., systemic lupus erythematosus, scleroderma, polymyositis, dermatomyositis, Sjogren syndrome, Still disease, and Felty syndrome; (iii) Allergic diseases: all forms of allergic reactions, e.g., angioneurotic edema, hay fever, insect bites, allergic reactions to drugs, blood derivatives, contrast agents, etc., anaphylactic shock (anaphylaxis), urticaria, angioneurotic edema, and contact dermatitis;
(iv) Vasculitis diseases: panarteritis nodosa, polyarteritis nodosa, arteritis temporalis, Wegner granulomatosis, giant cell arthritis, and erythema nodosum;
(v) Dermatological diseases: atopic dermatitis, particularly in children; psoriasis; pityriasis rubra pilaris; erythematous diseases triggered by various noxa, e.g., rays, chemicals, burns, etc.; bullous dermatoses; diseases of the lichenoid complex; pruritus (e.g., of allergic genesis); seborrheic dermatitis; rosacea; pemphigus vulgaris; erythema multiforme exudativum; balanitis; vulvitis; hair loss, such as occurs in alopecia areata; and cutaneous T cell lymphomas;
(vi) Renal diseases: nephrotic syndrome; and all types of nephritis, e.g., glomerulonephritis; (vii) Hepatic diseases: acute liver cell disintegration; acute hepatitis of various genesis, e.g., viral, toxic, drug-induced; and chronically aggressive and/or chronically intermittent hepatitis;
(viii) Gastrointestinal diseases: inflammatory bowel diseases, e.g., regional enteritis (Crohn disease), colitis ulcerosa; gastritis; peptic esophagitis (refluxoesophagitis); and gastroenteritis of other genesis, e.g., nontropical sprue;
(ix) Proctological diseases: anal eczema; fissures; hemorrhoids; and idiopathic proctitis; (x) Eye diseases: allergic keratitis, uveitis, or iritis; conjunctivitis; blepharitis; neuritis nervi optici; choroiditis; and sympathetic ophthalmia; (xi) Diseases of the ear, nose, and throat (ENT) area: allergic rhinitis or hay fever; otitis externa, e.g., caused by contact eczema, infection, etc.; and otitis media;
(xii) Neurological diseases: brain edema, particularly tumor-related brain edema; multiple sclerosis; acute encephalomyelitis; meningitis; acute spinal cord injury; stroke; and various forms of seizures, e.g., nodding spasms;
(xiii) Blood diseases: acquired hemolytic anemia; and idiopathic thrombocytopenia;
(xiv) Tumor diseases: acute lymphatic leukemia; malignant lymphoma; lymphogranulomatoses; lymphosarcoma; extensive metastases, particularly in mammary, bronchial, and prostatic carcinoma; (xv) Endocrine diseases: endocrine ophthalmopathy; endocrine orbitopathia; thyrotoxic crisis; Thyroiditis de Quervain; Hashimoto thyroiditis; Morbus Basedow; granulomatous thyroiditis; struma lymphomatosa; and Grave disease;
(xvi) Organ and tissue transplantations and graft-versus-host diseases;
(xvii) Severe states of shock, e.g., septic shock, anaphylactic shock, and systemic inflammatory response syndrome (SIRS);
(xviii) Substitution therapy in: congenital primary adrenal insufficiency, e.g., adrenogenital syndrome; acquired primary adrenal insufficiency, e.g., Addison disease, autoimmune adrenalitis, post-infection, tumors, metastases, etc.; congenital secondary adrenal insufficiency, e.g., congenital hypopituitarism; and acquired secondary adrenal insufficiency, e.g., post-infection, tumors, metastases, etc.;
(xix) Pain of inflammatory genesis, e.g., lumbago; and
(xx) various other disease-states or conditions including type I diabetes (insulin-dependent diabetes), osteoarthritis, Guillain-Barre syndrome, restenosis following percutaneous transluminal coronary angioplasty, Alzheimer disease, acute and chronic pain, atherosclerosis, reperfusion injury, bone resorption diseases, congestive heart failure, myocardial infarction, thermal injury, multiple organ injury secondary to trauma, acute purulent meningitis, necrotizing enterocolitis and syndromes associated with hemodialysis, leukopheresis, and granulocyte transfusion.
In addition, the compounds according to the invention can be used for the treatment of any other disease-states or conditions not mentioned above which have been treated, are treated, or will be treated with synthetic glucocorticoids (see, e.g., HJ. Hatz, Glucocorticoide: Imniunologische Grundlagen, Pharmakologie und Therapierichtlinien [Glucocorticoids: Immunological Fundamentals, Pharmacology, and Therapeutic Guidelines], Stuttgart: Verlagsgesellschaft mbH, 1998, which is hereby incorporated by reference in its entirety). Most or all of the indications (i) through (xx) mentioned above are described in detail in HJ. Hatz, Glucocorticoide: Immunologische Grundlagen, Pharmakologie und Therapierichtlinien. Furthermore, the compounds of the invention can also be used to treat disorders other than those listed above or mentioned or discussed herein, including in the Background of the Invention.
The antagonist compounds according to the invention, whether full antagonists or partial antagonists, can be used in patients as drugs for the treatment of the following disease-states or indications, without limitation: type II diabetes (non-insulin-dependent diabetes); obesity; cardiovascular diseases; hypertension; arteriosclerosis; neurological diseases, such as psychosis and depression; adrenal and pituitary tumors; glaucoma; and Gushing syndrome based on an ACTH-secreting tumor like pituitary adenoma. In particular, the compounds of the invention are useful for treating obesity and all disease-states and indications related to a deregulated fatty acids metabolism such as hypertension, atherosclerosis, and other cardiovascular diseases. Using the compounds of the invention that are GR antagonists, it should be possible to antagonize both the carbohydrate metabolism and fatty acids metabolism. Thus, the antagonist compounds of the invention are useful in treating all disease-states and conditions that involve increased carbohydrate, protein, and lipid metabolism and would include disease-states and conditions leading to catabolism like muscle frailty (as an example of protein metabolism).
Methods of Diagnostic Use The compounds of the invention may also be used in diagnostic applications and for commercial and other purposes as standards in competitive binding assays. In such uses, the compounds of the invention may be used in the form of the compounds themselves or they may be modified by attaching a radioisotope, luminescence, fluorescent label or the like in order to obtain a radioisotope, luminescence, or fluorescent probe, as would be known by one of skill in the art and as outlined in Handbook of Fluorescent Probes and Research Chemicals, 6th Edition, R.P. Haugland (ed.), Eugene: Molecular Probes, 1996; Fluorescence and Luminescence Probes for Biological Activity. W.T. Mason (ed.), San Diego: Academic Press, 1993; Receptor-Li gand Interaction. A Practical Approach. E.C. Hulme (ed.), Oxford: IRJL Press, 1992, each of which is hereby incorporated by reference in their entireties.
General Administration and Pharmaceutical Compositions When used as pharmaceuticals, the compounds of the invention are typically administered in the form of a pharmaceutical composition. Such compositions can be prepared using procedures well known in the pharmaceutical art and comprise at least one compound of the invention. The compounds of the invention may also be administered alone or in combination with adjuvants that enhance stability of the compounds of the invention, facilitate administration of pharmaceutical compositions containing them in certain embodiments, provide increased dissolution or dispersion, increased inhibitory activity, provide adjunct therapy, and the like. The compounds according to the invention may be used on their own or in conjunction with other active substances according to the invention, optionally also in conjunction with other pharmacologically active substances. In general, the compounds of this invention are administered in a therapeutically or pharmaceutically effective amount, but may be administered in lower amounts for diagnostic or other purposes.
In particular, the compounds of the invention are useful in combination with glucocorticoids or corticosteroids. As pointed out above, standard therapy for a variety of immune and inflammatory disorders includes administration of corticosteroids, which have the ability to suppress immunologic and inflammatory responses. (A.P. Truhan et al, Annals of Allergy, 1989, 62, pp. 375-391; J.D. Baxter, Hospital Practice, 1992, 27, pp. 111-134; R.P. Kimberly, Curr. Opin. Rheumatol., 1992, 4, pp. 325-331; M.H. Weisman, Curr. Opin. Rheumatol., 1995, 7, pp. 183-190; W. Sterry, Arch. Dermatol. Res., 1992, 284 (Suppl.), pp. S27-S29). While therapeutically beneficial, however, the use of corticosteroids is associated with a number of side effects, ranging from mild to possibly life threatening, especially with prolonged and/or high dose steroid usage. Accordingly, methods and compositions that enable the use of a lower effective dosage of corticosteroids (referred to as the "steroid sparing effect") would be highly desirable to avoid unwanted side effects. The compounds of the invention provide such a steroid sparing effect by achieving the desired therapeutic effect while allowing the use of lower doses and less frequent administration of glucocorticoids or corticosteroids. Administration of the compounds of the invention, in pure form or in an appropriate pharmaceutical composition, can be carried out using any of the accepted modes of administration of pharmaceutical compositions. Thus, administration can be, for example, orally, buccally (e.g., sublingually), nasally, parenterally, topically, transdermally, vaginally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as, for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, preferably in unit dosage forms suitable for simple administration of precise dosages. The pharmaceutical compositions will generally include a conventional pharmaceutical carrier or excipient and a compound of the invention as the/an active agent, and, in addition, may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, diluents, vehicles, or combinations thereof. Such pharmaceutically acceptable excipients, carriers, or additives as well as methods of making pharmaceutical compositions for various modes or administration are well-known to those of skill in the art. The state of the art is evidenced, e.g., by Remington: The Science and Practice of Pharmacy, 20th Edition, A. Gennaro (ed.), Lippincott Williams & Wilkins, 2000; Handbook of Pharmaceutical Additives, Michael & Irene Ash (eds.), Gower, 1995; Handbook of Pharmaceutical Excipients, A.H. Kibbe (ed.), American Pharmaceutical Ass'n, 2000; H.C. Ansel and N. G. Popovish, Pharmaceutical Dosage Forms and Drug Delivery Systems, 5th ed., Lea and Febiger, 1990; each of which is incorporated herein by reference in their entireties to better describe the state of the art.
As one of skill in the art would expect, the forms of the compounds of the invention utilized in a particular pharmaceutical formulation will be selected (e.g., salts) that possess suitable physical characteristics (e.g., water solubility) that is required for the formulation to be efficacious.
Pharmaceutical compositions suitable for buccal (sub-lingual) administration include lozenges comprising a compound of the present invention in a flavored base, usually sucrose, and acacia or tragacanth, and pastilles comprising the compound in an inert base such as gelatin and glycerin or sucrose and acacia. Pharmaceutical compositions suitable for parenteral administration comprise sterile aqueous preparations of a compound of the present invention. These preparations are preferably administered intravenously, although administration can also be effected by means of subcutaneous, intramuscular, or intradermal injection. Injectable pharmaceutical formulations are commonly based upon injectable sterile saline, phosphate-buffered saline, oleaginous suspensions, or other injectable carriers known in the art and are generally rendered sterile and isotonic with the blood. The injectable pharmaceutical formulations may therefore be provided as a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, including 1,3-butanediol, water, Ringer's solution, isotonic sodium chloride solution, fixed oils such as synthetic mono- or diglycerides, fatty acids such as oleic acid, and the like. Such injectable pharmaceutical formulations are formulated according to the known art using suitable dispersing or setting agents and suspending agents. Injectable compositions will generally contain from 0.1 to 5% w/w of a compound of the invention.
Solid dosage forms for oral administration of the compounds include capsules, tablets, pills, powders, and granules. For such oral administration, a pharmaceutically acceptable composition containing a compound(s) of the invention is formed by the incorporation of any of the normally employed excipients, such as, for example, pharmaceutical grades of mannitol, lactose, starch, pregelatinized starch, magnesium stearate, sodium saccharine, talcum, cellulose ether derivatives, glucose, gelatin, sucrose, citrate, propyl gallate, and the like. Such solid pharmaceutical formulations may include formulations, as are well known in the art, to provide prolonged or sustained delivery of the drug to the gastrointestinal tract by any number of mechanisms, which include, but are not limited to, pH sensitive release from the dosage form based on the changing pH of the small intestine, slow erosion of a tablet or capsule, retention in the stomach based on the physical properties of the formulation, bioadhesion of the dosage form to the mucosal lining of the intestinal tract, or enzymatic release of the active drug from the dosage form.
Liquid dosage forms for oral administration of the compounds include emulsions, microemulsions, solutions, suspensions, syrups, and elixirs, optionally containing pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, ethanol and the like. These compositions can also contain additional adjuvants such as wetting, emulsifying, suspending, sweetening, flavoring, and perfuming agents.
Topical dosage forms of the compounds include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, eye ointments, eye or ear drops, impregnated dressings and aerosols, and may contain appropriate conventional additives such as preservatives, solvents to assist drug penetration and emollients in ointments and creams. Topical application may be once or more than once per day depending upon the usual medical considerations. Furthermore, preferred compounds for the present invention can be administered in intranasal form by topical use of suitable intranasal vehicles. The formulations may also contain compatible conventional carriers, such as cream or ointment bases and ethanol or oleyl alcohol for lotions. Such carriers may be present as from about 1% up to about 98% of the formulation, more usually they will form up to about 80% of the formulation.
Transdermal administration is also possible. Pharmaceutical compositions suitable for transdermal administration can be presented as discrete patches adapted to remain in intimate contact with the epidermis of the recipient for a prolonged period of time. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen. Such patches suitably contain a compound of the invention in an optionally buffered, aqueous solution, dissolved and/or dispersed in an adhesive, or dispersed in a polymer. A suitable concentration of the active compound is about 1% to 35%, preferably about 3% to 15%.
For administration by inhalation, the compounds of the invention are conveniently delivered in the form of an aerosol spray from a pump spray device not requiring a propellant gas or from a pressurized pack or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, tetrafluoroethane, heptafluoropropane, carbon dioxide, or other suitable gas. In any case, the aerosol spray dosage unit may be determined by providing a valve to deliver a metered amount so that the resulting metered dose inhaler (MDI) is used to administer the compounds of the invention in a reproducible and controlled way. Such inhaler, nebulizer, or atomizer devices are known in the art, for example, in PCT International Publication Nos. WO 97/12687 (particularly Figure 6 thereof, which is the basis for the commercial RESPIMAT® nebulizer); WO 94/07607; WO 97/12683; and WO 97/20590, to which reference is hereby made and each of which is incorporated herein by reference in their entireties.
Rectal administration can be effected utilizing unit dose suppositories in which the compound is admixed with low-melting water-soluble or insoluble solids such as fats, cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights, or fatty acid esters of polyethylene glycols, or the like. The active compound is usually a minor component, often from about 0.05 to 10% by weight, with the remainder being the base component.
In all of the above pharmaceutical compositions, the compounds of the invention are formulated with an acceptable carrier or excipient. The carriers or excipients used must, of course, be acceptable in the sense of being compatible with the other ingredients of the composition and must not be deleterious to the patient. The carrier or excipient can be a solid or a liquid, or both, and is preferably formulated with the compound of the invention as a unit- dose composition, for example, a tablet, which can contain from 0.05% to 95% by weight of the active compound. Such carriers or excipients include inert fillers or diluents, binders, lubricants, disintegrating agents, solution retardants, resorption accelerators, absorption agents, and coloring agents. Suitable binders include starch, gelatin, natural sugars such as glucose or β-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. Lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrators include starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
Generally, a therapeutically effective daily dose is from about 0.001 mg to about 15 mg/kg of body weight per day of a compound of the invention; preferably, from about 0.1 mg to about 10 mg/kg of body weight per day; and most preferably, from about 0.1 mg to about 1.5 mg/kg of body weight per day. For example, for administration to a 70 kg person, the dosage range would be from about 0.07 mg to about 1050 mg per day of a compound of the invention, preferably from about 7.0 mg to about 700 mg per day, and most preferably from about 7.0 mg to about 105 mg per day. Some degree of routine dose optimization may be required to determine an optimal dosing level and pattern. Pharmaceutically acceptable carriers and excipients encompass all the foregoing additives and the like.
Examples of Pharmaceutical Formulations
Figure imgf000208_0001
The finely ground active substance, lactose, and some of the corn starch are mixed together. The mixture is screened, then moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet-granulated and dried. The granules, the remaining corn starch and the magnesium stearate are screened and mixed together. The mixture is compressed to produce tablets of suitable shape and size.
Figure imgf000208_0002
The finely ground active substance, some of the corn starch, lactose, macrocrystalline cellulose, and polyvinylpyrrolidone are mixed together, the mixture is screened and worked with the remaining corn starch and water to form a granulate which is dried and screened. The sodium- carboxymethyl starch and the magnesium stearate are added and mixed in and the mixture is compressed to form tablets of a suitable size.
Figure imgf000209_0001
The active substance, corn starch, lactose, and polyvinylpyrrolidone are thoroughly mixed and moistened with water. The moist mass is pushed through a screen with a 1 mm mesh size, dried at about 45°C and the granules are then passed through the same screen. After the magnesium stearate has been mixed in, convex tablet cores with a diameter of 6 mm are compressed in a tablet-making machine. The tablet cores thus produced are coated in known manner with a covering consisting essentially of sugar and talc. The finished coated tablets are polished with wax.
Figure imgf000209_0002
The substance and corn starch are mixed and moistened with water. The moist mass is screened and dried. The dry granules are screened and mixed with magnesium stearate. The finished mixture is packed into size 1 hard gelatine capsules.
Figure imgf000210_0001
The active substance is dissolved in water at its own pH or optionally at pH 5.5 to 6.5 and sodium chloride is added to make it isotonic. The solution obtained is filtered free from pyrogens and the filtrate is transferred under aseptic conditions into ampoules which are then sterilized and sealed by fusion. The ampoules contain 5 mg, 25 mg, and 50 mg of active substance.
Figure imgf000210_0002
The hard fat is melted. At 4O0C, the ground active substance is homogeneously dispersed therein. The mixture is cooled to 38°C and poured into slightly chilled suppository molds.
Figure imgf000210_0003
The suspension is transferred into a conventional aerosol container with a metering valve. Preferably, 50 μL of suspension are delivered per spray. The active substance may also be metered in higher doses if desired (e.g., 0.02% by weight).
Figure imgf000211_0001
Figure imgf000211_0002
Figure imgf000211_0003
Figure imgf000211_0004
In Examples H, I, J, and K, the powder for inhalation is produced in the usual way by mixing the individual ingredients together.
Figure imgf000212_0001
l-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol
1 -(4-Chloro-3 -methylphenyl)-2,2,2- trifluoro-l-(l-phenyl-lH-indazol-5- yl)ethanol
1 -(3-Chlorophenyl)-2,2,2-trifluoro- 1 -( 1 - phenyl- 1 H-indazol-5-yl)ethanol
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro- l-(l-phenyl-lH-indazol-5-yl)ethanol
Figure imgf000213_0001
Figure imgf000214_0001
Figure imgf000215_0001
Figure imgf000216_0001
Figure imgf000217_0001
Figure imgf000218_0001
2,2,2-Trifluoro- 1 -(3-fluoro-4- methoxyphenyl)-l-(l-phenyl-lH-indazol-5- yl)ethanol
2,2,2-Trifluoro-l-(5-fluoro-2- methoxyphenyl)- 1 -(I -phenyl- lH-indazol-5- yl)ethanol
1 -(2,5-Dimethoxyphenyl)-2,2,2-trifluoro- 1 - (1 -phenyl- lH-indazol-5-yl)ethanol
2,2,2-Trifluoro- 1 -(2-morpholin-4- ylmethylphenyl)- 1 -(I -phenyl- lH-indazol-5- yl)ethanol
Figure imgf000219_0001
Figure imgf000220_0001
Figure imgf000221_0001
Figure imgf000222_0001
Figure imgf000223_0001
Figure imgf000224_0001
Figure imgf000225_0001
Figure imgf000226_0001
Figure imgf000227_0001
Figure imgf000228_0001
Figure imgf000229_0001
Figure imgf000230_0001
Figure imgf000231_0001
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl- lH-indazol-5-yl)ethyl]quinoline-3- carboxylic acid ethyl ester
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5- yl)-l-quinolin-4-ylethanol
2,2,2-Trifluoro- 1 -(2-methylquinolin-4-yl)- 1 - (l-phenyl-lH-indazol-5-yl)ethanol
2,2,2-Trifluoro- 1 -isoquinolin- 1 -yl- 1 -( 1 - phenyl-lH-indazol-5-yl)ethanol
Figure imgf000232_0001
Figure imgf000233_0001
Figure imgf000234_0001
Figure imgf000235_0001
Figure imgf000236_0001
Figure imgf000237_0001
Figure imgf000238_0001
Figure imgf000239_0001
Figure imgf000240_0001
Figure imgf000241_0001
Figure imgf000242_0001
Figure imgf000243_0001
Figure imgf000244_0001
Figure imgf000245_0001
Figure imgf000246_0001
Figure imgf000247_0001
Figure imgf000248_0001
Figure imgf000249_0001
Figure imgf000250_0001
3-(4-Bromophenylsulfanyl)- 1,1,1 -trifluoro- 2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol
1,1,1 -Trifluoro-3 -(4-fluorophenylsulfanyl)- 2-(l-phenyl-lH-indazol-5-yl)propan-2-ol
l,l,l-Trifluoro-3-(2- isopropylphenylsulfanyl)-2-( 1 -phenyl- IH- indazol-5-yl)propan-2-ol
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5- yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol
Figure imgf000251_0001
1,1,1 -Trifluoro-3 -(4-nitrophenylsulfanyl)-2- ( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5- yl)-3-o-tolylsulfanylpropan-2-ol
l,l,l-Trifluoro-2-(l~phenyl-lH-indazol-5- yl)-3-m-tolylsulfanylpropan-2-ol
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5- yl)-3-p-tolylsulfanylpropan-2-ol
Figure imgf000252_0001
Figure imgf000253_0001
Figure imgf000254_0001
Figure imgf000255_0001
Figure imgf000256_0001
Figure imgf000257_0001
Figure imgf000258_0001
Figure imgf000259_0001
Figure imgf000260_0001
Figure imgf000261_0001
Figure imgf000262_0001
Figure imgf000263_0001
Figure imgf000264_0001
Figure imgf000265_0001
Figure imgf000266_0001
Figure imgf000267_0001
Figure imgf000268_0001
Figure imgf000269_0001
Figure imgf000270_0001
Figure imgf000271_0001
Figure imgf000272_0001
Figure imgf000273_0001
Figure imgf000274_0001
Figure imgf000275_0001
Figure imgf000276_0001
Figure imgf000277_0001
Figure imgf000278_0001
Figure imgf000279_0001
Figure imgf000280_0001
Figure imgf000281_0001
Figure imgf000282_0001
Figure imgf000283_0001
Figure imgf000284_0001
Figure imgf000285_0001
Figure imgf000286_0001
4-{2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l- hydroxyethyl } naphthalene- 1 -carboxylic acid methylamide
4- {2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-l- hydroxyethyl}naphthalene- 1 -carboxylic acid dimethylamide
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5 -yl] - 1 -(2-methylnaphthalen- 1 - yl)ethanol
Figure imgf000287_0001
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5 -yl] - 1 -(2-methoxynaphthalen- 1 - yl)ethanol
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]- 1 -(6-methoxynaphthalen-2- yl)ethanol
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]-l-naphthalen-2-ylethanol
Figure imgf000288_0001
Figure imgf000289_0001
Figure imgf000290_0001
Figure imgf000291_0001
Figure imgf000292_0001
Figure imgf000293_0001
Figure imgf000294_0001
Figure imgf000295_0001
Figure imgf000296_0001
Figure imgf000297_0001
Figure imgf000298_0001
Figure imgf000299_0001
Figure imgf000300_0001
Figure imgf000301_0001
Figure imgf000302_0001
Figure imgf000303_0001
Figure imgf000304_0001
Figure imgf000305_0001
Figure imgf000306_0001
Figure imgf000307_0001
Figure imgf000308_0001
Figure imgf000309_0001
Figure imgf000310_0001
Figure imgf000311_0001
Figure imgf000312_0001
Figure imgf000313_0001
Figure imgf000314_0001
Figure imgf000315_0001
Figure imgf000316_0001
Figure imgf000317_0001
Figure imgf000318_0001
Figure imgf000319_0001
Figure imgf000320_0001
Figure imgf000321_0001
Figure imgf000322_0001
3-(3-Dimethylaminomethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2-ol
3 -(3 -Dimethylaminomethyl-5 - methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4- fluorophenyl)-lH-indazol-5-yl]propan-2-ol
Figure imgf000323_0001
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)- 1 H-indazol-5-yl] -2-hydroxypropyl } - 1 H- indol-3-yl)acetic acid ethyl ester
Figure imgf000323_0002
Figure imgf000324_0001
Figure imgf000325_0001
Figure imgf000326_0001
Figure imgf000327_0001
Figure imgf000328_0001
Figure imgf000329_0001
Figure imgf000330_0001
Figure imgf000331_0001
Figure imgf000332_0001
Figure imgf000333_0001
Figure imgf000334_0001
Figure imgf000335_0001
Figure imgf000336_0001
Figure imgf000337_0001
3-(2,3-Dihydro- 1 ,4-benzoxazin-4-yl)-l , 1,1- trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]propan-2-ol
3-(3,4-Dihydro-lH-isoquinolin-2-yl)-l,l,l- trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]propan-2-ol
3-(3,4-Dihydro-2H-quinoxalin- 1 -yl)- 1,1,1- trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]propan-2-ol
Figure imgf000338_0001
Figure imgf000339_0001
Figure imgf000340_0001
Figure imgf000341_0001
Figure imgf000342_0001
Figure imgf000343_0001
Figure imgf000344_0001
Figure imgf000345_0001
Figure imgf000346_0001
Figure imgf000347_0001
Figure imgf000348_0001
Figure imgf000349_0001
Figure imgf000350_0001
Figure imgf000351_0001
Figure imgf000352_0001
Figure imgf000353_0001
Figure imgf000354_0001
Figure imgf000355_0001
Figure imgf000356_0001
Figure imgf000357_0001
Figure imgf000358_0001
Figure imgf000359_0001
Figure imgf000360_0001
Figure imgf000361_0001
N-Cyanomethyl-2-(3-{2,2,2-trifluoro-l-[l- (4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)acetamide
N-Carbamoylmethyl-2-(3-{2,2,2-trifluoro-l- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 - hydroxyethyl}indol-l-yl)acetamide
1 -Morpholin-4-yl-2-(3- {2,2,2-trifluoro-l -[I - (4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)ethanone
Figure imgf000362_0001
Figure imgf000363_0001
Figure imgf000364_0001
Figure imgf000365_0001
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -pyridin-2-yl- 1 H-indazol-5 -yl)ethanol
2,2,2-Trifluoro- 1 -[I -(2-fluorophenyl)- IH- indazol-5-yl]- 1 -phenylethanol
2,2,2-Trifluoro- 1 -[I -(2-fluorophenyl)- IH- indazol-5-yl]- 1 -naphthalen- 1 -ylethanol
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[I -(2-fluorophenyl)- lH-indazol-5- yljethanol
Figure imgf000366_0001
Figure imgf000367_0001
Figure imgf000368_0001
Figure imgf000369_0001
Figure imgf000370_0001
Figure imgf000371_0001
l-(7-Bromo-lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5- yl]ethanol
l-(5-Bromo-lH-indol-3-yl)-2,2,2-trifluoro- l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- IH- indazol-5-yl]-l-(5-methyl-lH-indol-3- yl)ethanol
Figure imgf000372_0001
Figure imgf000373_0001
Figure imgf000374_0001
2,2,2-Trifluoro-l-(6-fluoro-lH-indol-3-yl)- l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- IH- indazol-5-yl]- 1 -(5-methoxy- lH-indol-3- yl)ethanol
2,2,2-Trifluoro-l-(7-fluoro-lH-indol-3-yl)- 1 - [ 1 -(4-fluorophenyl)- lH-indazol-5 - yl]ethanol
Figure imgf000375_0001
Figure imgf000376_0001
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]-l-(l-methyl-lH-indol-3- yl)ethanol
1 -(6-Bromo- 1 -methyl- lH-indol-3 -yl)-2,2,2- trifluoro-l-[l-(4-fluorophenyl)-lH-indazol- 5-yl]ethanol
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4- fluorophenyl)- 1 H-indazol-5 -yl] - 1 - hydroxyethyl } - 1 H-indole-6-carbonitrile
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]- 1 -(I -methyl-β-pyridin-S-yl- lH-indol-3-yl)ethanol
Figure imgf000377_0001
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5 -yl] - 1 -( 1 -methyl-6-pyridin-4-yl- lH-indol-3-yl)ethanol
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]-l-(l-methyl-6-morpholin-4- yl-lH-indol-3-yl)ethanol
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4- fluorophenyl)- 1 H-indazol-5 -yl] - 1 - hydroxyethyl}-lH-indole-6-carboxylic acid methyl ester
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH- indazol-5-yl]-l-(6-furan-2-yl-l-methyl-lH- indol-3 -yl)ethanol
Figure imgf000378_0001
Figure imgf000379_0001
Figure imgf000380_0001
Figure imgf000381_0001
Figure imgf000382_0001
Figure imgf000383_0001
Figure imgf000384_0001
l,l,l-Trifluoro-3-(2- isopropylphenylsulfanyl)-2-(l-phenyl-lH- indazol-5-yl)propan-2-ol
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5- yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol
3 -(4-Ethylphenylsulfanyl)- 1 ,1,1 -trifluoro-2- (1 -phenyl- lH-indazol-5-yl)propan-2-ol
Figure imgf000385_0001
Figure imgf000386_0001
Figure imgf000387_0001
Figure imgf000388_0001
1 , 1 , l-Trifluoro-2-(l -phenyl-lH-indazol-5- yl)-3-(2,4,6-trichlorophenoxy)propan-2-ol
1 , 1 ,1 -Trifluoro-2-(l -phenyl- lH-indazol-5- yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol
Figure imgf000389_0001
Figure imgf000390_0001
Figure imgf000391_0001
Figure imgf000392_0001
Figure imgf000393_0001
Figure imgf000394_0001
Figure imgf000395_0001
Figure imgf000396_0001
Figure imgf000397_0001
Figure imgf000398_0001
Figure imgf000399_0001
Figure imgf000400_0001
Figure imgf000401_0001
Figure imgf000402_0001
Figure imgf000403_0001
Figure imgf000404_0001
Figure imgf000405_0001
Figure imgf000406_0001
Figure imgf000407_0001
Figure imgf000408_0001
Figure imgf000409_0001
Figure imgf000410_0001
Figure imgf000411_0001
Figure imgf000412_0001
Figure imgf000413_0001
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]-3-(2- methoxyphenylamino)propan-2-ol
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- IH- indazol-5-yl]-3-(3- methoxyphenylamino)propan-2-ol
Figure imgf000414_0001
Figure imgf000415_0001
Figure imgf000416_0001
1,1,1 -Trifluoro-2-[l-(4-fluorophenyl)-lH- indazol-5 -yl] -3 -(naphthalen-2- ylamino)propan-2-ol
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5 -yl] -3 -(2-methylquinolin- 8- ylamino)propan-2-ol
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH- indazol-5-yl]-3-
(methylphenylamino)propan-2-ol
Figure imgf000417_0001
Figure imgf000418_0001
Figure imgf000419_0001
Figure imgf000420_0001
Figure imgf000421_0001
Figure imgf000422_0001
Figure imgf000423_0001
Figure imgf000424_0001
Figure imgf000425_0001
Figure imgf000426_0001
Figure imgf000427_0001
Figure imgf000428_0001
Figure imgf000429_0001
Figure imgf000430_0001
Figure imgf000431_0001
Figure imgf000431_0002
(3-Chloro-4-fluorophenyl)cyclopropyl-(l- phenyl-lH-indazol-5-yl)methanol
Cyclopropylnaphthalen- 1 -yl-( 1 -phenyl- 1 H- indazol-5 -yl)methanol
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)-(l - phenyl-lH-indazol-5-yl)methanol
Cyclopropyl-[l-(4-fluorophenyl)-lH- indazol-5-yl]naphthalen-l-ylmethanol
Figure imgf000432_0001
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)- [ 1 - (4-fluorophenyl)- 1 H-indazol-5-yl]methanol
Cyclopropy 1- [ 1 -(4-fluorophenyl)- 1 H- indazol-5 -yl] quinolin-4-ylmethanol
Cyclopropyl-[l-(4-fluorophenyl)-lH- indazol-5 -yl] isoquinolin- 1 -ylmethanol
Figure imgf000433_0001
1 -Cyclopropyl- 1 -[ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]-2-phenylsulfanylethanol
1 -Cyclopropyl- 1 -[ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]-2-(4- fluoroρhenylsulfanyl)ethanol
1 -Cyclopropyl- 1 -[I -(4-fluorophenyl)- IH- indazol-5-yl]-2-(naphthalen- 1 -yloxy)ethanol
Figure imgf000434_0001
1 -Cyclopropyl-2-(3 ,5-difluorophenoxy)- 1 - [l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol
l-Cyclopropyl-2-(3-fluorophenylamino)-l- [l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol
1 -Cyclopropyl- 1 - [ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]-2-phenylaminoethanol
Figure imgf000435_0001
1 -Cyclopropyl- 1 - [ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]-2-p-tolylaminoethanol
2-(4-Chlorophenylamino)- 1 -cyclopropyl- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]ethanol
1 - {2-Cyclopropyl-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-2-hydroxyethyl}-lH- indole-3 -carbonitrile
Figure imgf000436_0001
Figure imgf000437_0001
1 -(4-Fluoronaphthalen- 1 -yl)- 1 -[ 1 -(4- fluorophenyl)-lH-indazol-5-yl]-2,2- dimethylpropan- 1 -ol
l-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-2,2- dimethyl- 1 -quinolin-4-ylpropan- 1 -ol
l-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-l- isoquinolin- 1 -yl-2,2-dimethylpropan- 1 -ol
Figure imgf000438_0001
Cyclopentylρhenyl-( 1 -p-tolyl- lH-indazol-5- yl)methanol
Cyclopentyl-(3 ,5-dichlorophenyl)-( 1 -p- tolyl- lH-indazol-5-yl)methanol
(3-Chloro-4-fluorophenyl)cycloρentyl-(l-p- tolyl- 1 H-indazol-5 -yl)methanol
Cyclohexylphenyl-( 1 -j?-tolyl- 1 H-indazol-5 - yl)methanol
Cyclohexyl-(3,5-dichlorophenyl)-(l-p-tolyl- lH-indazol-5-yl)methanol
(3-Chloro-4-fluorophenyl)cyclohexyl-(l:p- tolyl- lH-indazol-5-yl)methanol
Figure imgf000440_0001
Figure imgf000441_0001
Figure imgf000442_0001
Figure imgf000443_0001
1 -(I -Cyclohexyl- lH-indazol-5-yl)-2- methyl- 1 -naphthalen- 1 -ylpropan- 1 -ol
1 -(I -Cyclohexyl-lH-indazol-S-yl)- 1 -(4- fluoronaphthalen- 1 -yl)-2-methylpropan- 1 -ol
l-(l-Cyclohexyl-lH-indazol-5-yl)-2- methyl- 1 -quinolin-4-ylpropan- 1 -ol
( 1 -Cyclohexyl- 1 H-indazol-5 -yl)isoquinolin- 1 -ylphenylmethanol
Figure imgf000444_0001
1 -Cyclopropyl-2-phenyl- 1 -( 1 -phenyl- IH- indazol-5-yl)ethanol
1 -Cyclopropyl-2-(3,5-dichlorophenyl)- 1 -(I - phenyl-lH-indazol-5-yl)ethanol
1 -Cyclopropyl- 1 -( 1 -phenyl- lH-indazol-5- yl)-2-rø-tolylethanol
1 -Cyclopropyl- 1 -( 1 -phenyl- 1 H-indazol-5- yl)-2-p-tolylethanol
Figure imgf000445_0001
1 -Cyclopropyl-2-(3 -fluorophenyl)- 1 -( 1 - phenyl- 1 H-indazol-5-yl)ethanol
1 -Cyclopropyl- 1 - [ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]-3-phenylpropan- 1 -ol
l-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-2- m-tolylpropan-2-ol
2-Phenyl- 1 -(I -phenyl- lH-indazol-5- yl)propan-2-ol
Figure imgf000446_0001
1 -[I -(4-Fluorophenyl)- lH-indazol-5-yl]-2- methyl-3 -phenylpropan-2-ol
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)- [ 1 -
(4-fluorophenyl)-lH-benzotriazol-5- yl]methanol
Cyclopropyl- [ 1 -(4-fluorophenyl)- 1 H- benzotriazol-5 -yl] quinolin-4-ylmethanol
Figure imgf000447_0001
Cyclopropyl-[l-(4-fluorophenyl)-lH- benzotriazol-5-yl]isoquinolin-l-ylmethanol
Cyclopropylphenyl-( 1 -phenyl- IH- benzotriazol-5 -yl)methanol
Cyclopropyl-(4-fluoronaphthalen-l-yl)-[l-
(4-fluorophenyl)-lH-benzimidazol-5- yljmethanol
Figure imgf000448_0001
Cyclopropyl-[ 1 -(4-fluorophenyl)- IH- benzimidazol-5-yl]quinolin-4-ylmethanol
Cyclopropyl-[l-(4-fluorophenyl)-lH- benzimidazol-5-yl]isoquinolin-l-ylmethanol
Cyclopropylphenyl-(1 -phenyl- lH-indol-5- yl)methanol
Figure imgf000449_0001
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)-[ 1 - (4-fluorophenyl)-lH-indol-5-yl]methanol
Cyclopropyl-[l-(4-fluorophenyl)-lH-indol- 5 -yl] quinolin-4-ylmethanol
Cyclopropyl-[l-(4-fluorophenyl)-lH-indol- 5-yl] isoquinolin- 1 -ylmethanol
Figure imgf000450_0001
Figure imgf000451_0001
l-(l-Allyl-lH-indol-3-yl)-l-[l-(4- fluorophenyl)- lH-indazol-5-yl]propan- 1 -ol
Figure imgf000452_0001
or a tautomer, prodrug, solvate, or salt thereof.

Claims

We Claim:
1. A compound of Formula (IA)
Figure imgf000453_0001
wherein:
R1 is aryl, heteroaryl, or C3-C7 cycloalkyl each optionally independently substituted with one to three substituent groups selected from CpC3 alkyl, hydroxy, halogen, oxo, methoxy, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a methyl group; or thiomethyl wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;
R2 is hydrogen or a halogen;
A and B are each independently CH or N;
C and E are each independently a bond or a -CH2-;
D is -CR4R5-, where R4 is -CF3 and R5 is -OH; and
R3 is C1-Ce alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, NR6R7, OR8, or SR9, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently aryl, heteroaryl, heterocyclyl, C1-Cs alkyl, Q-C5 alkenyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, Ci-C5 alkanoyloxy, C1-C5 alkanoyl, aroyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, Ci-C5 alkylaminocarbonyloxy, Ci-C5 dialkylaminocarbonyloxy, Ci-C5 alkanoylamino, Ci-C5 alkoxycarbonylamino, Ci-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, carboxyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from aryl, heteroaryl, heterocyclyl, acyl, C1-C5 alkyl, C1-C5 alkanoyloxy, C1-Cs alkanoyl, C1-Cs alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, C1-C5 alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, C1-C5 dialkylaminosulfonyl, C1- C5 alkyloxy, C1-C5 cycloalkyl, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or C1-C3 alkyl, and
R7, R8, and R9 are each independently C1-C5 alkyl, C1-C5 alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl optionally independently substituted with one to three substituent groups,
wherein each substituent group of R7, R8, and R9 is independently heteroaryl, heterocyclyl, C1-C5 alkyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, C1-C5 alkanoyloxy, C1-C5 alkanoyl, aroyl, C1-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C1-C5 alkylaminocarbonyloxy, C1-C5 dialkylaminocarbonyloxy, C1-C5 alkanoylamino, C1-C5 alkoxycarbonylamino, Ci-C5 alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, C1-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein each substituent group of R7, R8, and R9 is optionally independently substituted with one to three substituent groups selected from heteroaryl, heterocyclyl, acyl, C1-C5 alkyl, C1-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, C1-C5 alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, C1-C5 dialkylaminosulfonyl, C1-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
2. The compound of Formula (IA) according to claim I5 wherein:
R1 is aryl or heteroaryl optionally independently substituted with one to three substituent groups selected from hydroxy, halogen, or oxo;
R2 is hydrogen; and
C is a bond and E is a bond or -CH2-,
or a tautomer, prodrug, solvate, or salt thereof.
3. The compound of Formula (IA) according to claim I5 wherein:
R1 is a phenyl optionally substituted with one to three halogen groups;
A is N;
B is CH; and
R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4- dihydro-2H- 1 ,4-benzoxazine, 1 ,2,3 ,4-tetrahydroisoquinoline, N-ethyl-JV - methylbenzene-l,2-diamine, 1,2,3,4-tetrahydroquinoline, NR6R7, OR8, or SR9 group, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently Ci-C5 alkyl, heteroaryl, heterocyclyl, acyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, C1-C5 alkenyl, carboxyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from heterocyclyl, Q-C5 alkyl, C1-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or a methyl group, and
R7, Rs, and R9 are each independently a phenyl, naphthyl, pyridyl, pyrimidyl, quinoline, isoquinoline, or indolyl optionally independently substituted with one to three substituent groups,
wherein each substituent group of R7, R8, and R9 is independently heterocyclyl, Ci-C5 alkyl, cycloalkyl, acyl, Ci-C5 alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Q- C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
4. The compound of Formula (IA) according to claim 3, wherein:
R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4- dihydro-2H-l,4-benzoxazine, 1,2,3,4-tetrahydroisoquinoline, N-ethyl-N5- methylbenzene-l,2-diamine, or 1,2,3,4-tetrahydroquinollne,
wherein each substituent group of R3 is independently C1-Cs alkyl, C1-Cs alkenyl, carboxyl, acyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from C1-C5 alkyl, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
5. A compound selected from:
l-Biphenyl-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3,5-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-methylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3-Chlorophenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(4-Chloro-3-fluorophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol; l-CS^-DichlorophenyO^^^-trifluoro-l-Cl-phenyl-lH-indazol-S-y^ethanol;
2,2,2-Trifluoro- 1 -(3 -fluorophenyl)- 1 -( 1 -phenyl- IH- indazol-5-yl)ethanol;
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5- yl)ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 - 1 ,3 -Benzodioxol-4-yl-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,2-Difluoro-l ,3-benzodioxol-4-yl)-2,2,2-trlfluoro- 1 -(I -phenyl- lH-indazol-5- yl)ethanol;
1 -(3,4-Dichlorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-fluorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(l-phenyl-lH-indazol-5-yl)-l-(2,4,5-trimethylphenyl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl-lH-indazol-5-yl)- 1 -(2,4,6-trimethylphenyl)ethanol;
1 -(4-tert-Butyl-2,6-dimethylphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-methoxyphenyl)- 1 -(I -phenyl- 1 H-indazol-5-yl)ethanol;
1 -(3,5-Dimethylphenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro-l-(4-methoxy-3,5-dimethylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3 ,4-Dimethylphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
,2,2-Trifluoro-l-(3-fluoro-4-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
,2,2-Trifluoro- 1 -(5-fluoro-2-methoxyphenyl)-l -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,5-Dimethoxyphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-morpholin-4-ylmethylphenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -(2-piperidin- 1 -ylmethylphenyl)ethanol;
2,2,2-Trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)- 1 -(3 -piperidin- 1 -ylmethylphenyl)ethanol;
l-Biphenyl-2-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -Biphenyl-4-yl-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(4-Chloro-2-methylphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,4-Dimethoxyphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
l-(3,4-Dimethoxyphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxy-5-methylphenyl)-l -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methoxy-2-methylphenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxyphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- l-(4-methoxy-3-methylphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro- 1 -(4-phenoxyphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-isopropylphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(2-methylsulfanylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-methylsulfanylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(2,3-Dimethylphenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,4-Dimethylphenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(2,5-Dimethylphenyl)-2,2,2-trifluoro-l -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(2,6-Dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Ethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(2-Ethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-fluorobiphenyl-4-yl)- 1 -(I -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-fluoro-2-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-fluoro-4-methylphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoro-2-methylphenyl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(5-fluoro-2-methylphenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoro-2-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -phenyl- 1 H-indazol-5-yl)ethanol; 2,2,2-Trifluoro- 1 -(4-methylnaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-nitronaphthalen-l -yl)- 1 -(I -phenyl-lH-indazol-5-yl)ethanol;
1 -(4- Aminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methylaminonaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
1 -(4-Dimethylaminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -(I -phenyl-lH-indazol-5- yl)ethanol;
4- [2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethyl]naphthalene- 1 -sulfonic acid amide;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]naphthalene-l-sulfonic acid methylamide;
4-[2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -phenyl- lH-indazol-5-yl)ethyl]naphthalene- 1 -sulfonic acid dimethylamide;
4-[2,2,2-Trifluoro- 1 -hydroxy- 1 -(I -phenyl- lH-indazol-5-yl)ethyl]naphthalene- 1 - carbonitrile;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]naphthalene-l- carboxylic acid amide;
4-[2,2,2-Trifluoro- 1 -hydroxy- 1 -(1-phenyl- lH-indazol-5-yl)ethyl]naphthalene- 1 - carboxylic acid methylamide;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]naphthalene-l- carboxylic acid dimethylamide;
2,2,2-Trifluoro- 1 -(2-methylnaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro- 1 -(2-methoxynaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(6-methoxynaphthalen-2-yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen-2-yl- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]quinoline-3-carboxylic acid dimethylamide;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]quinoline-3-carboxylic acid methylamide;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]quinoline-3-carboxylic acid amide;
4-[2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethyl]quinoline-3 -carboxylic acid ethyl ester;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro-l-(2-methylquinolin-4-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -isoquinolin- 1 -yl- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-isoquinolin-4-yl-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-methylpyridin-2-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-methylpyridin-2-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(5-methylpyridin-2-yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(6-methylpyridin-2-yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -ρyridin-2-ylethanol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(lH-indol-4-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(lH-indol-3-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 , 1 , l-Trifluoro-3-(lH-indol-2-yl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-indol- 1 -yl-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1 - [3 ,3 ,3 -Trifluoro-2-hydroxy-2-( 1 -phenyl- 1 H-indazol-5 -yl)propyl] - 1 H-indole-3 - carbonitrile;
l,l,l-Trifluoro-3-moφholin-4-yl-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-piperidin-l -ylpropan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-piperazin-l-ylpropan-2-ol;
3-(2,3-Dihydrobenzo[l ,4]oxazin-4-yl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
3 -(3 ,4-Dihydro- 1 H-isoquinolin-2-yl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3-(3,4-Dihydro-2H-quinoxalin-l -yl)-l ,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3 -(3 ,4-Dihydro-2H-quinolin- 1 -yl)- 1 ,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
1,1,1 -Trifluoro-3 -(3 -fluorophenyl)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol; l,l,l-Trifluoro-3-phenyl-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-phenyl-3 -(I -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
2-Benzyl- 1,1,1 -trifluoro-3-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-4-phenyl-2-( 1 -phenyl- lH-indazol-5-yl)butan-2-ol;
3-(2,3-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1 , 1 , l-Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-3-(naphthalen- 1 -ylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-thiophen-2-ylpyrimidin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-phenylpyrimidin-2-ylsulfanyl)propan- 2-ol;
3-[4-(4-Chlorophenyl)pyrimidin-2-ylsulfanyl]- 1 ,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol;
6-Methyl-2- [3,3,3 -trifluoro-2-hydroxy-2-( 1 -phenyl- 1 H-indazol-5 -yl)propylsulfanyl] -4- trifluoromethylnicotinonitrile;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(5-trifluoromethylpyridin-2- ylsulfanyl)propan-2-ol;
3 -(2-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan- 2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4- trifluoromethoxyphenylsulfanyl)propan-2-ol; 3-(4-Bromo-2-trifluoromethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-methoxyphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(quinolin-2-ylsulfanyl)propan-2-ol;
3-(4-Chlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(pyrimidin-2-ylsulfanyl)propan-2-ol;
3-(4,6-Dimethylpyrimidin-2-ylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
3 -(3 ,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(pyridin-4-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3 -(3 -methoxyphenylsulfanyl)-2-( 1 -phenyl- lH-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-methoxyphenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(3 -Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -y l)propan-2-ol;
3-(3,4-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-3 -(naphthalen-2-ylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(2-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(3 -fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dimethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2- ol;
3-(2,4-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
2-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]benzoic acid methyl ester;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(4-trifluoromethylpyrimidin-2- ylsulfanyl)propan-2-ol;
3-(3,5-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,5-Bis-trifluoromethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5- yl)propan-2-ol;
3-(2,4-Difluorophenylsulfanyl)- 1 , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-isopropylphenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol; l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2-trifluoromethylphenylsulfanyl)propan- 2-ol;
3-(3,4-Difluorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(3 -Ethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol ;
3-(4-te?t-Butylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propylsulfanyl]phenyl}acetamide;
3-(4-Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-nitrophenylsulfanyl)-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-o-tolylsulfanylpropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-/w-tolylsulfanylpropan-2-ol;
1 , 1 ,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-p-tolylsulfanylpropan-2-ol;
3-(3-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan- 2-ol;
3 -(3 ,4-Dimethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol; 3 -(5 -tert-Butyl-2-methylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trimethylphenylsulfanyl)propan-2- ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-3-(4-methylsulfanylphenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan- 2-61;
3-(2-Chloro-6-methylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5- yl)propan-2-ol;
3-(2-tert-Butylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylpyridin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(3- trifluoromethoxyphenylsulfanyl)propan-2-ol;
3-(3,5-Dimethylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2,3,6-trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,3,5-trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(quinolin-7-yloxy)propan-2-ol;
5-Chloro-2-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy]benzonitrile;
1,1,1 -Trifluoro-3-(3-moφholin-4-ylphenoxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol; -(3-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(quinolin-5-yloxy)propan-2-ol;
-(2-Bromophenoxy)- 1 ,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propoxy]benzonitrile;
, 1 ,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenoxy)propan-2-ol;
-(2-Chloro-5-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4-trifluoromethylphenoxy)propan-2-ol;
,1,1 -Trifluoro-3-(naphthalen-2-yloxy)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
-(4-Chlorophenoxy)- 1 ,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
-(3,5-Difluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3 -(2-trifluoromethylphenoxy)propan-2-ol;
-(2,4-Difluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(quinolin-8-yloxy)propan-2-ol;
-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
-(2,5-Difluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; 3-(4-Chloro-2-fluorophenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluoro-2-methylphenoxy)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2,3,4-trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-6-methoxyphenoxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2- ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,3,6-trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trifluorophenoxy)propan-2-ol;
2-Chloro-4-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy]benzonitrile;
3-(2-Chloro-3,5-difluorophenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
1,1,1 -Trifluoro-3 -(7-methoxynaphthalen-2-yloxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3 -(2-Bromo-5 -fluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol ;
5-Acetyl-2-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propoxy]benzoic acid methyl ester;
2-Fluoro-4-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propoxy]benzonitrile;
1,1,1 -Trifluoro-3-(2-fluoro-5-trifluoromethylphenoxy)-2-(l -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
3-(4-Bromo-3-methylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-5-methylphenoxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol; N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy]phenyl } butyramide ;
3-(5-Chloro-2-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-methylsulfanylphenoxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-o-tolyloxypropan-2-ol;
1 , 1 ,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-/«-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l-phenyl- lH-indazol-5-yl)-3-p-tolyloxypropan-2-ol;
3 - [3 ,3 ,3 -Trifluoro-2-hydroxy-2-( 1 -phenyl- 1 H-indazol-5 -yl)propoxy]benzonitrile ;
4-[3 ,3 ,3 -Trifluoro-2-hydroxy-2-( 1 -phenyl- lH-indazol-5-yl)propoxy]benzonitrile;
3-(2,4-Dimethylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dimethylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(3 -fluorophenoxy)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-fluorophenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(isoquinolin-5-yloxy)-2-( 1 -phenyl-lH-indazol-5-yl)propan-2-ol; 1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)-3-(2,4,6-trichlorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-3-(6-methoxynaphthalen-2-yloxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2- ol;
1,1,1 -Trifluoro-3-(naphthalen- 1 -yloxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l-{3,5-Difluoro-4-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy]phenyl } ethanone ;
1,1,1 -Trifluoro-3-(isoquinolin-7-yloxy)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2-trifluoromethoxyphenoxy)propan-2-ol;
1,1,1 -Trifluoro-3-(4-phenylaminophenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3 -Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluoro-5-trifluoromethylphenoxy)-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-methylsulfanylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Dimethylaminomethylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan- 2-ol;
5-Bromo-2-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy]benzonitrile;
3 -(4-Chloro-3 -trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5 - yl)propan-2-ol; 3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2- ol;
3-(2-Dimethylaminomethylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3-(2,6-Dichloro-4-methylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol;
3 -Methoxy-4-[3 ,3 ,3 -trifluoro-2-hydroxy-2-(l -phenyl- 1 H-indazol-5-yl)propoxy]benzoic acid ethyl ester;
4- [3 ,3 ,3 -Trifluoro-2-hydroxy-2-( 1 -phenyl- 1 H-indazol-5 -yl)propoxy]benzoic acid methyl ester;
l,l,l-Trifluoro-3-(4-imidazol-l-ylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy] phenyl } acetamide;
3-(3-Dimethylaminophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l-(4-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propoxy]phenyl}piperazin- 1 -yl)ethanone;
1,1,1 -Trifluoro-3-(2-methyl-3H- 1 D 4-benzothiazol-5-yloxy)-2-( 1 -phenyl- 1 H-indazol-5- yl)propan-2-ol;
3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(3 -methoxy-5 -trifluoromethylphenylamino)-2-( 1 -phenyl- 1 H-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(naphthalen- 1 -ylamino)-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol; 4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylamino]naphthalene-l- carbonitrile;
3 -(4-Chloronaphthalen- 1 -ylamino)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
l,l,l-Trifluoro-3-(naphthalen-2-ylamino)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l-Biphenyl-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(4-fluoro-3-oxazol-5-ylphenyl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}benzonitrile;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}benzamide;
N^N-Dimethyl-4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}benzamide;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(3,5-Difluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]ethanol;
l-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-(4-Chloro-3-methylphenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l -[I -(4-fluorophenyl)-l H-indazol-5 - yljethanol; l-(4-Chloro-3-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-CS^-DichlorophenyO^^^-trifluoro-l-fl-C^fluorophenyO-lH-indazol-S-y^ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(4-fluorophenyl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-(3-fluoro-4-methylphenyl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -(3-fluorophenyl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
l-(4-Chlorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)-l -[I -(4-fluorophenyl)- lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(4-methylnaphthalen-l - yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]-l -(4-nitronaphthalen- 1 - yl)ethanol;
1 -(4-Aminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] - 1 -(4-methylaminonaphthalen- 1 - yl)ethanol; l-(4-Dimethylaminonaphthalen-l-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}naphthalene- 1 -sulfonic acid amide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}naphthalene- 1 -sulfonic acid methylamide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}naphthalene- 1 -sulfonic acid dimethylamide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}naphthalene- 1-carbonitrile;
4- {2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl }naphthalene- 1-carboxylic acid amide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}naphthalene- 1-carboxylic acid methylamide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}naphthalene- 1-carboxylic acid dimethylamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(2-methylnaphthalen-l- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(2-methoxynaphthalen- 1 - yl)ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -(6-methoxynaphthalen-2- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-2-ylethanol; 4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}quinoline-3- carboxylic acid dimethylamide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}quinoline-3- carboxylic acid methylamide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}quinoline-3- carboxylic acid amide;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}quinoline-3- carboxylic acid ethyl ester;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 - [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(2-methylquinolin-4-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]-l -isoquinolin-1 -ylethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-isoquinolin-4-ylethanol;
1 -(2,3-Dihydrobenzo[l ,4]dioxin-6-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol- 5-yl]ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-Benzofuran-5-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-Benzofuran-2-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-4-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-4- yl)ethanol; l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1,1,1 -Trifluoro-3-(3-fluorophenyl)-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-phenylpropan-2-ol;
1,1,1 -Trifluoro-3-[l -(4-fluorophenyl)- lH-indazol-5-yl]-2-phenylpropan-2-ol;
2-Benzyl- 1,1,1 -trifluoro-3-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-methoxy-5- trifluoromethylphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(naphthalen- 1 -ylamino)propan- 2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino }naphthalene- 1 -carbonitrile;
3-(4-Chloronaphthalen- 1 -ylamino)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazo 1-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5 -yl] -3 -(naphthalen-2-ylamino)propan- 2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-morpholin-4- ylphenylamino)propan-2-ol ;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-5-ylamino)propan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(quinolin-6-ylamino)propan-2- ol; 3 -(2,3 -Dihydro- 1 ,4-benzodioxin-6-ylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H- indazol-5-yl]propan-2-ol;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(isoquinolin-5-ylamino)propan- 2-ol;
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino } benzonitrile ;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trifluorophenylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-fluoro-5- trifluoromethylphenylamino)propan-2-ol;
3-(2,6-Difluorophenylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol;
3-(2-Chlorophenylamino)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trichlorophenylamino)propan-2-ol;
3-(2,5-Dichlorophenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(2,6-Dichlorophenylamino)- 1,1,1 -trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3 -(Biphenyl-2-ylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-o-tolylaminopropan-2-ol; l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-methoxy-2- methylphenylamino)propan-2-ol;
3-(2,4-Dimethylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trimethylphenylamino)propan-2-ol;
1 , 1 , 1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trimethylphenylamino)propan-2-ol;
3 -(2,6-Dimethylphenylamino)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(2-Ethyl-6-methylphenylamino)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}benzonitrile;
3-(3-Bromophenylamino)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
3 -(3 -Chlorophenylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5 -yljpropan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3- methylsulfanylphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3- trifluoromethylphenylamino)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-ra-tolylaminopropan-2-ol; 3-(3,5-Dimethylphenylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino } benzonitrile;
3-(4-Chlorophenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
3-(4-Dimethylaminophenylamino)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- IH- indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- phenoxyphenylatnino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- methylsulfanylphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- isopropylphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-p-tolylaminopropan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino } benzenesulfonamide ;
3-(2,4-Dimethoxyphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3 -(3 ,5 -Dimethoxyphenylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
3-(4,5-Dimethoxy-2-methylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH- indazol-5-yl]propan-2-ol; 3-(Benzothiazol-6-ylamino)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
2-Chloro-6-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino } benzonitrile ;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}benzoic acid methyl ester;
5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino } benzonitrile ;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-methylquinolin-8- ylamino)propan-2-ol;
N^V-Dimethyl-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}benzenesulfonamide;
2-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino } benzonitrile ;
4-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino }benzonitrile;
1,1,1 -Trifluoro-3 -(2-fluoro-4-rnethylphenylamino)-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- trifluoromethoxyphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3- trifluoromethoxyphenylamino)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methoxy-5- trifluoromethylphenylamino)propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-methoxy-3- trifluoromethylphenylamino)propan-2-ol;
3-(2,4-Dichloro-6-methylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol- 5-yl]propan-2-ol;
3 -(B iphenyl-3 -ylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(4-piperidin- 1 - ylphenylamino)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-oxazol-5- ylphenylamino)propan-2-ol;
3-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}benzonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-pyridin-4- ylmethylphenylamino)propan-2-ol;
2-Methyl-6-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}benzonitrile;
3-(4-Chloro-2,6-dimethylphenylamino)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol- 5-yl]propan-2-ol;
3 -(Benzoxazol-6-ylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methylnaphthalen-l - ylamino)propan-2-ol; 3-(Biphenyl-4-ylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -3 -(3 - phenoxyphenylamino)propan-2-ol;
3 -(3 -Chloro-2-methylphenylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
3-(2-Chloro-5-trifluoromethylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH- indazol-5-yl]propan-2-ol;
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino} benzoic acid methyl ester;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}phenyl)acetamide;
5- { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -2-hydroxypropylamino } - 1 ,3 - dihydrobenzimidazol-2-one;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]-3-indol-l -ylpropan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-pyrrolo[2,3-δ]pyridin-l- ylpropan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypiOpyl}-lH-indole- 2-carboxylic acid ethyl ester;
3-(2,3-Dimethylindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3 -(5 -Chloro-2-methylindol- 1 -yl)- 1 , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5 - yl]propan-2-ol; l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 3-carbonitrile;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -y 1] -3 -(5 -methoxy-2-methylindol- 1 - yl)propan-2-ol;
3-(2,5-Dimethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
l-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3 -yl)ethanone ;
3 -(3 -Dimethylaminomethylindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol- 5-yl]propan-2-ol;
3 -(3-Dimethylaminomethyl-5-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol;
( 1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indol- 3-yl)acetic acid ethyl ester;
2-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3-yl)acetamide;
3-(4-Chloroindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3 -(5-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-3-(5-fluoroindol-l -yl)-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
3-(5-Chloroindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5-nitroindol-l -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(5 -methoxyindol- 1 -yl)pf opan- 2-ol;
3 -(5,6-Dimethoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(6-Chloroindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-nitroindol-l -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-methoxyindol-l -yl)propan- 2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(4-nitroindol- 1 -yl)propan-2-ol;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 6-carbonitrile;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxyindol-l -yl)propan- 2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,7-trimethylindol-l - yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluoroindol-l -yl)-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-3 -(5-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2- ol; l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methyl-5-nitroindol-l- yl)propan-2-ol;
4-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indole-2-carboxylic acid methyl ester;
6-Methoxy- 1 - { 3 ,3 ,3 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - lH-indole-2-carboxylic acid methyl ester;
3-(7-Ethylindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 5-carboxylic acid methyl ester;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 3-carboxylic acid methyl ester;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 4-carboxylic acid methyl ester;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 6-carboxylic acid methyl ester;
3 -(6-Bromoindol- 1 -yl)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(6-trifluoromethylindol- 1 - yl)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -3 -(3 -methoxymethylindol- 1 - yl)propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 2-carboxylic acid methyl ester; 3-(4-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3 -(7-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
l,l,l-Trifluoro-3-(7-fluoroindol-l-yl)-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
3-(3-Dimethylaminomethyl-6-methoxyindol- 1 -yl)- 1 ,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol;
3-(7-Chloroindol-l-yl)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3-(7-Bromo-2-methylindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
(5-Methoxy- 1 - { 3 ,3 ,3 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indol-3 -yl)acetonitrile ;
5-Chloro-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indole-2-carboxylic acid ethyl ester;
5-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indole-2-carboxylic acid ethyl ester;
5 -Methyl- 1 - { 3 ,3 ,3 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - lH-indole-2-carboxylic acid ethyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-morpholin-4-ylpropan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-piperidin- 1 -ylpropan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-piperazin- 1 -ylpropan-2-ol; 3-(2,3-Dihydro-l,4-benzoxazin-4-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(3,4-Dihydro-lH-isoquinolin-2-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(3,4-Dihydro-2H-quinoxalin- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(3,4-Dihydro-2H-quinolin-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -phenyl- 1 H-benzotriazol-5-yl)ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-benzotriazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-benzotriazol-5-yl]- 1 -naphthalen-1 -ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen-l -yl)-l -[I -(4-fluorophenyl)- lH-benzotriazol-5- yljethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-phenyl-lH-benzimidazol-5-yl)ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-benzimidazol-5- yljethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-benzimidazol-5-yl]-l -naphthalen- 1 -ylethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-[l-(4-fluorophenyl)-lH-benzimidazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -phenyl- lH-indol-5-yl)ethanol; l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-flιιorophenyl)-lH-indol-5-yl]-l-naphthalen-l-ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[ 1 -(4-fluorophenyl)- 1 H-indol-5-yl]ethanol;
l-(3-Chloro-4-fluorophenyl)-l-[l-(4-dimethylaminophenyl)-lH-indazol-5-yl]-2,2,2- trifluoroethanol;
l-[l-(4-Dimethylaminophenyl)-lH-indazol-5-yl]-2,2,2-trifluoro-l-naphthalen-l- ylethanol;
l-[l-(4-Dimethylaminophenyl)-lH-indazol-5-yl]-2,2,2-trifluoro-l-(4-fluoronaphthalen-l- yl)ethanol;
4- { 5-[ 1 -(3 -Chloro-4-fluorophenyl)-2,2,2-trifluoro- 1 -hydroxyethyl] indazol- 1 -yl}phenol;
4-[5-(2,2,2-Trifluoro- 1 -hydroxy- 1 -naphthalen- 1 -ylethyl)indazol- 1 -yl]phenol;
4-{5-[2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-hydroxyethyl]indazol-l-yl}phenol;
1 -(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro- 1 -[I -(4-methoxyphenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -[I -(4-methoxyphenyl)- lH-indazol-5-yl]- 1 -naphthalen- 1 -ylethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-[l-(4-methoxyphenyl)-lH-indazol-5- yl]ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(3-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(3-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol; 2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 - [ 1 -(3 -fluorophenyl)- lH-indazol-5 - yl]ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethanol;
1 -(3-Chloro-4-fluorophenyl)-l -[ 1 -(4-chloroρhenyl)- lH-indazol-5-yl]-2,2,2- trifluoroethanol;
1 -[l-(4-Chlorophenyl)- lH-indazol-5-yl]-2,2,2-trifluoro- 1 -naphthalen- 1 -ylethanol;
1 -[I -(4-Chlorophenyl)- lH-indazol-5-yl]-2,2,2-trifluoro- 1 -(4-fluoronaphthalen- 1 - yl)ethanol;
1 -(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l -(I -pyridin-2-yl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -pyridin-2-yl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -(I -pyridin-2-yl- 1 H-indazol-5-yl)ethanol;
1 -(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro- 1 -(I -pyridin-4-yl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -pyridin-4-yl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -(I -pyridin-4-yl- lH-indazol-5-yl)ethanol;
1 -(3-Chloro-4-fluorophenyl)- 1 -( 1 -cyclohexyl- lH-indazol-5-yl)-2,2,2-trifluoroethanol;
l-(l-Cyclohexyl-lH-indazol-5-yl)-2,2,2-trifluoro-l-naphthalen-l-ylethanol;
1 -( 1 -Cyclohexyl- lH-indazol-5-yl)-2,2,2-trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)ethanol; 2,2,2-Trifluoro-l-(6-fluoropyridin-2-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
3-(3-Chloro-2 -fluorophenyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-fluorophenyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(4-Chloro-2-fluorophenyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1 -(2,2-Difluoro- 1 ,3-benzodioxol-4-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol- 5-yl]ethanol;
1-1 ,3-Benzodioxol-4-yl-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(lH-indol-7-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-7- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-5- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl- lH-indol-6- yl)ethanol;
4-{2,2,2-Trlfluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indole-l- carboxylic acid ter/-butyl ester;
l-(3-Aminophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
N-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenyl}acetamide;
l-Methyl-4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- quinolin-2-one;
l-(l-Allyl-lH-indol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol; 3-(4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)propane- 1 ,2-diol;
3-Ηydroxy-4-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)butyronitrile;
2,2,2-Trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -[I -(2-hydroxyethyl)-lH-indol- 4-yl]ethanol;
2-(4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-liydroxyethyl}indol-l- yl)acetamide;
N-Methyl-2-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)acetamide ;
l-[l-(2-Cyclopropyl-2-hydroxyethyl)-lH-indol-4-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(7-Bromo-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-mdazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid;
1 -Methyl-3-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methylamide; l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-cyanoethyl)amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)methylamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-7-nitro-lH-indol-3- yl)ethanol;
l-(7-Amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid carbamoylmethylamide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid cyanomethylamide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
N-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluoroplienyl)-lH-indazol-5-yl]-l-hydroxyethyl}- lH-indol-7-yl)methanesulfonamide;
3-(3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)propane- 1 ,2-diol;
1 -Benzyl-3 - {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -hydroxy ethyl} - 1 H- indole-7-carboxylic acid methyl ester;
2-(3-{2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}indol-l - yl)acetamide; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol- 3-yl]ethanol;
N-Methyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Cyanomethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Carbamoylmethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
l-Morpholin-4-yl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydr oxyethyl } indo 1- 1 -y l)ethanone ;
1 -Allyl-3-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
1 -( 1 -Allyl- lH-imidazol-4-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yljethanol;
3-(4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}imidazol- 1 -yl)propane- 1 ,2-diol;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
l-(2,3-Dihydroxypropyl)-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}-lH-indole-7-carboxylic acid amide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-(l-^-tolyl-lH-indazol-5-yl)ethanol;
3-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-/'-tolyl-lH-indazol-5-yl)ethyl]indol-l-yl}propane- 1,2-diol; 2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- 1 H-indol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -phenyl- 1 H-indol-5-yl)ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol;
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[I -(2-fluorophenyl)- lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -(I -p-tolyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-methoxyphenyl)-lH-indazol-5-yl]-l-phenylethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-naphthalen-l-yl-l-(l-o-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-(l-o-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(2-fluorophenyl)-lH-indazol-5- yl]ethanol; 2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(4-methoxyphenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro-l-(4-fluoro-3-hydroxymethylphenyl)-l-(l-phenyl-lH-indazol-5- yl)ethanol;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methoxy-4-methyl-lH- indol-3 -yl)ethanol ;
1 -(4-Chloro- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(6-methoxy- 1 H-indol-3- yl)ethanol;
l-(2,5-Dimethyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methoxy-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-3-yl)ethanol;
l-(6-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
l-(7-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol; l-(5-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(2-methyl-lH-indol-3- yl)ethanol;
l-(6-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-mdazol-5- yl]ethanol;
1 -(5-Chloro- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5- yljethanol;
l-(4-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -(4-fluoro- lH-indol-3-yl)- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yljethanol;
2,2,2-Trifluoro-l-(6-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(5-methoxy-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-(7-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methyl-lH-indol-3- yl)ethanol; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methyl-lH-indol-3- yl)ethanol;
3-{2,2,2-Trifluoro-l-[l-(4-fluoroρhenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole-5- carbonitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-3- yl)ethanol;
l-(6-Bromo-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-6-carbonitrile;
2,2,2-Trifluoro-l -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(I -methyl-ό-pyridin-S-yl- IH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-4-yl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-l H-indazol-5-yl]-l -(I -methyl-6-moφholin-4-yl- lH-indol-3-yl)ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-6-carboxylic acid methyl ester;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-furan-2-yl-l-methyl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrimidin-5-yl- lH-indol-3-yl)ethanol; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-{6-[(2- methoxyethyl)methylamino]- 1 -methyl- 1 H-indol-3 -yl } ethanol ;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[6-(2-methoxyethylamino)-l- methyl-lH-indol-3-yl]ethanol;
l-{6-[(2-Dimethylaminoethyl)methylamino]-l-methyl-lH-indol-3-yl}-2,2,2-trifluoro-l- [l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-5-morpholin-4-yl- lH-indol-3-yl)ethanol;
1 -[6-(2-Dimethylaminoethylamino)- 1 -methyl- 1 H-indol-3 -yl]-2,2,2-trifluoro- 1 -[ 1 -(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
l-[5-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrrolidin-l-yl- 1 H-indol-3 -yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]-l -(I -methyl-5-pyrrolidin- 1 -yl- lH-indol-3-yl)ethanol;
l-[6-Bromo-l-(4-methoxybenzyl)-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
N-Carbamoylmethyl-N-methyl-2- { 3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol- 5-yl)ethyl]indol-l-yl}acetamide;
N-Carbamoylmethyl-2- { 3 -[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5- yl)ethyl] indol- 1 -yl } acetamide;
Ν-(2-Methoxyethyl)-N-methyl-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-p-tolyl-lH-indazol- 5 -yl)ethyl] indol- 1 -yl} acetamide ; N-(2-Methoxyethyl)-2- { 3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -_p-tolyl- lH-indazol-5- yl)ethyl]indol- 1 -yl } acetamide;
N-Cyanomethyl-2- { 3 -[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl-lH-indazol-5- yl)ethyl] indol- 1 -yl} acetamide;
N-Methyl-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-p-tolyl-lH-indazol-5-yl)ethyl]indol-l- yl} acetamide;
2-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-/7-tolyl-lH-indazol-5-yl)ethyl]indol-l- yl} acetamide;
2,2,2-Trifluoro- 1 -[ 1 -(2-hydroxyethyl)- lH-indol-3-yl]- 1 -(I -p-tolyl- 1 H-indazol-5- yl)ethanol;
3- {3-[2,2,2-Trifluoro-l -hydroxy- 1 -(I -p-tolyl- lH-indazol-5-yl)ethyl] indol- 1 -yl}propane- 1,2-diol;
1 , 1 ,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1 , 1 , l-Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
3-(4-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
4-Methyl-7-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-l- benzopyran-2-one;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(3 -trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3 -(2- trifluoromethoxyphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(2-trifluoromethylphenoxy)propan-2-ol; 3-(2-Chloro-3 ,5-difluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5 -yl)propan-2- ol;
3 -(5 -Chloro-2-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3-(4-Bromophenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(indan-5-yloxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2,4,6-trichlorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 -yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 2-yloxy)propan-2-ol;
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(2-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2-Chlorophenoxy)-l ,1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6- trichlorophenoxy)propan-2-ol;
3 -(2-Chloro-5 -methylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol; 3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2- trifluoromethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -ø-tolyloxypropan-2-ol ;
3-(2,4-Dimethylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-61;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trimethylphenoxy)propan-2-ol;
3 -(2,6-Dimethylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yljpropan- 2-ol;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(3-Bromophenoxy)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluorophenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3 -(3 , 5 -Difluorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3-(3-Chlorophenoxy)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(3,5-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-m-tolyloxypropan-2-ol; 3-(3,5-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluorophenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3 -(4-Chlorophenoxy)- 1 ,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- trifluoromethylphenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-/»-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(indan-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(naphthalen- 1 -yloxy)propan-2- ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(naphthalen-2-yloxy)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(quinolin-8-yloxy)propan-2-ol;
3-(2,4-Difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-7-yloxy)propan-2-ol; 3-Methoxy-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid ethyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- phenylaminophenoxy)propan-2-ol;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}phenyl)butyramide;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- trifluoromethylsulfanylphenoxy)propan-2-ol;
5-Acetyl-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid methyl ester;
3-(2-Bromo-5-fluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,4- trifluorophenoxy)propan-2-ol;
3-(2,5-Difluorophenoxy)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3 -(4-Chloro-3 -trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]propan-2-ol;
3-(Acridin-4-yloxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-morpholin-4- ylphenoxy)propan-2-ol;
2-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile; 3-(4-Bromo-2-methylphenoxy)-l , 1 , 1 -trifluoro-2~[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(3-Chloro-4-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(5-Chloro-2-methylphenoxy)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,6- trifluorophenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,5- trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(2,4,6- trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
3 -(2-Chloro-4-methylphenoxy)- 1 , 1 , 1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
3 -(4-Chloro-2-fluorophenoxy)- 1 ,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluoro-2-methylphenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-6-methoxyphenoxy)-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol; 3-(2-Chloro-3,5-difluorophenoxy)-l5l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,5- trifluorophenoxy)propan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxyjbenzonitrile;
3 -(4-Bromo-3 -methylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methoxynaphthalen-2- yloxy)propan-2-ol;
3-(2,6-Dichloro-4-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
4- { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropoxy } indan- 1 - one;
5-Bromo-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy } benzonitrile;
1,1,1 -Trifluoro-3 -(2-fluoro-5-methylphenoxy)-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol;
5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2- trifluoromethoxyphenoxy)propan-2-ol; 1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]-3 -(isoquinolin-7-yloxy)propan-2~ ol;
3 -(3 ,4-Dimethoxyphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(3- trifluoromethoxyphenoxy)propan-2-ol;
3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazo 1-5- yl]propan-2-ol;
6-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropylamino}-3H- isobenzofuran- 1 -one;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropylamino}phenyl)acetamide;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(indan-5-ylamino)propan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(indan-4-ylamino)propan-2-ol;
3-(3-Bromophenylaniino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-o-tolylaminopropan-2-ol;
3-(4-Chlorophenylamino)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- 1 H-indazol-5 -yljpropan- 2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-?M-tolylaminopropan-2-ol;
3 -(4-Chloronaphthalen- 1 -ylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol; 1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]-3 -(6-methoxypyridin-3 - ylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 -ylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2- methoxyphenylamino)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluoroρhenyl)-lH-indazol-5-yl]-3-(3- methoxyphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluoroρhenyl)-lH-indazol-5-yl]-3-(4- methoxyphenylamino)propan-2-ol;
3-(3-Chlorophenylamino)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- IH- indazol-5-y ljpropan- 2-ol;
3-(5-Chloro-2-methylphenylamino)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(2,6-Dimethylphenylamino)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluorophenylamino)-2- [ 1 -(4-fluorophenyl)- lH-indazol-5 -yljpropan- 2-ol;
1,1,1 -Trifluoro-2-[l-(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(4- methylsulfanylphenylamino)propan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen-2-ylamino)propan- 2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methylquinolin-8- ylamino)propan-2-ol; 1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(methylphenylamino)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-[(4- methoxyphenyl)methylamino]propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(4-methylindol- 1 -yl)propan-2- ol;
3-[2-(4-Chlorophenyl)indol- 1 -yl]-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
( 1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - lH-indol- 3-yl)acetonitrile;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -3 -(6-methoxyindol- 1 -yl)propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5-yl] -3 -(5 -methylindol- 1 -yl)propan-2- ol;
3 -(4-Benzyloxyindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan- 2-ol;
3 -(4-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3-(6-Chloroindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methylindol- 1 -yl)propan-2- ol; l-fS^^-Trifluoro^-fl-C^fluorophenyO-lH-indazol-S-y^-l-hydroxypropyU-lH-indole- 4-carboxylic acid methyl ester;
1,1,1 -Trifluoro-3-(6-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 3-carboxylic acid methyl ester;
2,2,2-Trifluoro-l-(l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)ethanone;
1,1,1 -Trifluoro-3 -(4-fluoroindol- 1 -yl)-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
N-[2-(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)ethyl] acetamide ;
3 -(7-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2- ol;
3-(7-Chloroindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
(2-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- 1 H-indol-3 -yl)acetic acid ethyl ester;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 5-carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methyl-5-nitroindol- 1 - yl)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-[2-(4-fluorophenyl)indol-l- yl]propan-2-ol; 3-(4-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3 -(6-Bromoindol- 1 -yl)- 1 ,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3-(3-Diniethylammomethyl-6-methoxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
(5 -Methoxy- 1 - { 3 ,3 ,3 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - lH-indol-3-yl)acetonitrile;
(5-Benzyloxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)acetonitrile;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 6-carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-nitroindol-l -yl)propan-2-ol;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 4-carbonitrile;
3-(5-Benzyloxyindol-l -yl)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 5-carbonitrile;
3 -(3 -Dimethylaminomethyl-5 -methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3 -(5-methoxy-2-methylindol- 1 - yl)propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methylindol-l -yl)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(3-methylindol- 1 -yl)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-methylindol-l -yl)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5-nitroindol- 1 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-phenylindol- 1 -yl)propan-2- ol;
(2-Phenyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- 1 H-indol-3 -yl)acetonitrile ;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-pyrrolo[2,3-c]pyridin- 1 - ylpropan-2-ol;
3-(7-Ethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3-(2,3-Dimethyl-5-nitroindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(6-trifluoromethylindol- 1 - yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(7-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 6-carbonitrile; 3-(2,5-Dimethylindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4~fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
3-(6-Benzyloxyindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-pyrrolo[3,2-έ]pyridin-l - ylpropan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-pyrrolo[3,2-c]pyridin- 1 - ylpropan-2-ol,
or a tautomer, prodrug, solvate, or salt thereof.
6. A compound selected from:
l-Biphenyl-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-CS^-DifluorophenyO^^^-trifluoro-l-Cl-phenyl-lH-indazol-S-yOethanol;
1 -(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-methylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-CS-Chloropheny^^^^-trifluoro-l-Cl-phenyl-lH-indazol-S-y^ethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3,5-Dichlorophenyl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro-l-(3-fluorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methylnaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5- yl)ethanol;
1 -(3 ,4-Dichlorophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-fluorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(2,2-Difluoro- 1 ,3-benzodioxol-4-yl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5- yl)ethanol;
1 -(2,2-Difluoro- 1 ,3-benzodioxol-4-yl)-2,2,2-trifluoro- 1 -(I -phenyl-lH-indazol-5- yl)ethanol;
l-(4-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol;
2,2,2-Trifluoro-l-(l-phenyl-lH-indazol-5-yl)-l-(2,4,5-trimethylphenyl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -(2,4,6-trimethylphenyl)ethanol;
1 -(4-fø?t-Butyl-2,6-dimethylphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol; l-(3,5-Dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methoxy-3 ,5-dimethylphenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methoxyphenyl)- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
l-(3,4-Dimethylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoro-4-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-2-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(2,5-Dimethoxyphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(2-moφholin-4-ylmethylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-Biphenyl-2-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(4-Dimethylaminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -(I -phenyl- lH-indazol-5- yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methylnaphthalen-l -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxynaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-naphthalen-2-yl-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro-l-(lH-indol-4-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol; l,l,l-Trifluoro-3-indol-l-yl-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propyl]-lH-indole-3- carbonitrile;
3-(3 ,4-Dihydro-2H-quinoxalin- 1 -yl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan- 2-ol;
3 -(3 ,4-Dihydro-2H-quinolin- 1 -yl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
l,l,l-Trifluoro-3-(3-fluorophenyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -phenyl-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-phenyl-3-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-phenylsulfanylpropan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluorophenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3-phenoxy-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,5-Difluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3 ,5-Dimethoxyphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1 -Benzo[Z?]thiophen-3 -yl-2,2,2-trifluoro- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- 1 H-indazol-5 -y I)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro- 1 -isoquinolin- 1 -yl- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-naphthalen-l-ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(4-methylnaphthalen-l - yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-4- yl)ethanol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1 - 1 ,3-Benzodioxol-4-yl-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol- 5-yl]ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -(I -phenyl-lH-benzotriazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(6-fluoropyridin-2-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
3-(3 -Chloro-2 -fluorophenyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(4-Chloro-3 -fluorophenyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3-(4-ChloiO-2-fluorophenyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol- 5-yl]ethanol;
l-l,3-Benzodioxol-4-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
232,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-7-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-7- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-5- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(I -methyl- lH-indol-6- yl)ethanol;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indole-l- carboxylic acid tert-butyl ester;
1 -(3-Aminophenyl)-2,2,2-trifluoro- 1 -(I -phenyl-lH-indazol-5-yl)ethanol;
N- { 3 - [2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethyl]phenyl } acetamide ;
1 -Methyl-4-{2,2,2-trifluoro-l -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}-lH- quinolin-2-one;
l-(l-Allyl-lH-indol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
3-(4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)propane-l,2-diol;
3-Hydroxy-4-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indo 1- 1 -yl)butyronitrile; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol- 4-yl]ethanol;
2-(4-{2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]-l -hydroxyethyl} indol- 1 - yl)acetamide;
N-Methyl-2-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)acetamide ;
l-[l-(2-Cyclopropyl-2-hydroxyethyl)-lH-indol-4-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
l-(7-Bromo-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
1 -Methyl-3-{2,2,2-trifluoro-l -[I -(4-fluorophenyl)- 1 H-indazol-5-yl]-l -hydroxyethyl} -IH- indole-7-carboxylic acid methylamide;
1 -Methyl-3 - {2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl } - 1 H- indole-7-carboxylic acid (2-cyanoethyl)amide;
1 -Methyl-3-{2,2,2-trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} - IH- indole-7-carboxylic acid (2-methoxyethyl)amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)methylamide; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-7-nitro-lH-indol-3- yl)ethanol;
l-(7-Amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-mdazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid carbamoylmethylamide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid cyanomethylamide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
N-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}- 1 H-indol-7-yl)methanesulfonamide ;
3-(3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)propane- 1 ,2-diol;
l-Benzyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
2-(3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)acetamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol- 3-yl]ethanol;
N-Methyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Cyanomethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl} indol- 1 -yl)acetamide; N-Carbanioylmethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
l-Morpholin-4-yl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxy ethyl } indol- 1 -yl)ethanone ;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
l-(2,3-Dihydroxypropyl)-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}-lH-indole-7-carboxylic acid amide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-(l-jp-tolyl-lH-indazol-5-yl)ethanol;
3-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-p-tolyl-lH-indazol-5-yl)ethyl]indol-l-yl}propane- 1,2-diol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -phenyl- lH-indol-5-yl)ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
1 -(3-Chlorophenyl)-2,2,2-trifluoro- 1 -(I -pyridin-2-yl- lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -pyridin-2-yl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-[l-(2-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol; 2,2,2-Trifluoro- 1 -[I -(2-fluorophenyl)- lH-indazol-5-yl]- 1 -naphthalen- 1 -ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -[ 1 -(2-fluorophenyl)- lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-_p-tolyl-lH-indazol-5-yl)ethanoI;
2,2,2-Trifluoro-l-[l-(4-methoxyphenyl)-lH-indazol-5-yl]-l-phenylethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-(l-o-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-TrifluoiO-l-(5-fluoro-lH-indol-3-yl)-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(2-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-mdol-3-yl)-l-[l-(4-methoxyphenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro-l-(4-fluoro-3-hydroxymethylphenyl)-l-(l-phenyl-lH-indazol-5- yl)ethanol;
4-[2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methoxy-4-methyl-lH- indol-3-yl)ethanol; l-(4-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methoxy-lH-indol-3- yl)ethanol;
l-(2,5-Dimethyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methoxy-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-3-yl)ethanol;
l-(6-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-(7-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
l-(5-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(2-methyl- lH-indol-3- yl)ethanol;
l-(6-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-(5-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol; l-(4-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -(4-fluoro- lH-indol-3-yl)- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yljethanol;
2,2,2-Trifluoro- l-(6-fluoro- lH-indol-3-yl)-l -[I -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methoxy-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-(7-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methyl-lH-indol-3- yl)ethanol;
3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole-5- carbonitrile;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -(I -methyl- 1 H-indol-3 - yl)ethanol;
l-(6-Bromo-l-raethyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-6-carbonitrile; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-3-yl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-4-yl-lH- indol-3 -yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-morpholin-4-yl- lH-indol-3-yl)ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-6-carboxylic acid methyl ester;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-furan-2-yl-l-methyl-lH- indol-3 -yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrimidin-5-yl- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-{6-[(2- methoxyethyl)methylamino] - 1 -methyl- 1 H-indol-3 -yl } ethanol;
2,2,2-Trifluoro-l-[l-(4-fluoiOphenyl)-lH-indazol-5-yl]-l-[6-(2-methoxyethylamino)-l- methyl- lH-indol-3-yl]ethanol;
1 - { 6- [(2-Dimethylaminoethyl)methylamino] - 1 -methyl- 1 H-indol-3 -yl } -2,2,2-trifluoro- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(I -methyl-5-morpholin-4-yl- lH-indol-3-yl)ethanol;
l-[6-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol; l-[5-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrrolidin-l-yl- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]- 1 -(I -methyl-5-pyrrolidin- 1 -yl- lH-indol-3-yl)ethanol;
l-[6-Bromo-l-(4-methoxybenzyl)-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4-fluorophenyl)- lH-indazol-5-yl]ethanol;
N-Carbamoylmethyl-N-methyl-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-p-tolyl-lH-indazol- 5-yl)ethyl]indol-l-yl}acetamide;
N-Carbamoylmethyl-2- { 3 - [2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- 1 H-indazol-5- yl)ethyl] indol- 1 -yl} acetamide;
N-(2-Methoxyethyl)-N-methyl-2- {3 -[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol- 5-yl)ethyl]indol-l-yl}acetamide;
N-(2-Methoxyethyl)-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-p-tolyl-lH-indazol-5- yl)ethyl] indol- 1 -yl } acetamide;
N-Cyanomethyl-2- { 3 - [2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-to\yl- 1 H-indazol-5 - yl)ethyl] indol- 1 -yl}acetamide;
N-Methyl-2- { 3-[2,2,2-trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethyl]indol- 1 - yl}acetamide;
2- {3-[2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol-5-yl)ethyl] indol- 1 - yl}acetamide;
2,2,2-Trifluoro- 1 -[ 1 -(2-hydroxyethyl)- 1 H-indol-3-yl]- 1 -( 1 -p-tolyl- 1 H-indazol-5- yl)ethanol; 3-{3-[2,2,2-Trifluoro-l-hydroxy-l-(l-/;-tolyl-lH-indazol-5-yl)ethyl]indol-l-yl}propane- 1,2-diol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)-3-(2-trifluoromethylphenoxy)propan-2-ol;
3 -(2-Chloro-3 ,5-difluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
3-(5-Chloro-2-methylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(indan-5-yloxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,4,6-trichlorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol;
3-(3-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2-Bromophenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylphenoxy)propan-2-ol;
3 -(2-Chloro-5-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)-3-(4-trifluoromethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-3 -(naphthalen-2-yloxy)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(2-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; 3-(4-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3 -(4-Chloro-2-fluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluoro-2-methylphenoxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(2,3,4-trifluorophenoxy)propan-2-ol;
3-(2-Chloro-3,5-difluorophenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2- ol;
1,1,1 -Trifluoro-3-(7-methoxynaphthalen-2-yloxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3-(2-Bromo-5-fluorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(2-fluoro-5-trifluoromethylphenoxy)-2-(l-phenyl-lH-indazol-5- yl)propan-2-ol;
3-(4-Bromo-3-methylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1 , 1 ,1 -Trifluoro-3-(2-fluoro-5-methylphenoxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-methylsulfanylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-o-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l-phenyl-l H-indazol-5-yl)-3-m-tolyloxypropan-2-ol; l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-/?-tolyloxypropan-2-ol;
3-(2,6-Dimethylphenoxy)- 1 ,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(naphthalen- 1 -yloxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(isoquinolin-7-yloxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2-trifluoromethoxyphenoxy)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-phenylaminophenoxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluoro-5-trifluoromethylphenoxy)-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol;
l,l,l-Trifluoro-3-(2-methylsulfanylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-trifluoromethylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-y l)propan-2- ol;
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2- ol;
3-Methoxy-4-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propoxy]benzoic acid ethyl ester; 1,1,1 -Trifluoro-3-(4-imidazol- 1 -ylphenoxy)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 -yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 2-yloxy)propan-2-ol;
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(2-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2,4-Dichlorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trichlorophenoxy)propan-2-ol;
3-(2-Chloro-5-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[ l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2- trifluoromethylphenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-c>-tolyloxypropan-2-ol; 3-(2,4-Dimethylphenoxy)-l , 1 , 1 -trifluoro-2-[l-(4-fluorophenyl)- 1 H-indazol-5 -yl]propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trimethylphenoxy)propan-2-ol;
3-(2,6-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(3-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3-(3 -fluorophenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3 -(3 ,5 -Difluorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3-(3-Chlorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
3 -(3 ,5 -Dichlorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-w-tolyloxypropan-2-ol;
3 -(3 ,5 -Dimethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan- 2-61;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-3-(4-fluorophenoxy)-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol; 3 -(4-Chlorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- trifluoromethylphenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-/>-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]-3-(indan-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(naphthalen- 1 -yloxy)propan-2- ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(naphthalen-2-yloxy)propan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(quinolin-5-yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-8-yloxy)propan-2-ol;
3-(2,4-Difluorophenoxy)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5 -yl]-3 -(quinolin-7-yloxy)propan-2-ol;
3-Methoxy-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid ethyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- phenylaminophenoxy)propan-2-ol;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}phenyl)butyramide; 1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- trifluoromethylsulfanylphenoxy)propan-2-ol;
5-Acetyl-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid methyl ester;
3-(2-Bromo-5-fluorophenoxy)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,4- trifluorophenoxy)propan-2-ol;
3-(2,5-Difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
3-(4-Chloro-3-trifluoromethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol- 5-yl]propan-2-ol;
3 -(Acridin-4-yloxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-morpholin-4- ylphenoxy)propan-2-ol;
2-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3 -(4-Bromo-2-methylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
3-(3-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(5-Chloro-2-methylphenoxy)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,6- trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,5- trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6- trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3 -(4-Chloro-2-fluorophenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluoro-2-methylphenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-6-methoxyphenoxy)-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3-(2-Chloro-3,5-difluorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,5- trifluorophenoxy)propan-2-ol ;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile; 3-(4-Bromo-3-methylphenoxy)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3~(6-methoxynaphthalen-2- yloxy)propan-2-ol;
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]ρropan-2-ol;
4- { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -2-hydroxypropoxy } indan- 1 - one;
5-Bromo-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
l,l,l-Trifluoro-3-(2-fluoro-5-methylphenoxy)-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2- trifluoromethoxyphenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(isoquinolin-7-yloxy)propan-2- ol;
3 -(3 ,4-Dimethoxyphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3- trifluoromethoxyphenoxy)propan-2-ol; 3-(2,4-Dichloro-6-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
l,l,l-Trifluoro-3-(2-isopropylphenylsυlfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
3-(4-Ethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
4-Methyl-7-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-l- benzopyran-2-one ;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5 -yl)-3 -(3 -trifluoromethylphenylsulfanyl)propan- 2-ol;
3-(2,3-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4-trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-3-(naphthalen- 1 -ylsulfanyl)-2-( 1 -phenyl- IH- indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(4-thiophen-2-ylpyrimidin-2- ylsulfanyl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(4-phenylpyrimidin-2-ylsulfanyl)propan- 2-ol;
3 - [4-(4-Chlorophenyl)pyrimidin-2-ylsulfanyl] -1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
6-Methyl-2-[3,3,3-trifluoiO-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-4- trifluoromethylnicotinonitrile; l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(5-trifluoromethylpyridin-2- ylsulfanyl)propan-2-ol;
3 -(2-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
1,1,1 -Trifluoro-2-(l-phenyl- lH-indazol-5-yl)-3-(4- trifluoromethoxyphenylsulfanyl)propan-2-ol;
3-(4-Bromo-2-trifluoromethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-methoxyphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(quinolin-2-ylsulfanyl)propan-2-ol;
3-(4-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyrimidin-2-ylsulfanyl)propan-2-ol;
3 -(4,6-Dimethylpyrimidin-2-ylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
3-(3,4-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(pyridin-4-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3 -(3 -methoxyphenylsulfanyl)-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-methoxyphenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; 3-(2,6-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(3-Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,4-Dimethylphenylsulfanyl)- 1 , 1 , l-trifluoro-2-(l-phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(naphthalen-2-ylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(2-fluorophenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(3-fluorophenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(2,5-Dimethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2- ol;
3 -(2,4-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3-(2,5-Dimethylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dimethylphenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3-(2-Ethylphenylsulfanyl)- 1 , 1 , l-trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
2-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]benzoic acid methyl ester;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylpyrimidin-2- ylsulfanyl)propan-2-ol;
3 -(3 ,5 -Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3-(3,5-Bis-trifluoromethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5- yl)propan-2-ol; 3-(2,4-Difluorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-isopropylphenylsulfanyl)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(3 ,5-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2-trifluoromethylphenylsulfanyl)propan- 2-ol;
3 -(3 ,4-Difluorophenylsulfanyl)- 1 ,1,1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
3-(3-Ethoxyphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-fert-Butylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propylsulfanyl]phenyl}acetamide;
3-(4-Bromophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-nitrophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-o-tolylsulfanylpropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-m-tolylsulfanylpropan-2-ol; 1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-£>-tolylsulfanylpropan-2-ol;
3 -(3 -Chloro-4-fluorophenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3-(3,4-Dimethoxyphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3-(5-tert-Butyl-2-methylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2,4,6-trimethylphenylsulfanyl)propan-2- ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)-3 -(3 -trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-3 -(4-methylsulfanylphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan- 2-ol;
3-(2-Chloro-6-methylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol;
3-(2-ferM3utylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylpyridin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(3- trifluoromethoxyphenylsulfanyl)propan-2-ol; l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-methylindol-l-yl)propan-2- ol;
3-[2-(4-Chlorophenyl)indol-l-yl]-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol; (l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol- 3-yl)acetonitrile;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(6-methoxyindol- 1 -yl)propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-methylindol- 1 -yl)propan-2- ol;
3-(4-Benzyloxyindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-(4-Chloroindol- 1 -yl)-l , 1 , l-trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3-(6-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(6-methylindol- 1 -yl)propan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 4-carboxylic acid methyl ester;
1,1,1 -Trifluoro-3-(6-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 3-carboxylic acid methyl ester;
2,2,2-Trifluoro-l-(l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)ethanone; 1,1,1 -Trifluoro-3-(4-fluoroindol- 1 -yl)-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
N-[2-(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)ethyl] acetamide;
3-(7-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3-(7-Chloroindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
(2-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- 1 H-indol-3 -yl)acetic acid ethyl ester;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - lH-indole- 5-carboxylic acid methyl ester;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-methyl-5-nitroindol-l- yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-[2-(4-fluorophenyl)indol-l - yl]propan-2-ol;
3 -(4-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3 -(6-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3-(3 -Dimethylarainomethyl-6-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indol-3-yl)acetonitrile; (5-Benzyloxy- 1 - { 3 ,3 ,3 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-2- hydroxypropyl } - lH-indol-3 -yl)acetonitrile ;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 6-carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(7-nitroindol-l -yl)propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 4-carbonitrile;
3-(5-Benzyloxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 5-carbonitrile;
3-(3-Dimethylaminomethyl-5-methoxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(5-methoxy-2-methylindol- 1 - yl)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(2-methylindol- 1 -yl)propan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-methylindol-l-yl)propan-2- ol;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(7-methylindol-l -yl)propan-2- ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-nitroindol-l-yl)propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-phenylindol- l-yl)propan-2- ol;
(2-Phenyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indol-3-yl)acetonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-pyrrolo[2,3-c]pyridin-l - ylpropan-2-ol;
3-(7-Ethylindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2,3-Dimethyl-5-nitroindol- 1 -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(6-trifluoromethylindol-l - yl)ρropan-2-ol;
1,1,1 -Trifluoro-3-(7-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)-lH~indazol-5-yl]propan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 6-carbonitrile;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-indol-l-ylpropan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-pyiτolo[2,3-έ]pyridin-l - ylpropan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 2-carboxylic acid ethyl ester;
3 -(2,3-Dimethylindol- 1 -yl)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazol-5-yl]propan- 2-ol; l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 3-carbonitrile;
l-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3 -yl)ethanone;
3-(3-Dimethylaminomethylindol-l-yl)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol- 5-yl]propan-2-ol;
3-(3-Dimethylaminomethyl-5-methoxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol- 3-yl)acetic acid ethyl ester;
2-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3-yl)acetamide;
3-(5-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-3-(5-fluoroindol-l -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3-(5-Chloroindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(5 -methoxyindol- 1 -yl)propan- 2-ol;
3-(5,6-Dimethoxyindol-l -yl)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1 ,1 ,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(4-nitroindol- 1 -yl)propan-2-ol; and 5-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indole-2-carboxylic acid ethyl ester,
or a tautomer, prodrug, solvate, or salt thereof.
7. A compound selected from:
l-Biphenyl-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3,4-DifluoiOphenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
l-(3,5-Difluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chloro-5-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-methylphenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-(3-Chlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl-lH-indazol-5-yl)ethanol;
l-(4-Chloro-3-fluorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3 -fluorophenyl)- 1 -(I -phenyl- IH- indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-methylnaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
l-(2,3-Dihydrobenzo[l,4]dioxin-6-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5- yl)ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol; 2,2,2-Trifluoro-l-(4-fluorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-fluoro-4-methylphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
l-Benzo[l,3]dioxol-5-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -(4-Chlorophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(3-methoxyphenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(3-fluoro-4-methylphenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5- yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol ;
1 -(4-Dimethylaminonaphthalen- 1 -yl)-2,2,2-trifluoro- 1 -( 1 -phenyl- IH- indazol-5- yl)ethanol;
2,2,2-Trifluoro- 1 -(2-methoxynaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- 1 H-indazol-5 -yl)- 1 -quinolin-4-ylethanol;
2,2,2-Trifluoro-l-(lH-indol-4-yl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1,1,1 -Trifluoro-3-(3-fluorophenyl)-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-phenyl-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(3 , 5 -Difluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-(l-phenyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(I -phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol; 2,2,2-Trifluoro- 1 -isoquinolin- 1 -yl- 1 -(I -phenyl- lH-indazol-5-yl)ethanol;
l-Benzo[δ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-phenylethanol;
l-(3-Chloro-4-fluorophenyl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]-l -naphthalen- 1 -ylethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5- yljethanol;
2,2J2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(4-methylnaphthalen-l- yl)ethanol;
l-Benzo[έ]thiophen-3-yl-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
1-1 ,3-Benzodioxol-4-yl-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- 1 H-indazol-5 -yl] ethanol;
l-(2,2-Difluoro-l,3-benzodioxol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol- 5-yl]ethanol;
2,2,2-Trifluoro- 1 -(6-fluoropyridin-2-yl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
3-(3-Chloro-2 -fluorophenyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-fluorophenyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-2 -fluorophenyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1 -(2,2-Difluoro- 1 ,3 -benzodioxol-4-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]ethanol; 1-1 ,3-Benzodioxol-4-yl-2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-7-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(I -methyl- lH-indol-7- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-5- yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-6- yl)ethanol;
4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indole-l- carboxylic acid tert-butyl ester;
1 -(3 -Aminophenyl)-2,2,2-trifluoro- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethanol;
N- { 3 - [2,2,2-Trifluoro- 1 -hydroxy- 1 -( 1 -phenyl- 1 H-indazol-5 -yl)ethyl]phenyl } acetamide ;
l-Methyl-4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- quinolin-2-one;
l-(l-Allyl-lH-indol-4-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
3-(4-{2,2,2-Trifluoro-l -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-l -hydroxyethyl} indol- 1 - yl)propane-l,2-diol;
3-Ηydroxy-4-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)butyronitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol- 4-yl]ethanol; 2-(4-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)acetamide;
N-Methyl-2-(4-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl} indol- 1 -yl)acetamide;
l-[l-(2-Cyclopropyl-2-hydroxyethyl)-lH-indol-4-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
1 -(7-Bromo-l -methyl- lH-indol-3-yl)-2,2,2-trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5- yljethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
1 -Methyl-3-{2,2,2-trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methylamide;
1 -Methyl-3-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-7-carboxylic acid (2-cyanoethyl)amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)amide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid (2-methoxyethyl)methylamide;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(I -methyl^-nitro-lH-indol-S- yl)ethanol; l-(7-Amino-l-methyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid carbamoylmethylamide;
l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid cyanomethylamide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
N-(l-Methyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}- 1 H-indol-7-yl)methanesulfonamide ;
3-(3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}indol-l- yl)propane-l,2-diol;
l-Benzyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
2-(3 - {2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl} indol- 1 - yl)acetamide;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[l-(2-hydroxyethyl)-lH-indol- 3-yl]ethanol;
N-Methyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Cyanomethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide;
N-Carbamoylmethyl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl}indol-l-yl)acetamide; l-Morpholin-4-yl-2-(3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l- hydroxyethyl } indol- 1 -yl)ethanone ;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid methyl ester;
l-Allyl-3-{2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-7-carboxylic acid amide;
l-(2,3-Dihydroxypropyl)-3-{2,2,2-trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 - hydroxyethyl}-lH-indole-7-carboxylic acid amide;
l-(l-Allyl-lH-indol-3-yl)-2,2,2-trifluoro-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
3-{3-[2,2,2-Trifluoro- 1 -hydroxy- 1 -(l-^-tolyl-lH-indazol-5-yl)ethyl]indol- 1 -yl}propane- 1,2-diol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -phenyl- lH-indol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -(I -phenyl-lH-indol-5-yl)ethanol;
l-(3,4-Dichlorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
1 -(3-Chlorophenyl)-2,2,2-trifluoro- 1 -(I -pyridin-2-yl- lH-indazol-5-yl)ethanol;
l-(3,4-Difluorophenyl)-2,2,2-trifluoro-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(2-fluorophenyl)-lH-indazol-5-yl]- 1 -phenylethanol;
2,2,2-Trifluoro- 1 - [ 1 -(2-fluorophenyl)- 1 H-indazol-5 -yl] - 1 -naphthalen- 1 -ylethanol ; 2,2,2-Trifluoro-l-(4-fluoronaphthalen-l-yl)-l-[l-(2-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2-Trifluoro-l-phenyl-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-methoxyphenyl)-lH-indazol-5-yl]-l-phenylethanol;
2,2,2-Trifluoro- 1 -phenyl- 1 -( 1 -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -naphthalen- 1 -yl- 1 -( 1 -o-tolyl- lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro- 1 -(4-fluoronaphthalen- 1 -yl)- 1 -( 1 -o-tolyl- 1 H-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-(l-p-tolyl-lH-indazol-5-yl)ethanol;
2,2,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(2-fluorophenyl)-lH-indazol-5- yljethanol;
2,2,2 -Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(4-methoxyphenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -(5-fluoro- lH-indol-3 -yl)- 1 -( 1 -pyridin-2-yl- lH-indazol-5-yl)ethanol;
3-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro- 1 -(4-fluoro-3-hydroxymethylphenyl)- 1 -(I -phenyl-lH-indazol-5- yl)ethanol;
4-[2,2,2-Trifluoro-l-hydroxy-l-(l-phenyl-lH-indazol-5-yl)ethyl]phenol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methoxy-4-methyl-lH- indol-3 -yl)ethanol;
1 -(4-Chloro- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]ethanol; 2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methoxy-lH-indol-3- yl)ethanol;
l-(2,5-Dimethyl-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(7-methoxy-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(lH-indol-3-yl)ethanol;
l-(6-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yljethanol;
l-(7-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-(5-Bromo-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(5-methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(2-methyl- lH-indol-3- yl)ethanol;
1 -(6-Chloro- lH-indol-3-yl)-2,2,2-trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5- yl]ethanol;
l-(5-Chloro-lH-indol-3-yl)-2,2,2-trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
1 -(4-Bromo- lH-indol-3-yl)-2,2,2-trifluoro- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]ethanol; 252,2-Trifluoro-l-(5-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-(4-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -(6-fluoro-lH-indol-3-yl)- 1 -[ 1 ~(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]-l -(5-methoxy- lH-indol-3- yl)ethanol;
2,2,2-Trifluoro-l-(7-fluoro-lH-indol-3-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(6-methyl-lH-indol-3- yl)ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-l -(7-methyl-lH-indol-3- yl)ethanol;
3-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH-indole-5- carbonitrile;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-lH-indol-3- yl)ethanol;
1 -(6-Bromo- 1 -methyl- lH-indol-3-yl)-2,2,2-trifluoro-l -[I -(4-fluorophenyl)-lH-indazol-5- yl]ethanol;
l-Methyl-3-{2,2,2-txifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-hydroxyethyl}-lH- indole-6-carbonitrile; 2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(I -methyl-ό-pyridin-S-yl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyridin-4-yl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -( 1 -methyl-6-morpholin-4-yl- lH-indol-3-yl)ethanol;
1 -Methyl-3-{2,2,2-trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -hydroxyethyl}- IH- indole-6-carboxylic acid methyl ester;
2,2,2-Trifluoro-l -[I -(4-fluorophenyl)- lH-indazol-5-yl]- 1 -(6-furan-2-yl- 1 -methyl-lH- indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrimidin-5-yl- lH-indol-3-yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-{6-[(2- methoxyethyl)methylamino] - 1 -methyl- 1 H-indol-3 -yl } ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-[6-(2-methoxyethylamino)-l- methyl-lH-indol-3-yl]ethanol;
l-{6-[(2-Dimethylammoethyl)methylamino]-l-methyl-lH-indol-3-yl}-2,2,2-trifluoro-l- [l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
2,2,2-Trifluoro- 1 -[I -(4-fluorophenyl)-lH-indazol-5-yl]- 1 -(I -methyl-5-moφholin-4-yl- lH-indol-3-yl)ethanol;
1 -[6-(2-Dimethylaminoethylamino)- 1 -methyl- lH-indol-3-yl]-2,2,2-trifluoro- 1 -[ 1 -(4- fluorophenyl)-lH-indazol-5-yl]ethanol;
l-[5-(2-Dimethylaminoethylamino)-l-methyl-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethanol; 2,252-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-6-pyrrolidin-l-yl- lH-indol-3 -yl)ethanol;
2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-l-(l-methyl-5-pyrrolidin-l-yl- lH-indol-3-yl)ethanol;
l-[6-Bromo-l-(4-methoxybenzyl)-lH-indol-3-yl]-2,2,2-trifluoro-l-[l-(4-fluoroρhenyl)- lH-indazol-5-yl]ethanol;
N-Carbamoylmethyl-N-methyl-2- { 3-[2,2,2-trifluoro~ 1 -hydroxy- 1 -( 1 -p-tolyl- lH-indazol- 5-yl)ethyl]indol-l-yl}acetamide;
N-Carbamoylmethyl-2-{3-[2,2,2-trifluoro-l -hydroxy-1 -(I -/>-tolyl-lH-indazol-5- yl)ethyl]indol-l-yl}acetamide;
Ν-(2-Methoxyethyl)-JV-methyl-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-p-toIyl-lH-indazol- 5-yl)ethyl] indol- 1 -yl } acetamide ;
N-(2-Methoxyethyl)-2-{3-[2,2,2-trifluoro- 1 -hydroxy-1 -(I -p-tolyl- lH-indazol-5- yl)ethyl] indol- 1 -yl } acetamide;
N-Cyanomethyl-2- {3-[2,2,2-trifluoro- 1 -hydroxy- 1 -(I -p-tolyl- lH-indazol-5- yl)ethyl]indol-l-yl}acetamide;
N-Methyl-2-{3-[2,2,2-trifluoro-l-hydroxy-l-(l-p-tolyl-lH-mdazol-5-yl)ethyl]indol-l- yl} acetamide;
2-{3-[2s2,2-Trifluoro-l-hydroxy-l-(l-j3-tolyUH-indazol-5-yl)ethyl]indol-l- yl} acetamide;
2,2,2-Trifluoro-l -[I -(2-hydroxyethyI)-lH-indol-3-ylj- 1 -(I -p-tolyl- lH-indazol-5- yl)ethanol; 3-{3-[2,2,2-Trifluoro-l-hydroxy4-(l-/?-tolyl-lH-indazol-5-yl)ethyl]indol-l-yl}propane- 1,2-diol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2-trifluoromethylphenoxy)propan-2-ol;
3 -(2-Chloro-3 ,5-difluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
3-(5-Chloro-2-methylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3 -(4-Bromophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3-(indan-5-yloxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)-3 -(2,4,6-trichlorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2,4,6-trimethylphenoxy)propan-2-ol;
3-(3-Bromophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(2-Bromophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylphenoxy)propan-2-ol;
3 -(2-Chloro-5 -methylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(4-trifluoromethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-3-(naphthalen-2-yloxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol; 3-(2-Chloro-4-methylphenoxy)-l ,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-2-fluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-fluoro-2-methylphenoxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(2,3,4-trifluorophenoxy)propan-2-ol;
3 -(2-Chloro-3 ,5 -difluorophenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
1,1,1 -Trifluoro-3-(7-methoxynaphthalen-2-yloxy)-2-( 1 -phenyl- IH- indazol-5-yl)propan-2- ol;
3-(2-Bromo-5-fluorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-5-trifluoromethylphenoxy)-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
3-(4-Bromo-3-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1 , 1 , l-Trifluoro-3-(2-fluoro-5-methylphenoxy)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-3-(4-methylsulfanylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1 , 1 , l-Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-o-tolyloxypropan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-»7-tolyloxypropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-p-tolyloxypropan-2-ol; 3-(2,6-Dimethylphenoxy)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(naphthalen- 1 -yloxy)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3-(isoquinolin-7-yloxy)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(2-trifluoromethoxyphenoxy)propan-2-ol;
l,l,l-Trifluoro-3-(4-phenylaminophenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3-Chloro-4-methylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- IH- indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluoro-5-trifluoromethylphenoxy)-2-(l -phenyl- lH-indazol-5- yl)propan-2-ol;
l,l,l-Trifluoro-3-(2-methylsulfanylphenoxy)-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(4-Chloro-3-trifluoromethylphenoxy)-l , 1 , 1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
3-(2,4-Dichloro-6-methylphenoxy)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3-(2,6-Dichloro-4-methylphenoxy)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2- ol;
3-Methoxy-4-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propoxy]benzoic acid ethyl ester;
1,1,1 -Trifluoro-3 -(4-imidazol- 1 -ylphenoxy)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol; 3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5- yl)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 1 -yloxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(5,6,7,8-tetrahydronaphthalen- 2-yloxy)propan-2-ol;
2-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxyjbenzonitrile;
3-(2-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2-Chlorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]propan-2-ol;
3 -(2,4-Dichlorophenoxy)- 1 ,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trichlorophenoxy)propan-2-ol;
3-(2-Chloro-5-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(2,6-Dichlorophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2- trifluoromethylphenoxy)propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -o-tolyloxypropan-2-ol; 3-(2,4-Dimethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,4,6- trimethylphenoxy)propan-2-ol;
3-(2,6-Dimethylphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
3-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(3-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3-(3 -fluorophenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(3,5-Difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
3 -(3 -Chlorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol;
3-(3,5-Dichlorophenoxy)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -rø-tolyloxypropan-2-ol;
3-(3,5-Dimethylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxyjbenzonitrile;
3-(4-Bromophenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluorophenoxy)-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2-ol; 3-(4-Chlorophenoxy)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(4- trifluoromethylphenoxy)propan-2-ol;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-j9-tolyloxypropan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(indan-5-yloxy)propan-2-ol;
l,l,l-Trlfluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(naphthalen-l-yloxy)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(naphthalen-2-yloxy)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-5-yloxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(quinolin-8-yloxy)propan-2-ol;
3-(2,4-Difluorophenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(quinolin-7-yloxy)propan-2-ol;
3-Methoxy-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid ethyl ester;
1 , 1 , l-Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- phenylaminophenoxy)propan-2-ol;
N-(4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}phenyl)butyramide; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(4- trifluoromethylsulfanylphenoxy)propan-2-oI;
5-Acetyl-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzoic acid methyl ester;
3 -(2-Bromo-5-fluorophenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- IH- indazo 1-5- yl]propan-2-ol;
l5l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-mdazol-5-yl]-3-(2J3,4- trifluorophenoxy)propan-2-ol;
3-(2,5-Difluorophenoxy)-l ,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]ρropan-2- ol;
3-(4-Chloro-3-trifluoromethyIphenoxy)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol- 5-yl]propan-2-ol;
3 -(Acridin-4-yloxy)- 1 ,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluoroρhenyl)-lH-indazol-5-yl]-3-(3-morpholin-4- ylphenoxy)ρropan-2-ol;
2-Chloro-4-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
3-(4-Bromo-2-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(3-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
3-(5-Chloro-2-methyIphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2,3,6- trifluorophenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,5- trifluorophenoxy)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,4,6- trifluorophenoxy)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
1 , 1 , 1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-fluoro-5- trifluoromethylphenoxy)propan-2-ol;
3-(2-Chloro-4-methylphenoxy)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
3 -(4-Chloro-2-fluorophenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 - yl]propan-2-ol;
l,l,l-Trifluoro-3-(4-fluoro-2-methylphenoxy)-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3-(2-fluoro-6-methoxyphenoxy)-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol;
3-(2-Chloro-3,5-difluorophenoxy)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2,3,5- trifluorophenoxy)propan-2-ol;
4-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile; 3 -(4-Bromo-3 -methylphenoxy)- 1 ,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(6-methoxynaphthalen-2- yloxy)propan-2-ol;
3-(2,6-Dichloro-4-methylphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazo 1-5- yl]propan-2-ol;
4- { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropoxy } indan- 1 - one;
5-Bromo-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
1,1,1 -Trifluoro-3 -(2-fluoro-5-methylphenoxy)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
5-Chloro-2-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropoxy}benzonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2- trifluoromethoxyphenoxy)propan-2-ol;
1,1,1 -Trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(isoquinolin-7-yloxy)propan-2- ol;
3 -(3 ,4-Dimethoxyphenoxy)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazo 1-5 - yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(3- trifluoromethoxyphenoxy)propan-2-ol; 3-(2,4-Dichloro-6-methylphenoxy)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)-3 -(pyridin-2-ylsulfanyl)propan-2-ol;
3-(4-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l-phenyl- lH-indazol-5-yl)propan-2-ol;
4-Methyl-7-[3,3,3-trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]-l- benzopyran-2-one ;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan- 2-ol;
3-(2,3-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4-trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-3-(naphthalen-l -ylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-thiophen-2-ylpyrimidin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(4-phenylpyrimidin-2-ylsulfanyl)propan- 2-ol;
3 - [4-(4-Chlorophenyl)pyrimidin-2-ylsulfanyl] -1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
6-Methyl-2- [3,3,3 -trifluoro-2-hydroxy-2-( 1 -phenyl- 1 H-indazol-5 -yl)propylsulfanyl] -4- trifluoromethylnicotinonitrile; 1,1,1 -Trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)-3 -(5-trifluoromethylpyridin-2- ylsulfanyl)propan-2-ol;
3-(2-Chloro-4-fluorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan- 2-ol;
1 , 1 , l-Trifluoro-2-(l-ρhenyl- l//-mdazol-5-yl)-3-(4- trifluoromethoxyphenylsulfanyl)propan-2-ol;
3-(4-Bromo-2-trifluoromethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-methoxyphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(quinolin-2-ylsulfanyl)propan-2-ol;
3 -(4-Chlorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-(pyrimidin-2-ylsulfanyl)propan-2-ol;
3-(4,6-Dimethylρyrimidin-2-ylsulfanyI)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5- yl)propan-2-ol;
3-(3,4-Dichiorophenylsulfanyl)-l,l,l'trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(]-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-4-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-methoxyphenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)proρan-2-ol;
1,1,1 -Trifluoro-3-(2-methoxyphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(3-Chlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol; 3-(2,6-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dichlorophenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3 -(3 -Bromophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
3-(3,4-Dimethylphenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(naphthalen-2-ylsulfanyl)-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(2-fluorophenylsulfanyl)-2-(l -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(3-fluorophenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dimethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2- ol;
3-(2,4-Dimethylphenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l-phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,5-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(2,6-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2-Ethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
2-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5-yl)propylsulfanyl]benzoic acid methyl ester;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(4-trifluoromethylpyrimidin-2- ylsulfanyl)propan-2-ol;
3-(3,5-Dimethylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3 -(3 ,5 -B is-trifluoromethylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol; 3-(2,4-Difluorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-isopropylphenylsulfanyl)-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(2,4-Dichlorophenylsulfanyl)-l , 1 , 1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
3-(3,5-Dichlorophenylsulfanyl)-l,l,l-trifluoro-2-(l-phenyl-lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-y l)-3-(2-trifluoromethylphenylsulfanyl)propan- 2-ol;
3 -(3 ,4-Difluorophenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
3-(3-Ethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
3-(4-te/t-Butylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl-lH-indazol-5-yl)propan-2-ol;
N-{4-[3,3,3-Trifluoro-2-hydroxy-2-(l-phenyl-lH-indazol-5- yl)propylsulfanyl]phenyl } acetamide ;
3-(4-Bromophenylsulfanyl)- 1 , 1 , l-trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(4-fluorophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-3-(2-isopropylphenylsulfanyl)-2-( 1 -phenyl- 1 H-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(pyridin-2-ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-3-(4-nitrophenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)-3-o-tolylsulfanylpropan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl-lH-indazol-5-yl)-3-rø-tolylsulfanylpropan-2-ol; 1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-p-tolylsulfanylpropan-2-ol;
3 -(3 -Chloro-4-fluorophenylsulfanyl)- 1 ,1,1 -trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)propan- 2-ol;
3 -(3 ,4-Dimethoxyphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 -yl)propan-2- ol;
3 -(5 -tert-Buty 1-2-methylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- 1 H-indazol-5 - yl)propan-2-ol;
1,1,1 -Trifluoro-2-( 1 -phenyl- lH-indazol-5-yl)-3 -(2,4,6-trimethylphenylsulfanyl)propan-2- ol;
1,1,1 -Trifluoro-2-(l -phenyl- lH-indazol-5-yl)-3-(3-trifluoromethylphenylsulfanyl)propan- 2-ol;
1,1,1 -Trifluoro-3-(4-methylsulfanylphenylsulfanyl)-2-(l -phenyl- lH-indazol-5-yl)propan- 2-ol;
3-(2-Chloro-6-methylphenylsulfanyl)- 1,1,1 -trifluoro-2-( 1 -phenyl- lH-indazo 1-5- yl)propan-2-ol;
3-(2-fert-Butylphenylsulfanyl)- 1,1,1 -trifluoro-2-(l -phenyl- lH-indazol-5-yl)propan-2-ol;
l,l,l-Trifluoro-2-(l-phenyl-lH-indazol-5-yl)-3-(3-trifluoromethylpyridin-2- ylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-(l -phenyl- 1 H-indazol-5 -yl)-3 -(3- trifluoromethoxyphenylsulfanyl)propan-2-ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-3-(4-methylindol- 1 -yl)propan-2- ol; 3-[2-(4-Chlorophenyl)indol-l -yl]-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol- 3-yl)acetonitrile;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(6-methoxyindol- 1 -yl)propan- 2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-methylindol- 1 -yl)propan-2- ol;
3-(4-Benzyloxyindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan- 2-ol;
3-(4-Chloroindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
3 -(6-Chloroindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(6-methylindol-l -yl)propan-2- ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 4-carboxylic acid methyl ester;
1,1,1 -Trifluoro-3-(6-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 3-carboxylic acid methyl ester;
2,2,2-Trifluoro-l-(l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)ethanone ; 1,1,1 -Trifluoro-3-(4-fluoroindol- 1 -yl)-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
N-[2-(5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)ethyl] acetamide;
3-(7-Bromoindol- 1 -yl)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3-(7-Chloroindol-l-yl)-l,l,l-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
(2-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indol-3-yl)acetic acid ethyl ester;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] -2-hydroxypropyl } - 1 H-indole- 5-carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-methyl-5-nitroindol- 1 - yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-[2-(4-fluorophenyl)indol- 1 - yl]propan-2-ol;
3-(4-Bromoindol- 1 -yl)-l , 1 , 1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
3-(6-Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5 -yl]propan-2- ol;
3-(3-Dimethylaminomethyl-6-methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol; (5-Methoxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indol-3-yl)acetonitrile;
(5-Benzyloxy-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2- hydroxypropyl } - 1 H-indol-3 -yl)acetonitrile ;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 6-carboxylic acid methyl ester;
1,1,1 -Trifluoro-2-[l-(4-fluorophenyl)- lH-indazol-5-yl]-3-(7-nitroindol-l -yl)propan-2-ol;
l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 4-carbonitrile;
3-(5-Benzyloxyindol-l -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 5-carbonitrile;
3 -(3 -Dimethylaminomethyl-5 -methoxyindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-methoxy-2-methylindol-l- yl)propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-(2-methylindol-l -yl)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(3-methylindol- 1 -yl)propan-2- ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(7-methylindol-l -yl)propan-2- ol; 1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5-yl]-3-(5-nitroindol- 1 -yl)propan-2-ol;
l,l,l-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-3-(2-phenylindol-l-yl)propan-2- ol;
(2-Phenyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}- lH-indol-3-yl)acetonitrile;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]-3-pyrrolo[2,3-c]pyridin-l - ylpropan-2-ol;
3 -(7-Ethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
3-(2,3 -Dimethyl-5-nitroindol- 1 -yl)- 1 ,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(6-trifluoromethylindol- 1 - yl)propan-2-ol;
1,1,1 -Trifluoro-3 -(7-fluoroindol- 1 -yl)-2-[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan-2- ol;
1 - { 3 ,3 ,3 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 6-carbonitrile;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -indol- 1 -ylpropan-2-ol ;
1,1,1 -Trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -pyrrolo [2,3 -έ]pyridin- 1 - ylpropan-2-ol;
1 - { 3 ,3 ,3 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5 -yl] -2-hydroxypropyl } - 1 H-indole- 2-carboxylic acid ethyl ester;
3-(2,3-Dimethylindol- 1 -yl)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 2-ol; l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indole- 3-carbonitrile;
l-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3 -yl)ethanone;
3 -(3-Dimethylaminomethylindol- 1 -yl)- 1,1,1 -trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol- 5-yl]propan-2-ol;
3-(3-Dimethylaminomethyl-5-methoxyindol-l -yl)- 1,1,1 -trifluoro-2-[l -(4-fluorophenyl)- lH-indazol-5-yl]propan-2-ol;
(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH-indol- 3-yl)acetic acid ethyl ester;
2-(l-{3,3,3-Trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxypropyl}-lH- indol-3 -yl)acetamide;
3 -(5 -Bromoindol- 1 -yl)- 1,1,1 -trifluoro-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
1,1,1 -Trifluoro-3 -(5 -fluoroindol- 1 -yl)-2- [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl]propan-2- ol;
3-(5-Chloroindol-l -yl)- 1,1,1 -trifluoro-2- [1 -(4-fluorophenyl)-lH-indazol-5-yl]propan-2- ol;
1,1,1 -Trifluoro-2-[ 1 -(4-fluorophenyl)- lH-indazol-5 -yl] -3 -(5 -methoxyindol- 1 -yl)propan- 2-ol;
3-(5,6-Dimethoxyindol- 1 -yl)-l , 1 , 1 -trifluoro-2-[l -(4-fluorophenyl)-lH-indazol-5- yl]propan-2-ol;
1,1,1 -Trifluoro-2-[l -(4-fluorophenyl)- 1 H-indazol-5 -yl] -3 -(4-nitroindol- 1 -yl)propan-2-ol; 5-Methyl-l-{3,3,3-trifluoro-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydiOxypropyl}- lH-indole-2-carboxylic acid ethyl ester,
or a tautomer, prodrug, solvate, or salt thereof.
8. A pharmaceutical composition comprising an effective amount of a compound according to one of claims 1 to 7, or a tautomer, prodrug, solvate, or salt thereof, and a pharmaceutically acceptable excipient or carrier.
9. Use of a compound according to one of claims 1 to 7, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition modulating the glucocorticoid receptor function in a patient.
10. Use of a compound according to one of claims 1 to 7, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition to treat a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment.
11. Use of a compound according to one of claims 1 to 10, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition to treat a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma, in a patient in need of such treatment.
12. Use of a compound according to one of claims 1 to 10, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition to treat a disease characterized by inflammatory, allergic, or proliferative processes, in a patient in need of such treatment.
13. The use according to claim 12, wherein the disease is selected from: (i) lung diseases; (ii) rheumatic diseases/autoimmune diseases/joint diseases; (iii) allergic diseases; (iv) vasculitis diseases; (v) dermatological diseases; (vi) renal diseases; (vii) hepatic diseases; (viii) gastrointestinal diseases; (ix) proctological diseases; (x) eye diseases; (xi) diseases of the ear, nose, and throat (ENT) area; (xii) neurological diseases; (xiii) blood diseases; (xiv) tumor diseases; (xv) endocrine diseases; (xvi) organ and tissue transplantations and graft-versus-host diseases; (xvii) severe states of shock; (xviii) substitution therapy; and (xix) pain of inflammatory genesis.
14. Use of a compound according to one of claims 1 to 7, or a tautomer, prodrug, solvate, or salt thereof and a pharmaceutically acceptable glucocorticoid for the preparation of a pharmaceutical composition to treat a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment.
15. A compound of Formula (IB)
Figure imgf000579_0001
wherein:
R1 is aryl, heteroaryl or C3-C7 cycloalkyl each optionally independently substituted with one to three substituent groups selected from C1-C3 alkyl, hydroxy, halogen, oxo, methoxy, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a methyl group, or thiomethyl wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone;
R2 is hydrogen or a halogen;
A and B are each independently CH or N;
C and E are each independently a bond or a -CH2-;
D is -CR4R5-, wherein:
R4 is C1-C8 alkyl, C2-Cg alkenyl, C2-Cg alkynyl, carbocycle, heterocyclyl, aryl, heteroaryl, carbocycle-Q-Cg alkyl, aryl-Ci-C8 alkyl, aryl-Ci-C8 haloalkyl, heterocyclyl-Q-Cs alkyl, heteroaryl-Ci-Cs alkyl, carbocycle-C2-Cs alkenyl, aryl- C2-C8 alkenyl, heterocyclyl-C2-C8 alkenyl, or heteroaryl-C2-C8 alkenyl, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R4 is independently CpC3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C1-C3 alkoxy, aminocarbonyl, CpC3 alkylaminocarbonyl, Cj-C3 dialkylaminocarbonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or CpC3 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein R4 cannot be trifluoromethyl,
R5 is -OH;
is CpC6 alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, NR6R7, OR8, or SR9, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently aryl, heteroaryl, heterocyclyl, CpC5 alkyl, CpC5 alkenyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, CpCs alkanoyloxy, CpCs alkanoyl, aroyl, CpCs alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, Ci-C5 alkylaminocarbonyloxy, CpCs dialkylaminocarbonyloxy, C1-C5 alkanoylamino, CpCs alkoxycarbonylamino, CpC5 alkylsulfonylamino, aminosulfonyl, CpCs alkylaminosulfonyl, CpCs dialkylaminosulfonyl, C1-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, carboxyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a CpCs alkyl, or CpCs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from aryl, heteroaryl, heterocyclyl, acyl, CpC5 alkyl, CpCs alkanoyloxy, CpC5 alkanoyl, CpCs alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, CpCs alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, CpC5 dialkylaminosulfonyl, Cp C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a CpCs alkyl, CpCs cycloalkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or Cj -C3 alkyl, and
R7, R8, and R9 are each independently C1-C5 alkyl, C1-Cs alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl optionally independently substituted with one to three substituent groups,
wherein each substituent group of R7, R8, and R9 is independently heteroaryl, heterocyclyl, C1-C5 alkyl, cycloalkyl, cycloalkenyl, acyl, alkoxycarbonyl, C1-C5 alkanoyloxy, C1-C5 alkanoyl, aroyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C1-C5 alkylaminocarbonyloxy, Ci-C5 dialkylaminocarbonyloxy, Ci-C5 alkanoylamino, Ci-C5 alkoxycarbonylamino, Ci-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R7, R8, and R9 is optionally independently substituted with one to three substituent groups selected from heteroaryl, heterocyclyl, acyl, Ci-C5 alkyl, Ci-C5 alkanoylamino, alkylaminocarbonyl, dialkylaminocarbonyl, Ci-C5 alkylsulfonylamino, aminosulfonyl, Ci-C5 alkylaminosulfonyl, Ci-C5 dialkylaminosulfonyl, Ci-C5 alkyloxy, aryloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, nitro, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a Ci-C5 alkyl, or Ci-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
16. The compound of Formula (IB) according to claim 15, wherein: R1 is aryl or heteroaryl optionally substituted with one to three substituent groups selected from hydroxy, halogen, or oxo;
R2 is hydrogen;
C is a bond;
E is a bond or -CH2-; and
D is -CR4R5-, wherein:
R4 is Ci-C5 alkyl, C2-C5 alkenyl, C3-C6 cycloalkyl, phenyl, C3-C6 cycloalkyl-Ci-C3 alkyl, phenyl-Ci-C3 alkyl, phenyl-Ci-C3 haloalkyl, C3-C6 cycloalkyl-C2-C3 alkenyl, phenyl-C2-C3 alkenyl, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R4 is independently Ci-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, Ci-C3 alkoxy, aminocarbonyl, Ci-C3 alkylaminocarbonyl, Ci-C3 dialkylaminocarbonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, nitro, or Ci-C3 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone, wherein R4 cannot be trifluoromethyl, and
R5 is -OH,
or a tautomer, prodrug, solvate, or salt thereof.
17. The compound of Formula (IB) according to claim 15, wherein:
R1 is a phenyl optionally substituted with one to three halogen groups;
A is N;
B is CH;
D is -CR4R5-, wherein: R4 is C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkyl-methyl-, or benzyl, each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R4 is independently methyl, methoxy, fluoro, chloro, bromo, cyano, trifluoromethyl, or hydroxy, wherein R4 cannot be trifluoromethyl, and
R5 is -OH; and
is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4- dihydro-2H-l,4-benzoxazine, 1,2,3,4-tetrahydroisoquinoline, or N-ethyl-N5- methylbenzene-l,2-diamine, 1,2,3,4-tetrahydroquinoline, NR6R7, OR8, or SR9; each optionally independently substituted with one to three substituent groups,
wherein each substituent group of R3 is independently C1-Cs alkyl, heteroaryl, heterocyclyl, acyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstiruted with a C1-C5 alkyl, C1-Cs alkenyl, carboxyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C1-Cs alkyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein R6 is a hydrogen or a methyl group, and
R7, R8, and R9 are each independently a phenyl, naphthyl, pyridyl, pyrimidyl, quinoline, isoquinoline, or indolyl optionally independently substituted with one to three substituent groups, wherein each substituent group of R7, R8, and R9 is independently heterocyclyl, C1-C5 alkyl, cycloalkyl, acyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1- C5 alkyl, or C1-Cs alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
18. The compound of Formula (IB) according to claim 17, wherein:
R3 is a phenyl, naphthyl, pyridyl, quinoline, isoquinoline, indole, azaindole, benzothiophene, benzofuran, 2,3-dihydro-l,4-benzodioxin, 1,3-benzodioxole, 3,4- dihydro-2H-l,4-benzoxazine, 1,2,3,4-tetrahydroisoquinoline, or N-ethyl-JV- methylbenzene-l,2-diamine, 1,2,3,4-tetrahydroquinoline,
wherein each substituent group of R3 is independently C1-Cs alkyl, acyl, C1-Cs alkyloxy, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-Cs alkyl, C1-C5 alkenyl, carboxyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
wherein each substituent group of R3 is optionally independently substituted with one to three substituents selected from heterocyclyl, C1-C5 alkyl, halogen, hydroxy, oxo, cyano, trifluoromethyl, aminocarbonyl, amino wherein the nitrogen atom is optionally independently mono- or disubstituted with a C1-C5 alkyl, or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
or a tautomer, prodrug, solvate, or salt thereof.
19. A compound selected from:
Cyclopropylphenyl-(l-phenyl-lH-indazol-5-yl)methanol; Cyclopropyl-(3,5-dichlorophenyl)-(l-phenyl-lH-indazol-5-yl)methanol;
(3 -Chloro-4-fluorophenyl)cyclopropyl-( 1 -phenyl- 1 H-indazol-5 -yl)methanol;
Cyclopropylnaphthalen- 1 -yl-( 1 -phenyl- lH-indazol-5-yl)methanol;
Cyclopropyl-(4-fluoronaphthalen-l-yl)-(l-phenyl-lH-indazol-5-yl)methanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-indazol-5-yl]naphthalen-l-ylmethanol;
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)-[l -(4-fluorophenyl)- lH-indazol-5-yl]methanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-indazol-5-yl]quinolin-4-ylmethanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-indazol-5-yl]isoquinolin-l-ylmethanol;
1 -Cyclopropyl- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-2-phenylsulfanylethanol;
1 -Cyclopropyl- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5 -yl] -2-(4- fluorophenylsulfanyl)ethanol;
l-Cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-(naphthalen-l-yloxy)ethanol;
l-Cyclopropyl-2-(3,5-difluorophenoxy)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-Cyclopropyl-2-(3-fluorophenylamino)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]ethanol;
l-Cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-phenylaminoethanol;
l-Cyclopropyl-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-/j-tolylaminoethanol;
2-(4-Chlorophenylamino)- 1 -cyclopropyl- 1 - [ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl] ethanol; l-{2-Cyclopropyl-2-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2-hydroxyethyl}-lH-indole-3- carbonitrile;
1 -Cyclopropyl- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-2-indol-l -ylethanol;
l-{2-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-2-hydroxy-3,3-dimethylbutyl}-lH-indole-3- carbonitrile;
2- [ 1 -(4-Fluorophenyl)- 1 H-indazol-5 -yl] - 1 -indol- 1 -yl-3 ,3 -dimethylbutan-2-ol ;
l-(4-Fluoronaphthalen-l-yl)-l-[l-(4-fluorophenyl)-lH-indazol-5-yl]-2,2-dimethylpropan- l-ol;
l-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-2,2-dimethyl-l-quinolin-4-ylpropan-l-ol;
1 -[I -(4-Fluorophenyl)- lH-indazol-5-yl]-l -isoquinolin-1 -yl-2,2-dimethylpropan- 1 -ol;
Cyclopentylphenyl-( 1 -p-tolyl- 1 H-indazol-5 -yl)methanol;
Cyclopentyl-(3,5-dichlorophenyl)-(l-/7-tolyl-lH-indazol-5-yl)methanol;
(3 -Chloro-4-fluorophenyl)cyclopentyl-( 1 -p-tolyl- 1 H-indazol-5 -yl)methanol;
Cyclohexylphenyl-(l-/?-tolyl-lH-indazol-5-yl)methanol;
Cyclohexyl-(3,5-dichlorophenyl)-(l-p-tolyl-lH-indazol-5-yl)methanol;
(3-Chloro-4-fluorophenyl)cyclohexyl-(l-/>-tolyl-lH-indazol-5-yl)methanol;
2-Cyclohexyl- 1 -phenyl- 1 -(I -pyridin-2-yl- 1 H-indazol-5-yl)ethanol;
2-Cyclohexyl-l-(3,5-dichlorophenyl)-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol;
l-(3-Chloro-4-fluorophenyl)-2-cyclohexyl-l-(l-pyridin-2-yl-lH-indazol-5-yl)ethanol; 1 -(4-Fluoronaphthalen- 1 -yl)- 1 - [ 1 -(4-methoxyphenyl)- 1 H-indazol-5 -yl]propan- 1 -ol;
l-[l-(4-Methoxyphenyl)-lH-indazol-5-yl]-l-quinolin-4-ylpropan-l-ol;
1 -Isoquinolin- 1 -yl- 1 -[ 1 -(4-methoxyphenyl)- lH-indazol-5-yl]propan- 1 -ol;
1 -Benzo [δ]thiophen-3 -yl- 1 - [ 1 -(3 -fluorophenyl)- 1 H-indazol-5 -yl] ethanol;
l-[l-(3-Fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-4-yl)ethanol;
l-[l-(3-Fluorophenyl)-lH-indazol-5-yl]-l-(lH-indol-7-yl)ethanol;
l-(2,3-Dihydro-l,4-benzoxazin-4-yl)-2-[l-(3-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l-(3,4-Dihydro-2H-quinolin-l-yl)-2-[l-(3-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
l-(3,4-Dihydro-2H-quinoxalin-l-yl)-2-[l-(3-fluorophenyl)-lH-indazol-5-yl]propan-2-ol;
1 -(I -Cyclohexyl- lH-indazol-5-yl)-2-methyl- 1 -naphthalen- 1 -ylpropan- 1 -ol;
l-(l-Cyclohexyl-lH-indazol-5-yl)-l-(4-fluoronaphthalen-l-yl)-2-methylpropan-l-ol;
l-(l-Cyclohexyl-lH-indazol-5-yl)-2-methyl-l-quinolin-4-ylpropan-l-ol;
( 1 -Cyclohexyl- 1 H-indazol-5 -yl)isoquinolin- 1 -ylphenylmethanol;
1 -Cyclopropyl-2-phenyl-l -(I -phenyl- lH-indazol-5-yl)ethanol;
l-Cyclopropyl-2-(3,5-dichlorophenyl)-l-(l-phenyl-lH-indazol-5-yl)ethanol;
1 -Cyclopropyl- 1 -( 1 -phenyl- lH-indazol-5-yl)-2-rø-tolylethanol;
l-Cyclopropyl-l-(l-phenyl-lH-indazol-5-yl)-2-/>tolylethanol;
1 -Cyclopropyl-2-(3 -fluorophenyl)- 1 -(I -phenyl- 1 H-indazol-5 -yl)ethanol; 1 -Cyclopropyl- 1 -[ 1 -(4-fluorophenyl)- 1 H-indazol-5-yl]-3 -phenylpropan- 1 -ol;
l-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-2-m-tolylpropan-2-ol;
2-Phenyl- 1 -( 1 -phenyl- lH-indazol-5-yl)propan-2-ol;
l-[l-(4-Fluorophenyl)-lH-indazol-5-yl]-2-methyl-3-phenylpropan-2-ol;
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)-[l -(4-fluorophenyl)- lH-benzotriazol-5- yl]methanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-benzotriazol-5-yl]quinolin-4-ylmethanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-benzotriazol-5-yl]isoquinolin-l-ylmethanol;
Cyclopropylphenyl-( 1 -phenyl- 1 H-benzotriazol-5 -yl)methanol;
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)-[l -(4-fluorophenyl)- lH-benzimidazol-5- yl]methanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-benzimidazol-5-yl]quinolin-4-ylmethanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-benzimidazol-5-yl]isoquinolin-l-ylmethanol;
Cyclopropylphenyl-(l-phenyl-lH-indol-5-yl)methanol;
Cyclopropyl-(4-fluoronaphthalen- 1 -yl)-[l -(4-fluorophenyl)- lH-indol-5-yl]methanol;
Cyclopropyl-[l-(4-fluorophenyl)-lH-indol-5-yl]quinolin-4-ylmethanol;
Cyclopropyl- [ 1 -(4-fluorophenyl)- 1 H-indol-5 -yl] isoquinolin- 1 -ylmethanol;
1 -( 1 -Phenyl- 1 H-indazol-5-yl)- 1 -quinolin-4-ylethanol; 1 -( 1 -Phenyl- 1 H-indazol-5 -yl)- 1 -quinolin-4-ylpropan- 1 -ol;
1 -(4-Fluoronaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)propan- 1 -ol;
1 -(I -Allyl-lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-2-methylpropan-l -ol; and
1 -( 1 -Allyl- lH-indol-3-yl)- 1 -[ 1 -(4-fluorophenyl)- lH-indazol-5-yl]propan- 1 -ol,
or a tautomer, prodrug, solvate, or salt thereof.
20. A compound selected from:
Cyclopropylphenyl-(l-phenyl-lH-indazol-5-yl)methanol;
Cyclopropyl-(3,5-dichlorophenyl)-(l-phenyl-lH-indazol-5-yl)methanol;
1 -Cyclopropyl-2-phenyl- 1 -(I -phenyl-lH-indazol-5-yl)ethanol;
1 -Cyclopropyl-2-(3 ,5 -dichlorophenyl)- 1 -( 1 -phenyl- lH-indazol-5-yl)ethanol;
1 -Cyclopropyl- 1 -(I -phenyl- lH-indazol-5-yl)-2-/?-tolylethanol;
1 -Cyclopropyl- 1 -( 1 -phenyl- lH-indazol-5-yl)-2-m-tolylethanol;
Cyclopropylphenyl-(l-phenyl-lH-benzotriazol-5-yl)methanol;
Cyclopropyl- [ 1 -(4-fluorophenyl)- 1 H-benzotriazol-5 -yl]phenylmethanol;
1 -( 1 -Phenyl- lH-indazol-5-yl)- 1 -quinolin-4-ylethanol;
1 -( 1 -Phenyl- 1 H-indazol-5 -yl)- 1 -quinolin-4-ylpropan- 1 -ol;
1 -(4-Fluoronaphthalen- 1 -yl)- 1 -(I -phenyl- lH-indazol-5-yl)propan- 1 -ol; 1 -(1-AlIyI- lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]-2-methylpropan- l-ol; and
1 -(I -Allyl-lH-indol-3-yl)- 1 -[I -(4-fluorophenyl)- lH-indazol-5-yl]propan- 1 -ol,
or a tautomer, prodrug, solvate, or salt thereof.
21. A pharmaceutical composition comprising an effective amount of a compound according to one of claims 15 to 20, or a tautomer, prodrug, solvate, or salt thereof, and a pharmaceutically acceptable excipient or carrier.
22. Use of a compound according to one of claims 15 to 20, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition modulating the glucocorticoid receptor function in a patient.
23. Use of a compound according to one of claims 15 to 20, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition to treat a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment.
24. Use of a compound according to one of claims 15 to 20, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition to treat a disease-state or condition selected from: type II diabetes, obesity, cardiovascular diseases, hypertension, arteriosclerosis, neurological diseases, adrenal and pituitary tumors, and glaucoma, in a patient in need of such treatment.
25. Use of a compound according to one of claims 15 to 20, or a tautomer, prodrug, solvate, or salt thereof for the preparation of a pharmaceutical composition to treat a disease characterized by inflammatory, allergic, or proliferative processes, in a patient in need of such treatment.
26. The use according to claim 25, wherein the disease is selected from: (i) lung diseases; (ii) rheumatic diseases/autoimmune diseases/joint diseases; (iii) allergic diseases; (iv) vasculitis diseases; (v) dermatological diseases; (vi) renal diseases; (vii) hepatic diseases; (viii) gastrointestinal diseases; (ix) proctological diseases; (x) eye diseases; (xi) diseases of the ear, nose, and throat (ENT) area; (xii) neurological diseases; (xiii) blood diseases; (xiv) tumor diseases; (xv) endocrine diseases; (xvi) organ and tissue transplantations and graft-versus-host diseases; (xvii) severe states of shock; (xviii) substitution therapy; and (xix) pain of inflammatory genesis.
27. Use of a compound according to one of claims 15 to 20, or a tautomer, prodrug, solvate, or salt thereof and a pharmaceutically acceptable glucocorticoid for the preparation of a pharmaceutical composition to treat a disease-state or condition mediated by the glucocorticoid receptor function in a patient in need of such treatment.
PCT/US2006/022651 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof WO2006135826A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CA002610588A CA2610588A1 (en) 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
EP06772813A EP1893588A1 (en) 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
BRPI0611620-5A BRPI0611620A2 (en) 2005-06-10 2006-06-08 glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
CN2006800205382A CN101193869B (en) 2005-06-10 2006-06-08 Glucocortioid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
AU2006257861A AU2006257861A1 (en) 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
MX2007014811A MX2007014811A (en) 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof.
NZ564696A NZ564696A (en) 2005-06-10 2006-06-08 Glucocorticoid, indazole, mimetics, methods of making them, pharmaceutical compositions, and uses thereof
JP2008515997A JP2008543780A (en) 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods for their production, pharmaceutical compositions and their use
IL187976A IL187976A0 (en) 2005-06-10 2007-12-06 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US68941205P 2005-06-10 2005-06-10
US60/689,412 2005-06-10

Publications (1)

Publication Number Publication Date
WO2006135826A1 true WO2006135826A1 (en) 2006-12-21

Family

ID=37057165

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/022651 WO2006135826A1 (en) 2005-06-10 2006-06-08 Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof

Country Status (17)

Country Link
US (1) US7622594B2 (en)
EP (1) EP1893588A1 (en)
JP (1) JP2008543780A (en)
KR (1) KR20080027828A (en)
CN (1) CN101193869B (en)
AR (1) AR058006A1 (en)
AU (1) AU2006257861A1 (en)
BR (1) BRPI0611620A2 (en)
CA (1) CA2610588A1 (en)
IL (1) IL187976A0 (en)
MX (1) MX2007014811A (en)
NZ (1) NZ564696A (en)
PE (1) PE20070112A1 (en)
RU (1) RU2007148225A (en)
TW (1) TW200716573A (en)
WO (1) WO2006135826A1 (en)
ZA (1) ZA200709430B (en)

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008017381A1 (en) 2006-08-08 2008-02-14 Sanofi-Aventis Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use
WO2008057857A1 (en) * 2006-11-01 2008-05-15 Bristol-Myers Squibb Company MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-&kappav;B ACTIVITY AND USE THEREOF
WO2008070507A2 (en) * 2006-12-06 2008-06-12 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
WO2008076048A1 (en) * 2006-12-21 2008-06-26 Astrazeneca Ab Indazolyl ester and amide derivatives for the treatment of glucocorticoid receptor mediated disorders
WO2008079073A1 (en) * 2006-12-22 2008-07-03 Astrazeneca Ab Indazolyl sulphonamide derivatives for the treatment of glucocorticoid receptor mediated disorders
WO2009040288A1 (en) 2007-09-27 2009-04-02 F. Hoffmann-La Roche Ag 1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivatives
WO2009069736A1 (en) * 2007-11-28 2009-06-04 Kyowa Hakko Kirin Co., Ltd. Nitrogenated compound
WO2009142571A1 (en) * 2008-05-20 2009-11-26 Astrazeneca Ab Phenyl and benzodioxinyl substituted indazoles derivatives
WO2010003624A2 (en) 2008-07-09 2010-01-14 Sanofi-Aventis Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof
JP2010518125A (en) * 2007-02-12 2010-05-27 インターミューン・インコーポレーテッド Novel inhibitor of hepatitis C virus replication
WO2010068601A1 (en) 2008-12-08 2010-06-17 Sanofi-Aventis A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof
US7741361B2 (en) 2004-12-27 2010-06-22 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US7795272B2 (en) 2004-03-13 2010-09-14 Boehringer Ingelheim Pharmaceutical, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
WO2010108902A1 (en) * 2009-03-26 2010-09-30 F. Hoffmann-La Roche Ag 1,1,1-trifluoro-2-hydroxypropyl compounds
WO2011023754A1 (en) 2009-08-26 2011-03-03 Sanofi-Aventis Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use
US7932392B2 (en) 2002-03-26 2011-04-26 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US8030340B2 (en) 2006-11-23 2011-10-04 Astrazeneca Ab Indazolyl sulphonamide derivatives useful as glucocorticoid modulators
WO2012120055A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120052A1 (en) 2011-03-08 2012-09-13 Sanofi Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof
WO2012120056A1 (en) 2011-03-08 2012-09-13 Sanofi Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof
WO2012120053A1 (en) 2011-03-08 2012-09-13 Sanofi Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
JP2012521388A (en) * 2009-03-26 2012-09-13 エフ．ホフマン−ラ ロシュ アーゲー 2,3-diaryl- or heteroaryl-substituted 1,1,1-trifluoro-2-hydroxypropyl compounds
WO2012120054A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
US8268859B2 (en) 2008-06-06 2012-09-18 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
EP2567959A1 (en) 2011-09-12 2013-03-13 Sanofi 6-(4-Hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
US8741897B2 (en) 2003-09-24 2014-06-03 Boehringer Ingelheim Pharmaceuticals Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
CN104829591A (en) * 2015-04-27 2015-08-12 南京靖龙药物研发有限公司 Preparation method of deuterated pimozide
WO2017172368A1 (en) 2016-03-31 2017-10-05 Oncternal Therapeutics, Inc. Indoline analogs and uses thereof
US10085986B2 (en) 2011-07-07 2018-10-02 Takeda Pharmaceutical Company Limited Pyrimidinone compounds and their use
RU2677696C1 (en) * 2013-12-09 2019-01-21 Юсб Байофарма Спрл Benzotriazole derivatives as modulators of tnf activity
WO2020179859A1 (en) 2019-03-06 2020-09-10 第一三共株式会社 Pyrrolopyrazole derivative

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR0313923A (en) * 2002-08-29 2005-07-12 Boehringer Ingelheim Pharma 3- (Sulfonamidoethyl) indole derivatives for use as glucocorticoid mimetics in the treatment of inflammatory, allergic and proliferative diseases
JP2012509342A (en) * 2008-11-20 2012-04-19 オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド Substituted pyrrolo [2,3-B] -pyridine and -pyrazine
AR081039A1 (en) 2010-05-14 2012-05-30 Osi Pharmaceuticals Llc QUINASA FUSIONED BICYCLE INHIBITORS
US20130072495A1 (en) 2010-05-14 2013-03-21 OSI Pharmaceuticals, LLC Fused bicyclic kinase inhibitors
US20140088114A1 (en) 2011-05-16 2014-03-27 OSI Pharmaceuticals ,LLC Fused bicyclic kinase inhibitors
WO2017161518A1 (en) * 2016-03-23 2017-09-28 Astrazeneca Ab New physical form
WO2023141595A2 (en) * 2022-01-20 2023-07-27 Terran Biosciences, Inc. Functionalized alkylamines

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000032584A2 (en) * 1998-11-27 2000-06-08 Schering Aktiengesellschaft Nonsteroidal antiinflammatories
WO2003059899A1 (en) * 2002-01-14 2003-07-24 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical formulations containing them and uses thereof
WO2003082787A1 (en) * 2002-03-26 2003-10-09 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
WO2003082280A1 (en) * 2002-03-26 2003-10-09 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
WO2004063163A1 (en) * 2003-01-03 2004-07-29 Boehringer Ingelheim Pharmaceuticals, Inc. 1-propanol and 1-propylamine derivatives and their use as glucocorticoid ligands
WO2005030213A1 (en) * 2003-09-24 2005-04-07 Boehringer Ingelheim Pharmaceuticals, Inc. 1,1,1-trifluoro-4-phenyl-4-methyl-2-(1h-pyrrolo

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200523503A (en) * 2003-09-29 2005-07-16 Sony Corp Backlight, light guiding plate, method for manufacturing diffusion plate and light guiding plate, and liquid crystal display device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000032584A2 (en) * 1998-11-27 2000-06-08 Schering Aktiengesellschaft Nonsteroidal antiinflammatories
WO2003059899A1 (en) * 2002-01-14 2003-07-24 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical formulations containing them and uses thereof
WO2003082787A1 (en) * 2002-03-26 2003-10-09 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
WO2003082280A1 (en) * 2002-03-26 2003-10-09 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
WO2004063163A1 (en) * 2003-01-03 2004-07-29 Boehringer Ingelheim Pharmaceuticals, Inc. 1-propanol and 1-propylamine derivatives and their use as glucocorticoid ligands
WO2005030213A1 (en) * 2003-09-24 2005-04-07 Boehringer Ingelheim Pharmaceuticals, Inc. 1,1,1-trifluoro-4-phenyl-4-methyl-2-(1h-pyrrolo

Cited By (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7932392B2 (en) 2002-03-26 2011-04-26 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US8212040B2 (en) 2002-03-26 2012-07-03 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and thereof
US8741897B2 (en) 2003-09-24 2014-06-03 Boehringer Ingelheim Pharmaceuticals Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
US7795272B2 (en) 2004-03-13 2010-09-14 Boehringer Ingelheim Pharmaceutical, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
US7741361B2 (en) 2004-12-27 2010-06-22 Boehringer Ingelheim Pharmaceuticals, Inc. Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
WO2008017381A1 (en) 2006-08-08 2008-02-14 Sanofi-Aventis Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use
US8198311B2 (en) * 2006-11-01 2012-06-12 Bristol-Myers Squibb Company Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
WO2008057857A1 (en) * 2006-11-01 2008-05-15 Bristol-Myers Squibb Company MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-&kappav;B ACTIVITY AND USE THEREOF
US8030340B2 (en) 2006-11-23 2011-10-04 Astrazeneca Ab Indazolyl sulphonamide derivatives useful as glucocorticoid modulators
WO2008070507A3 (en) * 2006-12-06 2008-09-12 Boehringer Ingelheim Int Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US8658637B2 (en) 2006-12-06 2014-02-25 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
WO2008070507A2 (en) * 2006-12-06 2008-06-12 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
JP2010512331A (en) * 2006-12-06 2010-04-22 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Glucocorticoid mimetics, methods for their production, pharmaceutical compositions, and uses thereof
EA016895B1 (en) * 2006-12-21 2012-08-30 Астразенека Аб Indazolyl ester and amide derivatives for the treatment of glucocorticoid receptor mediated disorders
WO2008076048A1 (en) * 2006-12-21 2008-06-26 Astrazeneca Ab Indazolyl ester and amide derivatives for the treatment of glucocorticoid receptor mediated disorders
US8143290B2 (en) 2006-12-21 2012-03-27 Astrazeneca Ab Chemical compounds 572
JP2012224647A (en) * 2006-12-21 2012-11-15 Astrazeneca Ab Indazolyl ester and amide derivative for treatment of glucocorticoid receptor-mediated disorder
JP2010513478A (en) * 2006-12-21 2010-04-30 アストラゼネカ・アクチエボラーグ Indazolyl esters and amide derivatives for the treatment of glucocorticoid receptor mediated disorders
US7728030B2 (en) 2006-12-21 2010-06-01 Astrazeneca Ab Chemical compounds 572
WO2008079073A1 (en) * 2006-12-22 2008-07-03 Astrazeneca Ab Indazolyl sulphonamide derivatives for the treatment of glucocorticoid receptor mediated disorders
JP2010518125A (en) * 2007-02-12 2010-05-27 インターミューン・インコーポレーテッド Novel inhibitor of hepatitis C virus replication
JP2010540481A (en) * 2007-09-27 2010-12-24 エフ．ホフマン−ラ ロシュ アーゲー 1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivative
TWI426904B (en) * 2007-09-27 2014-02-21 Hoffmann La Roche 1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivatives
RU2481333C2 (en) * 2007-09-27 2013-05-10 Ф.Хоффманн-Ля Рош Аг 1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivatives
WO2009040288A1 (en) 2007-09-27 2009-04-02 F. Hoffmann-La Roche Ag 1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivatives
KR101174982B1 (en) 2007-09-27 2012-08-20 에프. 호프만-라 로슈 아게 1,1,1-trifluoro-2-hydroxy-3-phenylpropane derivatives
US8883786B2 (en) 2007-09-27 2014-11-11 Hoffmann-La Roche Inc. Glucocorticoid receptor antagonists
US8143280B2 (en) 2007-09-27 2012-03-27 Hoffmann-La Roche Inc. Glucocorticoid receptor antagonists
WO2009069736A1 (en) * 2007-11-28 2009-06-04 Kyowa Hakko Kirin Co., Ltd. Nitrogenated compound
JP2014185188A (en) * 2008-05-20 2014-10-02 Astrazeneca Ab Phenyl- and benzodioxynyl-substituted indazole derivative
US8211930B2 (en) 2008-05-20 2012-07-03 Astrazeneca Ab Phenyl and benzodioxinyl substituted indazoles derivatives
WO2009142571A1 (en) * 2008-05-20 2009-11-26 Astrazeneca Ab Phenyl and benzodioxinyl substituted indazoles derivatives
US9738632B2 (en) 2008-05-20 2017-08-22 Astrazeneca Ab Phenyl and benzodioxinyl substituted indazoles derivatives
WO2009142569A1 (en) * 2008-05-20 2009-11-26 Astrazeneca Ab Phenyl or pyridinyl substituted indazoles derivatives
US9512110B2 (en) 2008-05-20 2016-12-06 Astrazeneca Ab Phenyl and benzodioxinyl substituted indazoles derivatives
US8916600B2 (en) 2008-05-20 2014-12-23 Astrazeneca Ab Phenyl and benzodioxinyl substituted indazoles derivatives
JP2011520955A (en) * 2008-05-20 2011-07-21 アストラゼネカ・アクチエボラーグ Phenyl and benzodioxinyl substituted indazole derivatives
EA018629B1 (en) * 2008-05-20 2013-09-30 Астразенека Аб Phenyl and benzodioxinyl substituted indazoles derivatives
CN102099355A (en) * 2008-05-20 2011-06-15 阿斯利康(瑞典)有限公司 Phenyl and benzodioxinyl substituted indazoles derivatives
CN102112449A (en) * 2008-05-20 2011-06-29 阿斯利康(瑞典)有限公司 Phenyl or pyridinyl substituted indazoles derivatives
EA018629B8 (en) * 2008-05-20 2013-12-30 Астразенека Аб Phenyl and benzodioxinyl substituted indazoles derivatives
US8268859B2 (en) 2008-06-06 2012-09-18 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
WO2010003624A2 (en) 2008-07-09 2010-01-14 Sanofi-Aventis Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof
WO2010068601A1 (en) 2008-12-08 2010-06-17 Sanofi-Aventis A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof
JP2012521388A (en) * 2009-03-26 2012-09-13 エフ．ホフマン−ラ ロシュ アーゲー 2,3-diaryl- or heteroaryl-substituted 1,1,1-trifluoro-2-hydroxypropyl compounds
US8450313B2 (en) 2009-03-26 2013-05-28 Hoffmann-La Roche Inc. 2,3-diaryl- or heteroaryl-substituted 1,1,1-trifluoro-2-hydroxypropyl compounds
AU2010227605B2 (en) * 2009-03-26 2013-09-19 F. Hoffmann-La Roche Ag 1,1,1-trifluoro-2-hydroxypropyl compounds
US8268820B2 (en) 2009-03-26 2012-09-18 Hoffmann-La Roche Inc. 2,3-diaryl- or heteroaryl-substituted 1,1,1-trifluoro-2-hydroxypropyl compounds
US8138189B2 (en) 2009-03-26 2012-03-20 Hoffman-La Roche Inc. Substituted benzene compounds as modulators of the glucocorticoid receptor
JP2012521387A (en) * 2009-03-26 2012-09-13 エフ．ホフマン−ラ ロシュ アーゲー 1,1,1-trifluoro-2-hydroxypropyl compound
WO2010108902A1 (en) * 2009-03-26 2010-09-30 F. Hoffmann-La Roche Ag 1,1,1-trifluoro-2-hydroxypropyl compounds
KR101368074B1 (en) 2009-03-26 2014-02-26 에프. 호프만-라 로슈 아게 1,1,1-trifluoro-2-hydroxypropyl compounds
WO2011023754A1 (en) 2009-08-26 2011-03-03 Sanofi-Aventis Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use
WO2012120053A1 (en) 2011-03-08 2012-09-13 Sanofi Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120056A1 (en) 2011-03-08 2012-09-13 Sanofi Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof
WO2012120052A1 (en) 2011-03-08 2012-09-13 Sanofi Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof
WO2012120055A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120054A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
US10085986B2 (en) 2011-07-07 2018-10-02 Takeda Pharmaceutical Company Limited Pyrimidinone compounds and their use
EP2567959A1 (en) 2011-09-12 2013-03-13 Sanofi 6-(4-Hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
RU2677696C1 (en) * 2013-12-09 2019-01-21 Юсб Байофарма Спрл Benzotriazole derivatives as modulators of tnf activity
CN104829591A (en) * 2015-04-27 2015-08-12 南京靖龙药物研发有限公司 Preparation method of deuterated pimozide
CN104829591B (en) * 2015-04-27 2017-05-03 梯尔希（南京）药物研发有限公司 Preparation method of deuterated pimozide
WO2017172368A1 (en) 2016-03-31 2017-10-05 Oncternal Therapeutics, Inc. Indoline analogs and uses thereof
EP3795563A1 (en) 2016-03-31 2021-03-24 Oncternal Therapeutics, Inc. Indoline analogs and uses thereof
WO2020179859A1 (en) 2019-03-06 2020-09-10 第一三共株式会社 Pyrrolopyrazole derivative

Also Published As

Publication number Publication date
NZ564696A (en) 2011-05-27
KR20080027828A (en) 2008-03-28
ZA200709430B (en) 2008-11-26
JP2008543780A (en) 2008-12-04
IL187976A0 (en) 2008-03-20
US7622594B2 (en) 2009-11-24
EP1893588A1 (en) 2008-03-05
TW200716573A (en) 2007-05-01
CN101193869B (en) 2011-03-02
AR058006A1 (en) 2008-01-23
CA2610588A1 (en) 2006-12-21
RU2007148225A (en) 2009-07-20
BRPI0611620A2 (en) 2009-01-13
US20070060633A1 (en) 2007-03-15
MX2007014811A (en) 2008-02-14
AU2006257861A1 (en) 2006-12-21
CN101193869A (en) 2008-06-04
PE20070112A1 (en) 2007-03-08

Similar Documents

Publication Publication Date Title
US7622594B2 (en) Glucocortioid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
EP1539141B1 (en) 3-(sulfonamidoethyl)-indole derivatives for use as glucocorticoid mimetics in the treatment of inflammatory, allergic and proliferative diseases
US8658637B2 (en) Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
EP1490062B1 (en) Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US7635711B2 (en) Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US7795272B2 (en) Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
US20100317863A1 (en) Glucocorticoid Mimetics, Methods of Making Them, Pharmaceutical Compositions and Uses Thereof
US20040010020A1 (en) Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US20040010148A1 (en) Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
US20100063282A1 (en) Glucocorticoid Mimetics, Methods of Making Them, Pharmaceutical Compositions, and Uses Thereof

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200680020538.2

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2006772813

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: MX/a/2007/014811

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2610588

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 9303/DELNP/2007

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 187976

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 12007502780

Country of ref document: PH

ENP Entry into the national phase

Ref document number: 2008515997

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 564696

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 1020087000662

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2006257861

Country of ref document: AU

Ref document number: 2007148225

Country of ref document: RU

ENP Entry into the national phase

Ref document number: 2006257861

Country of ref document: AU

Date of ref document: 20060608

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: PI0611620

Country of ref document: BR