WO2016128908A1

WO2016128908A1 - Bicyclic compounds, compositions and medicinal applications thereof

Info

Publication number: WO2016128908A1
Application number: PCT/IB2016/050698
Authority: WO
Inventors: Nadim SHAIKH; Partha MUKHOPADHYAY; Yogesh Munot; Bheemashankar A. Kulkarni; Kasim Mookhtiar
Original assignee: Advinus Therapeutics Limited
Priority date: 2015-02-12
Filing date: 2016-02-10
Publication date: 2016-08-18

Abstract

The present disclosure relates to a class of substituted bicyclic compounds of formula (I), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, hydrates, N-oxides, co- crystals, pharmaceutically acceptable salts and pharmaceutical compositions containing them. The disclosure also relates to the process of preparation of compounds of Formula (I). (I) These compounds are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of of retinoic acid-related orphan receptor gamma (ROR_Ƴ) such as inflammatory and/or autoimmune disorder, rheumatoid arthritis, psoriasis, psoriatic arthritis, multiple sclerosis, inflammatory bowel disease, allergic diseases, asthma, COPD, cancer, cell proliferation, type 1 diabetes, myasthenia gravis, hematopoetic disfunction, systemic lupus, erythematosus or other disorders.

Description

BICYCLIC COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS

THEREOF

TECHNICAL FIELD

[01] The present disclosure relates to a series of bicyclic compounds, their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates, hydrates, N- oxides, co-crystals and formulations thereof. The disclosure also relates to process of preparation of these bicyclic compounds (I). The compounds of the present disclosure are identified as inhibitors/modulators of retinoic acid-related orphan receptor gamma (RORy). More particularly, the compounds of present disclosure are useful for preventing; treating or ameliorating RORymediated diseases.

BACKGROUND

[02] RORy is a member of nuclear receptor (NR) superfamily of transcription factor. NR superfamily contains 48 members in humans and includes receptors for steroid hormones, thyroid hormone, various lipids, and oxysterols. NRs function as ligand-dependent transcription factors and share a modular domain structure (Mangelsdorf, D. J et al. .Cell 83, 835-83, 1995) comprising N'-terminal AF1 (or A/B) and DNA-binding (DBD) domains, followed by C'-terminal ligand binding (LBD) and AF2 (or F) domain; both sides are joined by a flexible hinge region (D).

[03] Many of the NRs, including ROR family members (RORa, ROR and RORy), do not have validated ligands and are called orphan nuclear receptors. RORy is expressed as two isoforms due to alternative splicing from RORC gene. The shorter transcript called RORyt or RORy2 lacks two exons at 5 -terminal. Unlike widely expressed RORy in several tissues including the thymus, kidney, liver, and mussels, RORyt is expressed exclusively in immature CD4+CD8+ double positive thymocytes and in a population of lymphoid tissue inducers (LTi) of fetal lever. Among mature T cells, RORyt is expressed in IL-17 secreting T cell populations (eg. Thl7, γδΤ cells etc). The highly conserved N'-DBD of RORy(t) recognizing AGGTCA on DNA (RORE) , while C'-terminal LBD contains 12 a-helices of which H3-H5 are important for co activator or co repressor interactions; H12 contains core motif LYKELF of AF2 domain. At resting stage, RORyt is localized in nucleus and upon ligand binding binds to DNA as monomer (Jetten, M., et al.Prog Nucleic acid Res Mol Biol 69, 205-247, 2001) [04] RORyt is the signature transcription factor for differentiation and function of IL-17 producing T Helper (Thl7) cell lineage, a newly discovered subset of T-helper cell population. Thl7 cells are major producer of IL-17A, IL-17F, IL-22, IL-21 proinflammatory cytokines, which have a major role in many of inflammatory and autoimmune diseases but not limited to psoriasis, multiple sclerosis, rheumatoid arthritis,inflammatory bowl diseases, COPD, Colitis, Crohhn's disease and asthma (Lock et al.Nat. Med. 8, 2002, 500-508; Tzartos et al.Am. J. Pathol, 172, 208, 146-155; Koteke et al.J. din. Invest, 103, 1999, 1345-1352; Kirkham et al.Arthritis Rheum, 54, 2006, 1122; Seiderer et al.Inflamm. BowelDis. 14, 208, 437-445; Wong et al.Clin. Exp. Immunol. 125, 2001, 177-183; Agache et al.Respir. Med. 104, 2010, 1131-1137 and references there in Annuzaito et al, Nat. Rev. Immunol. 5, 2001, 325-331). In murine models of these diseases, inhibition of IL-17 function by neutralizing antibodies or generic disruption of IL-17 or 11-17 receptors amelioraties the diseases course or clinical symptoms( Hu et al.Ann. N. Y. Acad Sci. 1217, 2011, 60-67).

[05] There are recent evidences for role of Thl7 in other autoimmune diseases like systemic lupus erythematosus, Behcet's syndrome, scleroderma, transplant rejection and asthma. Thl7 cells cause major inflammatory response by direct as well as indirect methods, like neutrophil infiltration by IL-17, tissue damage, keratinocyte proliferation by IL-22 etc. Hence, small molecule antagonists of RORyt are expected to inhibit production of these proinflammatory cytokines and have broad potential as novel anti-inflammatory compounds Huang, Q., et al.Arthritis Rheumat 56, 2192-2201, 7, 2007; Kimura, A., et al.Internat Immunopharmacol 11, 319-322, 201 l .RORytinhibitors might be useful in diseases where increased levels of TH17 cells and/or elevated levels of IL-17, IL-22 and IL-23 in infectious disease like mucosal leishmaniasis an dmany more (Boaventura et al.Eur. J. Immunol. 40, 2010, 2830-2836; Hashimoto thyroiditis (Figuerovega et al.J. Clin. Endocrinol. Metab. 95,2010, 953-962 and Kawasaki disease (Jie et al.Clin. Exp. Immunol. 162, 131-137, 2010). Mouse model of cancer showed relevance TH17 cells. Evidences suggest that the effector T cell subset is also involved in tumor immunology, thus giving a way to a new target for cancer therapy {Nat. rev. Immuno. 10, 248-256, 2010).The approach of targeting TH-17 cells also validate in clinical studies with several IL-17 antibodies for several autoimmune disorders.

[06] Disrupting of RORyt in mice also attenuates disease progression or severity in animal models of autoimmunity and inflammation including experimental autoimmune encephalomyelitis (EAE), imiquimod induced psoriasis, colitis and allergic airway disease (Ivanov et al.cell, 126, 2006, 1121-1133; Young et al.Immunity, 28, 2008, 29-39; Pantelyushin et al. J. Clin Invest. 122, 2012, 1152-1156; Leppkes et al. Gastroentrology, 136, 2009, 257-267 and Tilley et al J. Immunol. 178, 2007, 3208-3218.

[07] Several patent applications and publications describe the discovery of small molecule

RORyt inhibitors like thiazoles in WO2012027965 and WO 2012/028100; benzoxazepins in WO 2011107248;amide compounds in WO2011 112263; indole and indazole amides in WO2012106995, WO2014026329 and WO2012064744; isooxazole in WO2012147916; sulfonamides and cyclic sulfonamides in WO2014009447 and WO2013092939; quinolines in WO2014062667; pyrimidine in WO2014062938; pyridine in WO2014125426.

[08] No RORyt inhibitor has yet reached the marketing stage. Therefore, there remains a need for discovering novel RORy inhibitors possessing desirable properties such as pharmacokinetic/pharmacodynamic and or physicochemical and/or other drug like profiles to advance into clinics.

[09] Therefore, there is a strong need for novel small molecule RORymodulators that will have potential clinical utility. These compounds will have medical applications in the disease area of inflammation, autoimmune disorder and cell proliferation, rheumatoid arthritis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, Sjogren's Syndrome, multiple sclerosis, inflammatory bowel disease, allergic diseases, infectious diseases affecting immune system, asthma, type 1 diabetes, myasthenia gravis, hematopoetic disfunction, transplant rejection, cancers, COPD and graft-versus-host disease.

WO2013104598 disclose compounds represented by the formula:

Wherein each symbol is as defined in the specification, and useful as phosphodiesterase 5 inhibitors.

WO2010039982 disclose compounds represented by the formula:

Wherein each symbol is as defined in the specification, and useful as CRTH2 modulator.

US20080249135 disclose compounds represented by the formula:

Wherein each symbol is as defined in the specification, and useful in treatment of Dementia.

WO2013169396 disclose compounds a:

Wherein each symbol is as defined in the specification, and useful for TRPV4 activity in the treatment of glaucoma and related disease.

B. P. Fauber et al. Bioorg. Med. Chem. Lett. 25 (2015) 2907-2912 discloses compounds represented by the formula:

Wherein core is as defined in the description, and described as RORy inverse agonist.

[010] The present disclosure provides a series of novel bicyclic compounds characterized as

RORy inhibitors and their potential use in pathogenesis of diseases as medicament for the treatment ofRORy mediated diseases.

SUMMARY

[Oil] The present disclosure provides bicyclic compounds of Formulae (I), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by RORy activity

Formula (I)

Q represents a bicyclic group selected from formula

# represents point of attachment of Y; U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R are independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkoxy, carboxy, hydroxyl, cyano, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl and heterocyclylalkyl, or

R and R taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, alkenyl, alkynyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

T is a monocyclic or a bicyclic ring system which is saturated, unsaturated or partially unsaturated ring system and optionally have additional heteroatoms selected from O, N or S, and said ring is optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR^aR^b)mOR⁶, -(CR^aR^b)mSR⁶, - (CR^aR^b)mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

Y is group selected from -C(O)- , -C(S)-, -0-, -S(0)_p-, -N(R⁷)- and -(CR^aR^b); R^a and R^b are independently selected from the group consisting of hydrogen, -OR , halogen, haloalkyl, perhaloalkyl and alkyl; or

R^a and R^b taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; Z is -C(O)- or -S(0)_p-;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, - NR⁷C(0)R⁸, -OS(0)_pR⁸, -NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, - (CR⁷R⁸)_nS(0)_pNR⁷R⁸, -(CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, - C(R⁷R⁸)_nCO(R⁷) and -S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵ independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; wherein each substituent is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from alkyl, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, cyano, alkoxy, -(CR^aR^b)_nCOOR⁷, -(CR^aR^b)_nNR⁷R⁸, (CR^aR^b)_nC(0)NR⁷R⁸, -S(0)_pR⁷ or -S0₃H.;

R² and R³ are independently selected from halogen, hydroxyl, cyano, Ci^alkyl, d^alkenyl, C2-C₆alkynyl, haloalkyl, perhaloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl;

R⁶ is selected from hydrogen, alkyl, haloalkyl, alkoxy, carboxy, aminocarbonyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; R⁷ and R⁸ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, carboxy, hydroxyl, cyano, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl and heterocyclylalkyl, or

R⁷ and R⁸ taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, alkenyl, alkynyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

p = 0-2;

m = 0-2;

n = 0-4

DETAILED DESCRIPTION

Definitions

[012] In the structural formulae given herein and throughout the present disclosure, the following terms have the indicated meaning, unless specifically stated otherwise.

[013] The term "optionally substituted" as used herein means that the group in question is either unsubstituted or substituted with one or more of the substituents specified. When the group in question is substituted with more than one substituent, the substituent may be same or different.

[014] The term "alkyl" refers to a monoradical branched or unbranched saturated hydrocarbon chain having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, preferably 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, more preferably 1, 2, 3, 4, 5 or 6 carbon atoms. This term is exemplified by groups such as methyl, ethyl, n-propyl, iso- propyl, n-butyl, iso-butyl, t-butyl, n-hexyl, n-decyl, tetradecyl, and the like.

[015] The term "alkylene" refers to a diradical of a branched or unbranched saturated hydrocarbon chain, having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, preferably 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, more preferably 1, 2, 3, 4, 5 or 6 carbon atoms. This term is exemplified by groups such as methylene (-CH₂-), ethylene (-CH₂CH₂-), the propylene isomers (e.g., -CH₂CH₂CH₂- and -CH(CH₃)CH₂-) and the like.

[016] The term "substituted alkyl" or "substituted alkylene" refers to: (1) an alkyl group or alkylene group as defined above, having 1, 2, 3, 4 or 5 substituents, preferably 1, 2 or 3 substituents, selected from the group consisting of alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, heteroarylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, carboxyalkyl, -SO₃H, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(0)₂NR^aR^a, -NR^aS(0)₂R^a and -S(0)_pR^b, where each R^a is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl heteroarylalkyl, heterocyclyl and heterocyclylalkyl; heterocyclyloxy where R^b is hydrogen, alkyl, aryl, heteroaryl or heterocyclyl. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2, or 3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and - S(0)_pR°, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2; or

(2) an alkyl group or alkylene group as defined above that is interrupted by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms independently selected from oxygen, sulphur and NR^d, where R^d is selected from hydrogen, alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocyclyl, carbonylalkyl, carboxyester, carboxyamide and sulfonyl. All substituents may be optionally further substituted by alkyl, alkoxy, halogen, CF₃, amino, substituted amino, cyano, or - S(0)_pR°, in which R° is alkyl, aryl, or heteroaryl and p is 0, 1, or 2; or

(3) an alkyl or alkylene as defined above that has 1, 2, 3, 4 or 5 substituents as defined above, as well as interrupted by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms as defined above.

[017] The term "alkenyl" refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and even more preferably 2, 3, 4, 5 or 6 carbon atoms and having 1, 2, 3, 4, 5 or 6 double bond (vinyl), preferably 1 double bond. Preferred alkenyl groups include ethenyl or vinyl(-CH=CH2), 1- propylene or allyl (-CH₂CH=CH₂), isopropylene (-C(CH₃)=CH₂), bicyclo [2.2. 1] heptene, and the like.

[018] The term "alkenylene" refers to a diradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and even more preferably 2, 3, 4, 5 or 6 carbon atoms and having 1, 3, 4, 5 or 6 double bond (vinyl), preferably 1 double bond.

[019] The term "substituted alkenyl" refers to an alkenyl group as defined above having 1,

2, 3, 4 or 5 substituents, and preferably 1, 2, or 3 substituents, selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, thiocarbonyl, carboxy, carboxyalkyl, SO₃H, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(0)₂NR^aR^a, - NR^aS(0)₂R^a and -S(0)_pR^b where each R^a is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl heteroarylalkyl, heterocyclyl, heterocyclylalkyl and heterocyclyloxy, where R^b is alkyl, aryl, heteroaryl or heterocyclyl and p is 0, 1 or 2. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2, or 3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and -S(0)_pR°, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[020] The term "alkynyl" refers to a monoradical of an unsaturated hydrocarbon, preferably having from 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and even more preferably 2, 3, 4, 5 or 6 carbon atoms and having 1, 2, 3, 4, 5 or 6 sites of acetylene (triple bond) unsaturation, preferably 1 triple bond. Preferred alkynyl groups include ethynyl, (-C≡CH), propargyl (or prop-l-yn-3-yl,-CH₂C≡CH), homopropargyl (or but-l-yn-4-yl, -CH₂CH₂C≡CH) and the like.

[021] The term "alkynylene" refers to a diradical of a branched or an unbranched unsaturated hydrocarbon group preferably having from 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and even more preferably 2, 3, 4, 5 or 6 carbon atoms and having 1, 3, 4, 5 or 6 sites of acetylene (triple bond) unsaturation, preferably 1 triple bond.

[022] The term "substituted alkynyl" refers to an alkynyl group as defined above having 1,

2, 3, 4 or 5 substituents, and preferably 1, 2, or 3 substituents, selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, -SO₃H, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, - S(0)₂NR^aR^a, -NR^aS(0)₂R^a and -S(0)_pR^b, where each R^a is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl heteroarylalkyl, heterocyclyl, heterocyclylalkyl and heterocyclyloxy, where R^b is alkyl, aryl, heteroaryl or heterocyclyl and p is 0, 1 or 2. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2, or 3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and-S(0)_pR^c where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[023] The term "cycloalkyl" refers to unless otherwise mentioned, carbocyclic groups of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings or spirocyclic rings or bridged rings which may be saturated or partially unsaturated. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclooctyl, and the like, or multiple ring structures such as adamantanyl, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, l,3,3-trimethylbicyclo[2.2. l]hept-2-yl,(2,3,3-trimethylbicyclo[2.2. l]hept-2-yl), or carbocyclic groups to which is fused an aryl group, for example indane, and the like.

[024] The term "substituted cycloalkyl" refers to cycloalkyl groups having 1, 2, 3, 4 or 5 substituents, and preferably 1, 2, or 3 substituents, selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -C(0)R and -S(0)_pR^b, where R is hydrogen, hydroxyl, alkoxy, alkyl and cyclocalkyl, heterocyclyloxy where R^b is alkyl, aryl, heteroaryl or heterocyclyl and p is 0, 1 or 2. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2, or 3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and-S(0)_pR^c, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[025] "Halo" or "Halogen", alone or in combination with any other term means halogens such as chloro (CI), fluoro (F), bromo (Br) and iodo (I). [026] "Haloalkyl" refers to a straight chain or branched chain haloalkyl group with 1 to 6 carbon atoms. The alkyl group may be partly or totally halogenated. Representative examples of haloalkyl groups include but are not limited to fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, 2- fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl and the like.

[027] The term "alkoxy" refers to the group R"-0-, where R" is optionally substituted alkyl or optionally substituted cycloalkyl, or optionally substituted alkenyl or optionally substituted alkynyl; or optionally substituted cycloalkenyl, where alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl are as defined herein. Representative examples of alkoxy groups include but are not limited to methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, trifluoromethoxy, and the like.

[028] The term "aminocarbonyl" refers to the group -C(0)NR'R' where each R' is independently hydrogen, alkyl, aryl, heteroaryl, heterocyclyl or both R^' groups are joined to form a heterocyclic group (e. g. morpholino). Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and -S(0)_pR°, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[029] The term "acylamino" refers to the group -NR"C(0)R" where each R" is independently hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and-S(0)_pR°, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[030] The term "acyloxy" refers to the groups -OC(0)-alkyl, -OC(0)-cycloalkyl, -OC(O)- aryl, -OC(0)-heteroaryl, and -OC(0)-heterocyclyl. Unless otherwise constrained by the definition, all substituents may be optionally further substituted by alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, or -S(0)_pR°, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[031] "Alkoxyalkyl" refers to alkyl groups as defined above wherein at least one of the hydrogen atoms of the alkyl group is replaced by an alkoxy group as defined above. Representative examples of alkoxyalkyl groups include but are not limited to methoxymethyl, methoxyethyl, ethoxymethyl and the like. [032] "Aryloxyalkyl" refers to the group -alkyl-O-aryl. Representative examples of aryloxyalkyl include but are not limited to phenoxymethyl, naphthyloxymethyl, phenoxyethyl, naphthyloxyethyl and the like.

[033] "Di alkylamino" refers to an amino group, to which two same or different straight chain or branched chain alkyl groups with 1 to 6 carbon atoms are bound. Representative examples of di alkylamino include but are not limited to dimethylamino, diethylamino, methyl ethylamino, dipropylamino, dibutylamino and the like.

[034] "Cycloalkylalkyl" refers to an alkyl radical as defined above which is substituted by a cycloalkyl radical as defined above. Representative examples of cycloalkylalkyl include but are not limited to cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 1-cyclopentylethyl, 1-cyclohexylethyl, 2-cyclopentylethyl, 2- cyclohexylethyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylbutyl and the like.

[035] "Aminoalkyl" refers to an amino group that is attached to (Ci^alkylene as defined herein. Representative examples of aminoalkyl include but are not limited to aminomethyl, aminoethyl, 1-aminopropyl, 2-aminopropyl, and the like. The amino moiety of aminoalkyl may be substituted once or twice with alkyl to provide alkylaminoalkyl and dialkylaminoalkyl respectively. Representative examples of alkylaminoalkyl include but are not limited to methylaminomethyl, methylaminoethyl, methylaminopropyl, ethylaminoethyl and the like. Representative examples of dialkylaminoalkyl include but are not limited to dimethylaminomethyl, dimethylaminoethyl, dimethylaminopropyl, N-methyl-N- ethylaminoethyl and the like.

[036] The term "aryl" refers to an aromatic carbocyclic group of 6 to 20 carbon atoms having a single ring (e.g. phenyl) or multiple rings (e.g. biphenyl), or multiple condensed (fused) rings (e.g. naphthyl or anthranyl). Preferred aryls include phenyl, naphthyl and the like.

[037] The term "arylene" refers to a diradical of an aryl group as defined above. This term is exemplified by groups such as 1,4-phenylene, 1,3-phenylene, 1,2-phenylene, 1,4'- biphenylene, and the like.

[038] Unless otherwise constrained the aryl or arylene groups may optionally be substituted with 1, 2, 3 4 or 5 substituents, preferably 1, 2 or 3 substituents, selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, carboxy, carboxyalkyl, -SO₃H, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, - S(0)₂NR^aR^a, -NR^aS(0)₂R^a and -S(0)_pR^b where each R^a is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl; where R^b is hydrogen, alkyl, aryl, heterocyclyl or heteroaryl and p is 0, 1 or 2. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2 or 3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and -S(0)_pR° where R° is hydrogen, alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[039] The term "arylalkyl" refers to an aryl group covalently linked to an alkylene group, where aryl and alkylene are defined herein.

[040] "Optionally substituted arylalkyl" refers to an optionally substituted aryl group covalently linked to an optionally substituted alkylene group. Such arylalkyl groups are exemplified by benzyl, phenethyl, naphthylmethyl, and the like.

[041] The term "aryloxy" refers to the group aryl-0- wherein the aryl group is as defined above, and includes optionally substituted aryl groups as also defined above.

[042] The term "arylthio" refers to the group -S-aryl, where aryl is as defined herein including optionally substituted aryl groups as also defined above.

[043] The term "substituted amino" refers to the group -NR^'R^' where each R^' is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, carboxyalkyl, alkoxycarbonyl, aryl, heteroaryl and heterocyclyl. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1, 2 or 3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and -S(0)_pR°, where R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[044] The term "carboxyalkyl" refers to the groups -alkylene-C(0)OH.

[045] The term "alkylcarboxyalkyl" refers to the groups -alkylene-C(0)OR^d where R^d is alkyl, cycloalkyl, where alkyl, cycloalkyl are as defined herein, and may be optionally further substituted by alkyl, halogen, CF₃, amino, substituted amino, cyano, or -S(0)_pR°, in which R° is alkyl, aryl, or heteroaryl and p is 0, 1 or 2.

[046] The term "heteroaryl" refers to an aromatic cyclic group having 1, 2, 3, 4, 5, 6, 7, 8, 9,

10, 11, 12, 13, 14, or 15 carbon atoms and 1, 2, 3 or 4 heteroatoms selected from oxygen, nitrogen and sulphur within at least one ring. Such heteroaryl groups can have a single ring (e.g. pyridyl or furyl) or multiple condensed rings (e.g. indolizinyl, benzothiazolyl, or benzothienyl). Examples of heteroaryls include, but are not limited to, [1,2,4] oxadiazole, [1,3,4] oxadiazole, [1,2,4] thiadiazole, [1,3,4] thiadiazole, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, furan, thiophene, oxazole, thiazole, triazole, triazine and the like.

[047] The term "heteroarylene" refers to a diradical of a heteroaryl group as defined above.

[048] Unless otherwise constrained the heteroaryl or heterarylene groups can be optionally substituted with 1, 2, 3, 4 or 5 substituents, preferably 1, 2 or 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, thiocarbonyl, carboxy, carboxyalkyl, -SO₃H, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, - S(0)₂NR^aR^a, -NR^aS(0)₂R^a and -S(0)_pR^b, where each R^a is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl heteroarylalkyl, heterocyclyl and heterocyclylalkyl; where R^b is hydrogen, alkyl, aryl, heterocyclyl or heteroaryl, and p is 0, 1 or 2. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and-S(0)_nR^c, where R° is alkyl, aryl, or heteroaryl and n is 0,1 or 2.

[049] The term "heteroarylalkyl" refers to a heteroaryl group covalently linked to an alkylene group, where heteroaryl and alkylene are defined herein.

[050] "Optionally substituted heteroarylalkyl" refers to an optionally substituted heteroaryl group covalently linked to an optionally substituted alkylene group. Such heteroarylalkyl groups are exemplified by 3-pyridylmethyl, quinolin-8-ylethyl, 4-methoxythiazol-2-ylpropyl, and the like.

[051] The term "heterocyclyl" refers to a saturated or partially unsaturated group having a single ring or multiple condensed rings or spirocyclic rings, or bridged rings unless otherwise mentioned, having from 1 to 40 carbon atoms and from 1 to 10 hetero atoms, preferably 1, 2, 3 or 4 heteroatoms, selected from nitrogen, sulphur, phosphorus, and/or oxygen within the ring. Heterocyclic groups can have a single ring or multiple condensed rings, and include tetrahydrofuranyl, morpholinyl, piperidinyl, piperazinyl, dihydropyridinyl, tetrahydroquinolinyl and the like. Unless otherwise constrained by the definition for the heterocyclic substituent, such heterocyclic groups can be optionally substituted with 1, 2, 3, 4 or 5, and preferably 1, 2 or 3 substituents, selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, -C(0)R where R is hydrogen, hydroxyl, alkoxy, alkyl and cyclocalkyl, thiocarbonyl, carboxy, carboxyalkyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, and -S(0)_pR^b, where R^b is hydrogen, alkyl, aryl, heterocyclyl or heteroaryl and p is 0, 1 or 2. Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and -S(0)R°, where R° is alkyl, aryl, or heteroaryl and n is 0, 1 or 2.

[052] The term "heterocyclylalkyl" refers to a heterocyclyl group covalently linked to an alkylene group, where heterocyclyl and alkylene are defined herein.

[053] "Optionally substituted heterocyclylalkyl" refers to an optionally substituted heterocyclyl group covalently linked to an optionally substituted alkylene group.

[054] The term "heteroaryloxy" refers to the group heteroaryl-O.

[055] The term "thiol" refers to the group -SH.

[056] The term "substituted alkylthio" refers to the group -S-substituted alkyl.

[057] The term "heteroarylthio" refers to the group -S-heteroaryl wherein the heteroaryl group is as defined above including optionally substituted heteroaryl groups as also defined above.

[058] The term "sulfoxide" refers to a group -S(O).

[059] "Substituted sulfoxide" refers to a group -S(0)R, in which R is substituted alkyl, substituted aryl, or substituted heteroaryl, as defined herein.

[060] The term "sulfone" or "substituted sulfone" refers to a group -S(0)₂R, in which R is alkyl, aryl, or heteroaryl.

[061] The compounds of the present disclosure may have the ability to crystallize in more than one form, a characteristic known as polymorphism, and all such polymorphic forms ("polymorphs") are encompassed within the scope of the disclosure. Polymorphism generally can occur as a response to changes in temperature or pressure or both, and can also result from variations in the crystallization process. Polymorphs can be distinguished by various physical characteristics, and typically the x-ray diffraction patterns, solubility behavior, and melting point of the compound are used to distinguish polymorphs.

[062] The compounds described herein may contain one or more chiral centers and/or double bonds and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), regioisomers, enantiomers or diastereomers. Accordingly, the chemical structures depicted herein encompass all possible enantiomers and stereoisomers of the illustrated or identified compounds including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically pure or diastereomerically pure) and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers using separation techniques or chiral synthesis techniques well known to the person skilled in the art. The compounds may also exist in several tautomeric forms including the enol form, the keto form and mixtures thereof. Accordingly, the chemical structures depicted herein encompass all possible tautomeric forms of the illustrated or identified compounds.

[063] Compounds may exist in unsolvated forms as well as solvated forms, including hydrated forms and as N-oxides. In general, compounds may be hydrated, solvated or N- oxides. Certain compounds may exist in multiple crystalline or amorphous forms. Also contemplated within the scope of the disclosure are congeners, analogs, hydrolysis products, metabolites and precursor or prodrugs of the compound. In general, unless otherwise indicated, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present disclosure.

[064] "Prodrug" refers to a derivative of a drug molecule as, for example, esters, carbonates, carbamates, ureas, amides or phosphates that requires a transformation within the body to release the active drug. Prodrugs are frequently, although not necessarily, pharmacologically inactive until converted to the parent drug. Prodrugs may be obtained by bonding a promoiety (defined herein) typically via a functional group, to a drug.

[065] "Promoiety" refers to a group bonded to a drug, typically to a functional group of the drug, via bond(s) that are cleavable under specified conditions of use. The bond(s) between the drug and promoiety may be cleaved by enzymatic or non-enzymatic means. Under the conditions of use, for example following administration to a patient, the bond(s) between the drug and promoiety may be cleaved to release the parent drug. The cleavage of the promoiety may proceed spontaneously, such as via a hydrolysis reaction, or it may be catalyzed or induced by another agent, such as by an enzyme, by light, by acid, or by a change of or exposure to a physical or environmental parameter, such as a change of temperature, pH, etc. The agent may be endogenous to the conditions of use, such as an enzyme present in the systemic circulation to which the prodrug is administered or the acidic conditions of the stomach or the agent may be supplied exogenously. [066] "Pharmaceutically acceptable salt" embraces salts with a pharmaceutically acceptable acid or base. Pharmaceutically acceptable acids include both inorganic acids, for example hydrochloric, sulphuric, phosphoric, diphosphoric, hydrobromic, hydroiodic and nitric acid and organic acids, for example citric, fumaric, maleic, malic, mandelic, ascorbic, oxalic, succinic, tartaric, benzoic, acetic, methane sulphonic, ethanesulphonic, benzene sulphonic or p-toluenesulphonic acid. Pharmaceutically acceptable bases include alkali metal (e.g. sodium or potassium) and alkali earth metal (e.g. calcium or magnesium) hydroxides and organic bases, for example alkyl amines, arylalkyl amines and heterocyclic amines.

[067] Other preferred salts according to the disclosure are quaternary ammonium compounds wherein an equivalent of an anion (M-) is associated with the positive charge of the N atom. M- may be an anion of various mineral acids such as, for example, chloride, bromide, iodide, sulphate, nitrate, phosphate, or an anion of an organic acid such as, for example, acetate, maleate, fumarate, citrate, oxalate, succinate, tartrate, malate, mandelate, trifluoroacetate, methane sulphonate and p-toluenesulphonate. M- is preferably an anion selected from chloride, bromide, iodide, sulphate, nitrate, acetate, maleate, oxalate, succinate or trifluoroacetate. More preferably M- is chloride, bromide, trifluoroacetate or methane sulphonate .

[068] The present disclosure provides compounds of formula (I), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by RORy activity,

Formula (I)

Q represents a bicyclic group selected from formula

Wherein

** represents point of attachment of T;

# represents point of attachment of Y;

U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

T is a monocyclic or a bicyclic ring system which is saturated, unsaturated or partially unsaturated ring system and optionally have additional heteroatoms selected from O, N or S, and said ring is optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, - (CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

Y is a group selected from -C(O)- , -C(S)-, -0-, -S(0)_p-, -N(R⁷)-, -C(S)- and -(CR^aR^b);

R^a and R^b are independently selected from the group consisting of hydrogen, -OR , halogen, haloalkyl, perhaloalkyl and alkyl; or

R^a and R^b taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; Z is -C(O)- or -S(0)_p-; R , R and R are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, - NR⁷C(0)R⁸, -OS(0)_pR⁸, -NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, - (CR⁷R⁸)_nS(0)_pNR⁷R⁸, -(CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, - C(R⁷R⁸)_nCO(R⁷) and -S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵ independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

wherein each substituent is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from alkyl, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, cyano, alkoxy, -(CR^aR^b)_nCOOR⁷, -(CR^aR^b)_nNR⁷R⁸, (CR^aR^b)_nC(0)NR⁷R⁸, -S(0)_pR⁷ or -S0₃H.;

R² and R³ are independently selected from halogen, hydroxyl, cyano,

C2- Cealkynyl, haloalkyl, perhaloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, or arylalkyl;

R⁶ is selected from hydrogen, alkyl, haloalkyl, alkoxy, carboxy, aminocarbonyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

7 8

R and R are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, carboxy, hydroxyl, cyano, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl and heterocyclylalkyl, or

p = 0-2;

m = 0-2;

n = 0-4

According to another embodiment, the present disclosure relates to compounds of formula (I) or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, wherein, U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

T is a monocyclic or a bicyclic ring system which is saturated, unsaturated or partially unsaturated ring system and optionally have additional heteroatoms selected from O, N or S, and said ring is optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, -(CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

R^a and R^b are independently selected from the group consisting of hydrogen, -OR⁷, halogen, haloalkyl, perhaloalkyl and alkyl; or

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, - NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, - (CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and - S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵ independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; wherein each substituent is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from alkyl, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, cyano, alkoxy, -(CR^aR^b)_nCOOR⁷, -(CR^aR^b)_nNR⁷R⁸, (CR^aR^b)_nC(0)NR⁷R⁸, -S(0)_pR⁷ or -S0₃H.;

R² and R³ are independently selected from halogen, hydroxyl, cyano, Ci^alkyl, haloalkyl, perhaloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, or arylalkyl;

p = 0-2;

m = 0-2;

n = 0-4

According to another embodiment, the present disclosure relates to compounds of formula (I) or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, wherein,

U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; T is cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;

wherein T is unsubstituted or substituted with 1 to 4 substituents independently selected from halogen, alkyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, -(CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

Rl, R4 and R5 are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR7R8, -OR7, -S(0)pR7, -S(0)pNR7R8, -NR7S(0)pR8, -NR7C(0)R8, -OS(0)pR8, - NR7C(0)OR8, -(CR7R8)nC(0)OR7, -(CR7R8)n(CO)NR7R8, -(CR7R8)nS(0)pNR7R8, - (CR7R8)nN(R7)C(0)R7, -(CR7R8)nOR7, -C(R7R8)nNR7R8, -C(R7R8)nCO(R7) and - S(0)pC(R7R8)nC(0)OR7; or when R4 or R5 are more than one, then any 2 R4 or 2 R5 independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

R⁶ is selected from hydrogen, alkyl, haloalkyl, alkoxy, carboxy, aminocarbonyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; R⁷ and R⁸ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, carboxy, hydroxyl, cyano, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl and heterocyclylalkyl, or 7 8

p = 0-2;

m = 0-2;

n = 0-4

U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

T is selected from cyclopropyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, phenyl, tetrahydroiuranyl, pyrrolidinyl, pyridinyl, tetrahydropyridinyl, tetrahydropyranyl, piperazinyl, benzodiaxolyl, tetrahydroquinolinyl, morpholinyl, tetrahydronaphthyridinyl, tetrahydrothienopyridinyl, furanyl, pyrimidinyl, oxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, indolyl, quinolinyl, isoquinolinyl or benzooxazolyl;

wherein T is unsubstituted or substituted with 1 to 4 substituents independently selected from halogen, alkyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, - (CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

Y is a group selected from -C(O)- , -0-, -N(R⁷)-, and -(CR^aR^b); R^a and R^b are independently selected from the group consisting of hydrogen, -OR , halogen, haloalkyl, perhaloalkyl and alkyl; or

R^a and R^b taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; Z is -C(O)- or -S(0)p-;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, - NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, - (CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and - S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

p = 0-2;

m = 0-2; n = 0-4

U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

Y is a group selected from -C(O)- , and -(CR^aR^b);

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, - NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, - (CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and - S(0)pC(R R⁵)nC(0)0R^/; or when R or R are more than one, then any 2 R or 2 R independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

wherein each substituent is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from alkyl, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, cyano, alkoxy, -(CR^aR^b)_nCOOR⁷, -(CR^aR^b)_nNR⁷R⁸, (CR^aR^b)_nC(0)NR⁷R⁸, -S(0)_pR⁷ or -S0₃H;

7 8

p = 0-2;

m = 0-2;

n = 0-4

U is selected from NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R are independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkoxy, carboxy, hydroxyl, cyano, aryl or cycloalkyl, , or R and R taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl or aryl;

T is selected from cyclohexyl, cyclohexenyl, phenyl or pyridinyl;

Y is a group selected from -C(O)- , and -(CR^aR^b);

R^a and R^b taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; Z is -C(O)-;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, - S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, -NR⁷C(0)OR⁸, - (CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, -(CR⁷R⁸)_nN(R⁷)C(0)R⁷, - (CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and -S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵ independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

R⁶ is selected from hydrogen, alkyl, haloalkyl, alkoxy, carboxy, aminocarbonyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; 7 8

p = 0-2;

m = 0-2;

n = 0-4

U is CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R are independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkoxy or hydroxyl;

T is phenyl;

Y is -C(O)-;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, - S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, -NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, - (CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, -(CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, - C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and -S(0)_pC(R⁷R⁸)_nC(0)OR⁷;

p = 0-2;

m = 1;

n = 0-4

[075] According to an embodiment, the present disclosure relates to a process for the preparation of a compound of formula (I), their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs and solvates.

[076] According to another embodiment, the present disclosure provide a process for the preparation of a compound of formula (I), their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs and solvates by following synthetic routes as outlined in the Schemes below.

[077] Scheme 1: Preparation of compounds of formula (la):

Scheme 1 illustrates a general method towards the preparation of compounds of formula la. As exemplified in scheme above, compound of formula A, wherein R⁵, U and G are defined herein above which are available commercially or can be prepared by well known methods in the art, may be converted to compounds of formula B with appropriate halogenating agent such as NBS or liq. Br₂ in acetic acid or liq. Br₂ or NCS, pyridine tribromide or sodium bromite. Reaction of compound B with Lewis acid such as aluminium chloride(AlCl₃), zinc chloride(ZnCl₂), alkyl lithium ("BuLi, ^fBuLi, &cBuLi) and alkyl magnesium bromide or chloride (MeMgBr or MeMgCl, EtMgBr or EtMgCl) mediated acylation, sulfenylation, benzylation reaction, benzoylation, formylation, amination with respective acid chloride, sulfonyl chloride or aryl thiol, aryl halide, benzoyl chloride, pyridine carbonyl chloride, benzaldehyde or anilines transformed to compounds of formula C. Subsequent nucleophilic aromatic substitution or metal mediated N-arylation (Buchwald-Hartwig cross coupling reaction), or metal mediated coupling reaction [palladium acetate Pd(OAc)₂, copper acetate (Cu(OAc)₂), copper bromide (CuBr), nickel chloride (N1CI₂.6H₂O)] led to the formation of the final compound of formula la.

Scheme 2: Preparation of compounds of formula (lb)

Scheme 2 illustrates a general method towards the preparation of compounds of formula lb. As exemplified in scheme above, compound of formula D, wherein R⁵, U and G are defined herein above which are available commercially or can be prepared by well known methods in the art, may be converted to compounds of formula E with appropriate halogenating agent such as NBS or liq. Br₂ in acetic acid or liq. Br₂ or NCS, pyridine tribromide or sodium bromite. Reaction of compound E with base such as cesium carbonate, potassium carbonate, DIPEA, pyridine or Et₃N mediated acylation, sulfenylation, benzylation reaction, benzoylation with respective acid chloride, pyridine carbonyl chloride, sulphonyl chloride or aryl thiol benzyl halide transformed to compounds of formula F. Subsequent palladium mediated Suzuki reaction of compound F led to the formation of the final compound formula of lb.

[079] Wherever desired or necessary, in any of the above mentioned processes, any of the compounds of formula (I) may be converted into a pharmaceutically acceptable salt or vice versa or converting one salt form into another pharmaceutically acceptable salt form.

[080] According to another embodiment the present invention provides co-crystals comprising a compound of formula (I) wherein compounds of formula (I) that contain groups capable of acting as donors and/or acceptors for hydrogen bonds may be capable of forming co-crystals with suitable co-crystal formers. These co-crystals may be prepared from compounds of Formula (I) by known co-crystal forming procedures. Such procedures include grinding, heating, co-subliming, co-melting, or contacting in solution compounds of formula (I) with the co-crystal former under crystallization conditions and isolating co-crystals thereby formed.

[081] According to another embodiment the present invention provides pharmaceutical composition comprising, as an active ingredient, at least one compound of formula (I) or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, together with one or more pharmaceutically acceptable carriers or excipients.

[082] According to another embodiment compositions can be prepared by mixing one or more compounds described herein, or pharmaceutically acceptable salts or tautomers thereof, with pharmaceutically acceptable carriers or the like, to treat or ameliorate a variety of RORy related conditions. The pharmaceutical compositions of the present disclosure can be manufactured by methods well known in the art such as conventional granulating, mixing, dissolving, encapsulating, lyophilizing, emulsifying or levigating processes, among others. The compositions can be in the form of, for example, granules, powders, tablets, capsule syrup, suppositories, injections, emulsions, elixirs, suspensions or solutions. The instant compositions can be formulated for various routes of administration, for example, by oral administration, transmucosal administration, rectal administration, topical administration or subcutaneous administration as well as intrathecal, intravenous, intramuscular, intraperitoneal, intranasal, intraocular or intraventricular injection. The compound or compounds of the instant invention can also be administered in a local rather than a systemic fashion, such as injection as a sustained release formulation.

[083] According to another embodiment compounds of Formula (I) of the invention can be used alone or in combination with one or more additional therapeutically active agent.

[084] In one embodiment, the invention provides methods of treating a RORy mediated disease, disorder or syndrome in a subject comprising administering an effective amount of a compound of formula (I).

[085] In another embodiment, the invention provides methods of treating a RORy mediated disease, disorder or syndrome in a subject comprising administering an effective amount of a compound of formula (I) wherein the disease is an inflammatory or autoimmune disease.

[086] In another embodiment, the invention provide the method of treating a RORy mediated disease, disorder or syndrome in a subject comprising administering an effective amount of a compound of formula (I) wherein the disease, disorder, syndrome or condition is rheumatoid arthritis, psoriasis, systemic lupus erythromatosis, lupus nephritis, scleroderma, chronic obstructive pulmonary disease (COPD), asthma, allergic rhinitis, allergic eczema, multiple sclerosis, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, type I diabetes, inflammatory bowel disease, graft versus host disease, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, uveitis, non-radio graphic spondyloarthropathy, chronic pain, acute pain, inflammatory pain, arthritic pain, neuropathic pain, post-operative pain, surgical pain, visceral pain, dental pain, premenstrual pain, central pain, cancer pain, pain due to burns, migraine or cluster headaches, nerve injury, neuritis, neuralgias, poisoning, ischemic injury, interstitial cystitis, viral, parasitic or bacterial infection, post-traumatic injury, or pain associated with irritable bowel syndrome.

[087] In another embodiment, the invention provide the method of treating a RORy mediated disease, disorder or syndrome in a subject comprising administering an effective amount of a compound of formula (I) wherein the disease, disorder, syndrome or condition is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, cough, pain, inflammatory pain, chronic pain, acute pain, arthritis, osteoarthritis, multiple sclerosis, rheumatoid arthritis, colitis, ulcerative colitis and inflammatory bowel disease.

Examples:

[088] The disclosure is further illustrated by the following examples which in no way should be construed as being further limiting. One skilled in the art will readily appreciate that the specific methods and results described are merely illustrative.

[089] Intermediate l-III: (2,6-dichlorophenyl)-(3-iodo-4,5,6,7-tetrahydroindazol-l- yl methanone

Step I: 3-iodo-4,5,6,7-tetrahydro-lH-indazole

To a stirred mixture of indazole (1.0 g, 8 mmol) in DMF (10 mL), potassium hydroxide (1.3 g, 24 mmol) was added at 0 °C. After stirring for 20 min. at room temperature, reaction mixture was cooled to 0 °C and iodine (2.65 g, 10 mmol) dissolved in DMF (10 mL) was added drop wise to reaction mixture. The reaction mixture was stirred at room temperature for 2 h. After completion, water was added and extracted with EtOAc (3 x 15 mL). Combined organic layer was washed with sodium thiosulfite, saturated brine, dried over NaiSO/_t, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (15% EtOAc in hexane) to provide title compound INT 1- II as a light brown solid (1.9 g, 95%). LCMS: m/z 248.9 (M+l)⁺.

Step II: (2,6-dichlorophenyl)-(3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone

Sodium hydride (0.162 g, 4.05mmol) was added to a stirred mixture of 3-iodo-4,5,6,7- tetrahydro-lH-indazole INT-l-II (0.5 g, 2.03 mmol) in THF at 0 °C. 2,6-dichlorobenzoyl chloride (0.54g, 2.23 mmol) was added to reaction mixture and stirred for 2 h at room tempetaure. After completion of reaction, it was cooled to 0 °C and quenched by the addition of water. The aqueous phase was extracted with EtOAc (3 x 15 mL). Combined organic layer was washed with brine, dried over NaiSO/_t, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (20% EtOAc in hexane) to provide title compound INT I as a white solid (0.65 g, 72%). LCMS: m/z 420.9 (M+l)⁺.

Following intermediates were synthesized from their corresponding starting materials following similar sequence of procedures as for the preparation of Intermediate l-III from

INT-l-II

Intermediate IUPAC name Structure LCMS No (M⁺+l)

1-IV (2-chloro-6-fluoro-phenyl)-(3- 404.9 iodo-4,5,6,7-tetrahydroindazol- l-yl)methanone

1-V (2-chloro-4,6-difluoro-phenyl)- 422

(3-iodo-4,5,6,7- tetrahydroindazol- 1 - yl)methanone ok

1-XII (2,4-dimethyl-3-pyridyl)-(3- 380 iodo-4,5,6,7-tetrahydroindazol- l-yl)methanone

I-XIII (2-chloro-4-methyl-3-pyridyl)- 402

(3-iodo-4,5,6,7- tetrahydroindazol- 1 - yl)methanone

I-XIV (3-iodo-4,5,6,7- 436 tetrahydroindazol- 1 -yl)-[2- methyl-4-(trifluoromethyl)-3- pyridyl] methanone o^k

1-XV (4,6-dichloropyrimidin-5-yl)- 382

(3-iodo-4,5,6,7- tetrahydroindazol- 1 - yl)methanone

Synthesis A-2: 4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid

INT-1 -III A-1 A-2

Step I: Synthesis A-1: methyl 4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3- yljbenzoate Tetrakis(triphenylphosphine) palladium (0.052 g, 0.045 mmol) was added to a degassed solution of (2,6-dichlorophenyl)-(3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone INT-1- III (0.2 g, 0.456 mmol), (2-fluoro-4-met oxycarbonyl-phenyl)boromc acid (0.097 g, 0.5 mmol) and potassium carbonate (0.157 g, 1.14 mmol) in 1 ml of water and dioxane (3 mL) under an inert argon atmosphere .^"The reaction medium was heated at 100 °C for 30 min in microwave. After completion, water was added and extracted with EtOAc (3 x 15 mL). The organic phase was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified on combifalsh system with a gradient of 10 to 30% ethyl acetate -hexanes to obtain the desired product A-l(0.050 g, 25%). LCMS: m/z 443.0 (M+l)⁺. ¾ NMR (DMSO-£¾, 400 MHz) δ 1.32 (t, J = 6.8 Hz, 3H), 1.77-1.80 (m, 2H), 1.86-1.89 (m, 2H), 2.71 (t, J = 5.2 Hz, 2H), 3.12 (t, J = 5.6 Hz, 2H), 4.32 (q, J = 6.8 Hz, 2H), 7.33 (bs, 1H), 7.58-7.66 (m, 2H), 7.70 (d, J= 8.4 Hz, 2H), 8.0 (d, J= 8.4 Hz, 2H)

Step II: Synthesis A-2: 4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid

A solution of methyl 4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate A-l (0.060 g, 0.135 mmol) in a mixture of THF: EtOH: H₂0 (2:2: 1, 5 mL) was added LiOH.H₂0 (0.011 g, 0.269 mmol) and the mixture was stirred for 12 h at room temperature. After completion, the solvent was removed under reduced pressure. The crude product was dissolved in the water and acidified with IN HC1 solution up to pH = 3 and extracted with EtOAc (3 x 15 mL). The organic phase was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified on combifalsh system with a gradient of 10 to 30% ethyl acetate-hexanes to obtain the desired product A-2 (0.35 g, 30%). LCMS: m/z 415.0 (M+l)⁺. ^!H NMR (DMSO-t^, 400 MHz) δ 1.77-1.79 (m, 2H), 1.86-1.89 (m, 2H), 2.73 (bs, 2H), 3.13 (t, J= 6 Hz, 2H), 7.59-7.62 (m, 1H), 7.64 (s, 1H), 7.66-7.70 (m, 3H), 7.99 (d, J= 8.4 Hz, 2H), 13.01 (s, lH).

Following intermediates were synthesized from their corresponding starting materials following similar sequence of procedures as for the preparation of A-2 from INT-1-III No Structure/IUPAC name Characterization INT used

A-3 COOMe LCMS: m/z 410.0 (M+l)⁺. ¾ NMR INT- 1 -III

DMSO-d₆, 400 MHz) δ 1.74 (bs, 2H),

1.86-1.89 (m, 2H), 2.50 (bs, 2H), 3.13

(bs, 2H), 3.19 (s, 3H), 7.54-7.59 (m,

2H), 7.61-7.64 (m, 2H), 7.80 (d, J =

10.2 Hz, 1H), 7.85 (d, J= 8.4 Hz, 1H)

CI

4-[ 1 -(2,6-dichlorobenzoyl)- 4,5,6,7-tetrahydroindazol- 3-yl]benzoic acid

A-4 COOH LCMS: m/z 433.0 (M+l)⁺. ¾ NMR INT- 1 -III

(DMSO-^, 400 MHz) δ 1.72-1.76 (m,

2H), 1.86-1.89 (m, 2H), 1.71 (bs, 2H),

3.13 (bs, 2H), 7.51-7.64 (m, 4H), 7.76

(d, J= 10.8 Hz, 1H), 7.82 (d, J= 8.4

Hz, 1H), 13.42 (bs, 1H)

CI

4-[ 1 -(2,6-dichlorobenzoyl)- 4,5,6,7-tetrahydroindazol- 3-yl]-3-fluoro-benzoic acid

A-5 COOMe LCMS: m/z 467.0 (M+l)⁺. ¾ NMR INT- 1 -VII

(DMSO-t/,5, 400 MHz) δ 1.66-1.69 (m,

2H), 1.82-1.85 (m, 2H), 7.45 (bs, 2H),

2.77 (t, J= 6 Hz, 2H), 3.85 (s, 3H),

5.39 (s, 2H), 7.46 (t, J = 8.4 Hz, 1H),

7.63 (t, J= 8.6 Hz, 1H), 7.69 (t, J =

F₃C 10.8 Hz, 1H), 7.75 (d, J= 8 Hz, 1H),

methyl 4-[l-[[2-chloro-6- 7.83 (t, J= 8 Hz, 2H)

(trifluoromethyl)phenyl]me

thyl]-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

A-ll LCMS: m/z 477.0 (M+l)⁺. ¾NMR INT- 1 -III

DMSO-d₆, 400 MHz) δ 1.31 (t, J =

6.8 Hz, 3H), 1.78-1.79 (m, 2H), 1.86-

1.88 (m, 2H), 2.72 (t,J= 5.6 Hz, 2H),

3.31-3.11 (m, 2H), 4.31 (q,J=6.8Hz,

2H), 7.67 (d, J= 8 Hz, 2H), 7.82 (t, J

= 8 Hz, 1H), 7.97 (t, J= 1 Hz, 1H), ethyl 4-[l-[2-chloro-6- 7.99 (d,J=8.8Hz, 3H)

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol-

3-yl]benzoate

A-12 LCMS: m/z 511.1 (M+2)⁺. ¾NMR INT-l-X

(DMSO-t/,5, 400 MHz) δ 1.30 (t, J =

7.6 Hz, 3H), 1.78-1.79 (m, 2H), 1.86-

1.88 (m, 2H), 2.71 (t,J = 6 Hz, 2H),

3.08 (t,J = 6 Hz, 2H), 4.30 ( d, J= 7.6

Hz, 2H), 7.66 (d, J= 8.8 Hz, 2H), 7.98

(d, J= 8 Hz, 2H), 8.05 (t, J= 8.8 Hz, ethyl 4-[l-[2,6- 1H), 8.29 (d,J=8Hz, 2H)

bis(trifluoromethyl)benzoy

11-4,5,6,7- tetrahydroindazol-3 - yl]benzoate

A-13 LCMS: m/z 463.0 (M+l)⁺. ¾NMR INT- 1 -VII

(DMSO-t/,5, 400 MHz) δ 1.30 (t, J =

7.2 Hz, 3H), 1.73-1.75 (m, 2H), 1.82-

1.83 (m, 2H), 2.68 (t,J= 5.6 Hz, 2H),

2.75 (t,J=6Hz, 2H), 4.29 (t, J =5.6

Hz, 2H), 5.40 (s, 2H), 7.61-7.66 (m,

3H), 7.83-7.86 (m, 2H), 7.91 (d,J = ethyl 4-[l-[[2-chloro-6- 8.8 Hz, 2H)

(trifluoromethyl)phenyl]me

thyl]-4,5,6,7-

(trifluoromethyl)phenyl]me

thyl]-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid

A-17 LCMS: m/z 500.0 (M+l)⁺. ¾ NMR INT-l-X

DMSO-d₆, 400 MHz) δ 1.73-1.75 (m,

2H), 1.86-1.88 (m, 2H), 2.47-2.50 (m,

2H), 3.08 (t, J= 6 Hz, 2H), 7.45 (d, J

= 7.6 Hz, 1H), 7.73 (d, J= 10.8 Hz,

1H), 7.79 (d, J= 8 Hz, 1H), 8.02 (t, J

= 8 Hz, 1H), 8.27 (d, J= 8 Hz, 2H),

4-[l-[2,6- 13.40 (s, 1H)

bis(trifluoromethyl)benzoy

11-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-18 COOH LCMS: m/z 467.0 (M+l)⁺. ¾ NMR INT- 1 -IX

(DMSO-t/,5, 400 MHz) δ 1.73 (bs, 2H),

1.87-1.89 (m, 2H), 2.49-2.51 (m, 2H),

' 3.10-3.12 (m, 2H), 7.50 (d, J= 7.6 Hz,

C '^{N c|} 1H), 7.74-7.82 (m, 3H), 7.92 (d, J= 8

Hz, 1H), 7.97 (d, J= 8 Hz, 1H), 13.41

F₃C (s, 1H)

4-[l-[2-chloro-6-

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol-

3-yl]-3-fluoro-benzoic acid

3-yl]-3,5-difluoro-benzoate

A-25 COOH LCMS: m/z 485.0 (M+l)⁺. ¾ NMR INT- 1 -IX

DMSO-d₆, 400 MHz) δ 1.73-1.75 (m,

2H), 1.87-1.88 (m, 2H), 2.35-2.36 (m,

2H), 3.12-3.13 (m, 2H), 7.64 (d, J =

8.0 Hz, 1H), 7.78 (t, J= 8.0 Hz, 1H),

7.90 (t, J= 8.0 Hz, 1H), 7.95 (d, J =

F₃C 7.4 Hz, 1H), 12.84 (s, 1H)

4-[l-[2-chloro-6-

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol-

3-yl]-3,5-difluoro-benzoic

acid

A-26 COOMe LCMS: m/z 493.0 (M+l)⁺. ¾ NMR INT- 1 -IX

(DMSO-t^, 400 MHz) δ 1.78-1.79 (m,

2H), 1.88 (bs, 2H), 2.74 (bs, 2H),

3.09-3.10 (m, 2H), 3.78 (s, 3H), 3.79

(s, 3H), 7.13-7.15 (m, 1H), 7.23 (s,

1H), 7.68 (d, J= 8.0 Hz, 1H), 7.81 (t,

F₃C J= 8.4 Hz, lH), 7.93 (d, J= 8.0 Hz,

methyl 4-[l-[2-chloro-6- 1H), 7.98 (d, J= 8.0 Hz, 1H)

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol-

3-yl]-2-methoxy-benzoate

A-27 COOH LCMS: m/z 479.0 (M+l)⁺. ¾ NMR INT- 1 -IX

(DMSO-t/,5, 400 MHz) δ 1.78-1.79 (m,

2H), 1.88 (bs, 2H), 2.74 (bs, 2H),

3.09-3.10 (m, 2H), 3.78 (s, 3H), 7.10- 7.21 (m, 1H), 7.21 (s, 1H), 7.66 (d, J =

7.2 Hz, 1H), 7.81 (t, J= 8.0 Hz, 1H),

F₃C 7.93 (t, J= 7.6 Hz, 1H), 7.98 (d, J =

4-[l-[2-chloro-6- 8.4 Hz, 1H), 12.78 (s, 1H)

4- [ 1 -(2-chloro-6-methyl- benzoyl)-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid

A-31 LCMS: m/z 423.1 (M+l)⁺. ^lH NMR INT-1- DMSO-d₆, 400 MHz) δ 1.31 (t, J = VIII

6.8 Hz, 3H), 1.78-1.79 (m, 2H), 1.86-

1.87 (m, 2H), 2.21 (s, 3H), 2.71-2.72

(m, 2H), 3.13-3.15 (m, 2H), 4.31 (q, J

= 6.8 Hz, 2H), 7.33-7.35 (m, 1H),

7.41-7.47 (m, 2H), 7.70 (d, J= 8.0 Hz, ethyl 4-[l-(2-chloro-6- 2H), 8.00 (d, J= 8.4 Hz, 2H)

methyl -benzoyl) -4,5,6,7- tetrahydroindazol-3 - yl]benzoate

A-32 COOH LCMS: m/z 413.0 (M+l)⁺. ^lH NMR INT-1-

(DMSO-rf_tf, 400 MHz) δ 1.73-1.75 (m, VIII

2H), 1.87-1.89 (m, 2H), 2.20 (s, 3H),

2.47-2.51 (m, 2H), 3.14-3.16 (m, 2H),

7.31-7.33 (m, 1H), 7.39-7.44 (m, 2H),

7.53 (t, J= 7.4 Hz, 1H), 7.74-7.77 (m,

1H), 7.81 (dd, J= 8.4, 1.2 Hz, 1H),

4- [ 1 -(2-chloro-6-methyl- 13.65 (s, 1H)

benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-33 COOMe LCMS: m/z 427.0 (M+l)⁺. ¾ NMR INT-1-

(DMSO-t/,5, 400 MHz) δ 1.73 (bs, 2H), VIII

1.88 (bs, 2H), 2.21 (s, 3H), 2.49-2.51

(m, 2H), 3.14-3.15 (m, 2H), 3.87 (s,

3H), 7.31-7.30 (m, 1H), 7.39-7.44 (m,

2H), 7.57 (t, J= 7.6 Hz, 1H), 7.78- 7.85 (m, 2H)

3-yl]benzoic acid

A-45 COOEt LCMS: m/z 539.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.32 (t, J =

7.6 Hz, 3H), 1.72-1.75 (m, 2H), 1.86- 1.89 (m, 2H), 2.46-2.51 (m, 2H), 3.12

(t, J = 5.2 Hz, 2H), 4.33 (q, J = 7.6

Hz, 2H), 7.52 (t, J= 7.6 Hz, 1H), 7.70 F₃C (t, J = 8.0 Hz, 1H), 7.78 (dd, J= 1.6, ethyl 4-[l-[2-bromo-6- 9.2 Hz, 1H), 7.83 (dd, J= 1.6, 6.8 Hz, (trifluoromethyl)benzoyl] - 1H), 7.95 (d, J= 8.0 Hz, 1H), 8.10 (d, 4,5,6,7-tetrahydroindazol- J= 8.4 Hz, lH)

3 -yl] -3 -fluoro-benzoate

A-46 COOH LCMS: m/z 539.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-^, 400 MHz) δ 1.72-1.76 (m,

2H), 1.85-1.90 (m, 2H), 2.46-2.50 (m,

2H), 3.11 (t, J = 5.2 Hz, 2H), 7.49 (t, J

= 7.6 Hz, 1H), 7.70 (t, J= 7.6 Hz,

1H), 7.74 (dd, J= 1.6, 6.8 Hz, 1H),

F₃C 7.81 (dd, J= 1.6, 6.8 Hz, 1H), 7.95 (d,

4-[l-[2-bromo-6- J= 8.0 Hz, lH), 8.10 (d, J= 8.0 Hz, (trifluoromethyl)benzoyl] - 1H), 13.41 (s, 1H)

4,5,6,7-tetrahydroindazol- 3-yl]-3-fluoro-benzoic acid

A-47 COOEt LCMS: m/z 457.2 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.32 (t, J =

6.8 Hz, 3H), 1.72-1.75 (m, 2H), 1.83- 1.87 (m, 2H), 2.46-2.51 (m, 2H), 3.09

-3.11 (m, 2H), 3.78 (s, 3H), 4.33 (q, J

= 6.8 Hz, 2H), 7.16 (t, J= 8.0 Hz,

o 2H), 7.47-7.57 (m, 2H), 7.78 (d, J =

\

8.0 Hz, 1H), 7.83 (d, J= 8.0 Hz, 1H) ethyl 4-[l-(2-chloro-6- methoxy-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

A-48 LCMS: m/z 529.2 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 1.71-1.75 (m,

2H), 1.83-1.87 (m, 2H), 2.46-2.49 (m,

2H), 3.09 -3.11 (m, 2H), 3.78 (s, 3H),

7.16 (t, J= 8.0 Hz, 2H), 7.47-7.54 (m,

2H), 7.75 (dd, J= 1.6, 6.8 Hz, 1H),

7.81 (dd, J= 1.6, 6.8 Hz, 1H), 13.30

(s, 1H)

4- [ 1 -(2-chloro-6-methoxy- benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-49 COOH LCMS: m/z 443.8 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 1.73-1.75 (m,

2H), 1.86-1.91 (m, 2H), 2.46-2.49 (m,

2H), 3.16 (t, J= 6.0 Hz, 2H), 7.43 (t, J

= 8.0 Hz, 1H), 7.70 (t, J= 8.0 Hz,

1H), 7.76 (dd, J= 1.2, 8.0 Hz, lH),

0₂N 7.86 (t, J= 8.0 Hz, 1H), 8.13 (d, J =

4- [ 1 -(2-chloro-6-nitro- 8.0 Hz, 1H), 8.34 (dd, J= 1.2, 8.0 Hz, benzoyl)-4,5,6,7- 1H), 13.41 (s, 1H)

tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-50 COOEt LCMS: m/z 472.2 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.31 (t, J =

6.8 Hz, 3H), 1.74-1.76 (m, 2H), 1.86- 1.91 (m, 2H), 2.46-2.51 (m, 2H), 3.13

-3.16 (m, 2H), 4.32 (q, J = 6.8 Hz,

2H), 7.51 (t, J= 8.0 Hz, 1H), 7.75- 0₂N 7.88 (m, 3H), 8.13 (d, J= 8.8 Hz, 1H), ethyl 4-[l-(2-chloro-6- 7.85 (d, J= 8.8 Hz, 1H) nitro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

A-51 COOH LCMS: m/z 425.8 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 1.78-1.81 (m,

2H), 1.83-1.90 (m, 2H), 2.72 (t, J =

5.2 Hz, 2H), 3.15 (t, J = 5.2 Hz, 2H),

7.62 (d, J= 8.4 Hz, 2H), 7.89 (t, J =

8.0 Hz, 1H), 7.96 (d, J= 8.0 Hz, 2H),

0₂N 8.14 (dd, J= 1.2, 7.2 Hz, 1H), 8.37

4- [ 1 -(2-chloro-6-nitro- (dd, J= 1.2, 7.2 Hz, 1H), 13.01 (s, 1H) benzoyl)-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid

A-52 LCMS: m/z 425.8 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.31 (t, J =

5.6 Hz, 3H), 1.76-1.81 (m, 2H), 1.86-

1.90 (m, 2H), 2.72 (t, J= 5.6 Hz,

2H), 3.15 (t, J= 5.6 Hz, 2H), 4.31 (q,

J= 5.6 Hz, 2H), 7.65 (d, J= 8.0 Hz,

2H), 7.89 (t, J= 8.0 Hz, 1H), 7.99 (d, ethyl 4-[l-(2-chloro-6- J= 8.0 Hz, 2H), 8.15 (dd, J= 1.2, 7.6 nitro-benzoyl)-4,5,6,7- Hz, 1H), 8.36 (dd, J= 1.2, 7.6 Hz, 1H) tetrahydroindazol-3 - yl]benzoate

A-58 LCMS: m/z 465.9 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 1.31 (t, J =

7.2 Hz, 3H), 1.77-1.90 (m, 4H), 2.68- 2.72 (m, 4H), 2.87-2.91 (m, 2H), 3.06- 3.15 (m, 2H), 3.32-3.42 (m, 2H), 3.43- 3.46 (m, 2H), 4.31 (q, J= 7.2 H, 2H),

7.35 (d, J= 8.0 Hz, 2H), 7.53 (t, J =

8.0 Hz, 1H), 7.67 (d, J= 8.4 Hz, 2H), ethyl 4-[l-(2-chloro-6- 7.98 (d, J= 8.4 Hz, 2H)

morpholino-benzoyl)- 4,5,6,7-tetrahydroindazol- 3-yl]benzoate

A-59 LCMS: m/z 427.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t 400 MHz) δ 1.10 (t, J =

6.8 Hz, 3H), 1.74-1.75 (m, 2H), 1.88

(bs, 2H), 2.45-2.50 (m, 2H), 2.51-2.56

(m, 2H), 3.14-3.17 (m, 2H), 7.36-7.41

(m, 2H), 7.45-7.52 (m, 2H), 7.75 (dd,

J= 10.8, 1.6 Hz, lH), 7.81(dd, J= 8.0,

4-[l-(2-chloro-6-ethyl- 1.6 Hz, 1H), 13.20 (bs, 1H)

benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

COOH LCMS: m/z 453.1 (M+l)⁺. ¾ NMR INT- 1 -II

A-60 (DMSO-t 400 MHz) δ 1.70-1.75 (m,

2H), 1.87-1.88 (m, 2H), 2.49-2.52 (m,

2H), 3.12-3.18 (m, 2H), 7.55-7.59 (m,

2H), 7.76 (dd, J= 10.8, 1.6 Hz, 1H),

7.82-7.88 (m, 2H), 12.82 (bs, 1H) CI

4-[l-(3,6-dichloro-2- fluoro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

LCMS: m/z 453.1 (M+l)⁺. ¾ NMR INT- 1 -II

A-61 DMSO-d₆, 400 MHz) δ 1.57 (bs, IH),

1.69-1.76 (m, 3H), 2.32-2.33 (m, IH),

2.41-2.45 (m, IH), 2.78 (bs, IH),

2.99-3.03 (m, IH), 3.88 (s, 3H), 7.25- 7.27 (m, 2H), 7.33-7.38 (m, 3H), 7.45- 7.47 (m, IH), 7.54 (t, J = 7.6 Hz, IH),

7.61-7.63 (m, 2H), 7.79 (dd, J= 10.8, methyl 4-[l-(2-chloro-6- 1.6 Hz, IH), 7.85 (dd, J= 8.0, 1.6 Hz, phenyl-benzoyl)-4,5,6,7- IH).

tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

A-62 COOH LCMS: m/z 477.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-^, 400 MHz) δ 1.57 (bs, IH),

1.69-1.76 (m, 3H), 2.31-2.33 (m, IH),

2.42-2.45 (m, IH), 2.67-2.78 (m, IH),

2.98 (bs, IH), 7.25-7.28 (m, 2H),

7.32-7.39 (m, 3H), 7.45-7.49 (m, IH),

7.51 (t, J= 8.0 Hz, IH), 7.61-7.62 (m,

2H), 7.74 (dd, J= 10.8, 1.6 Hz, IH),

4- [ 1 -(2-chloro-6-phenyl- 7.83 (dd, J= 8.0, 1.6 Hz, IH), 11.86 benzoyl)-4,5,6,7- (s, IH)

tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-63 COOH LCMS: m/z 439.2 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 0.63-0.69 (m,

3H), 0.73-0.76 (m, 1H), 0.78-0.89 (m,

3H), 1.71-1.89 (m, 2H), 2.46-2.52 (m,

2H), 3.16 (bs, 2H), 7.05-7.06 (m, 1H),

7.36-7.343 (m, 2H), 7.52 (t, J= 7.6

Hz, 1H), 7.75 (dd, J= 10.4, 1.6 Hz,

1H), 7.82 (dd, J= 8.0, 1.6 Hz, 1H),

4-[l-(2-chloro-6- 12.79 (s, 1H).

cyclopropyl-benzoyl)- 4,5,6,7-tetrahydroindazol- 3-yl]-3-fluoro-benzoic acid

A-64 COOMe LCMS: m/z 453.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-tfc, 400 MHz) δ 0.66-0.71 (m,

2H), 0.72-0.78 (m, 1H), 0.79-0.88 (m,

1H), 0.90-1.72 (m, 3H), 1.75-1.89 (m,

2H), 2.42-2.50 (m, 2H), 3.16 (bs, 2H),

3.86 (s, 3H), 7.05 (d, J= 6.8 Hz, 1H),

7.36-7.343 (m, 2H), 7.56 (t, J= 7.6

Hz, 1H), 7.79 (dd, J= 10.4, 1.6 Hz,

methyl 4 ^Ψ-[l-(2-chloro-6- 1H), 7.79 (dd, J= 8.0, 1.6 Hz, 1H).

cyclopropyl-benzoyl)- 4,5,6,7-tetrahydroindazol- 3 -yl] -3 -fluoro-benzoate

A-65 COOH LCMS: m/z 453.2 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.74-1.76 (m,

2H), 1.87-1.89 (m, 2H), 2.49-2.52 (m,

2H), 3.13 (t, J= 8.4 Hz, 2H), 7.54 (t, J

= 8.0 Hz, 1H), 7.65-7.73 (m, 2H), 7.75

(m, 1H), 7.82 (dd, J= 7.6, 1.2 Hz,

1H), 12.78 (bs, 1H)

F

4-[l-(2,6-dichloro-3- fluoro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

COOH LCMS: m/z 479.1 (M+l)⁺. ¾ NMR INT- 1 -II

A-66 DMSO-d₆, 400 MHz) δ 1.74-1.75 (m,

2H), 1.87-1.89 (m, 2H), 2.49-2.52 (m,

2H), 3.12-3.14 (m, 2H), 7.47-7.54 (m,

2H), 7.64-7.66 (m, 1H), 7.74-7.78 (m,

2H), 7.82 (dd, J= 7.6, 1.2 Hz, 1H),

Br 12.76 (bs, 1H)

4- [ 1 -(2-bromo-6-chloro- benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-67 COOH LCMS: m/z 435 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 1.73-1.74 (m,

2H), 1.87-1.88 (m, 2H), 2.48-2.53 (m,

2H), 3.12 (bs, 2H), 7.55-7.63 (m, 3H),

7.75-7.84 (m, 1H), 7.83 (dd, J= 7.6,

1.6 Hz, 1H), 12.76 (bs, 1H)

4-[l-(2-chloro-4,6- difluoro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-68 COOH LCMS: m/z 392.7 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.73-1.74 (m,

2H), 1.86-1.87 (m, 2H), 2.13 (s, 6H),

2.46-2.51 (m, 2H), 3.15-3.16 (m, 2H),

7.12 (d, J= 7.6 Hz, 2H), 7.28(t, J =

8.0 Hz, 1H), 7.54 (t, J= 8.0 Hz, 1H),

7.74 (dd, J= 10.8, 1.2 Hz, 1H), 7.80

4-[l-(2,6- (dd, J= 7.6, 1.2 Hz, 1H), 13.20 (bs, dimethylbenzoyl)-4,5,6,7- 1H)

tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-69 COOMe LCMS: m/z 448.7 (M+l)⁺. ¾ NMR INT- 1 -II

(OMSO-d₆, 400 MHz) δ 1.74-1.76 (m,

2H), 1.88-1.89 (m, 2H), 2.50-2.52 (m,

2H), 3.14 (bs, 2H), 3.89 (s, 3H), 7.55-

7.64 (m, 2H), 7.72-7.88 (m, 3H)

CI

methyl 4-[l-(6-chloro-2,3- difluoro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

A-70 LCMS: m/z 435 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.74-1.75 (m,

2H), 1.88-1.89 (m, 2H), 2.49-2.52 (m,

2H), 3.13 (b s, 2H), 7.54-7.60 (m, 2H),

7.70-7.79 (m, 2H), 7.83 (dd, J= 8.4,

1.6 Hz, 1H), 12.65 (bs, 1H)

4-[l-(6-chloro-2,3- difluoro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

LCMS: m/z 449.5 (M+l)⁺. ¾ NMR INT- 1 -II

A-71 (DMSO-t/,5, 400 MHz) δ 1.78 (bs, 2H),

1.86-1.88 (m, 2H), 2.72 (bs, 2H),

3.10-3.11 (m, 2H), 7.80-7.84 (m, 1H),

7.93-8.0 (m, 4H), 8.54 (s, 1H)

5-[l-[2-chloro-6-

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol- 3-yl]pyridine-2-carboxylic

acid

COOH LCMS: m/z 435 (M+l)⁺. ¾ NMR INT- 1 -II

A-72 (DMSO-t/,5, 400 MHz) δ 1.74-1.75

(m, 2H), 1.89-1.90 (m, 2H), 2.50-2.51

C (m, 2H), 3.13 (bs, 2H), 7.50-7.59 (m,

N c,

2H), 7.69-7.82 (m, 2H), 7.83 (dd, J =

1.6, 8.0Hz, 1H), 13.23 (bs, 1H)

4-[l-(2-chloro-3,6- difluoro-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-73 COOH LCMS: m/z 424.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.71-1.82 (m,

2H), 1.90-1.99 (m, 2H), 2.48-2.52 (m,

2H), 3.21-3.25 (m, 2H), 7.48-7.56 (m,

2H), 7.57-7.69 (m, 2H), 7.78-7.84 (m,

2H), 13.01 (s, 1H)

NC

4- [ 1 -(2-chloro-6-cyano- benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

A-74 COOEt LCMS: m/z 452.1 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-t/,5, 400 MHz) δ 1.39 (t, J =

7.2 Hz, 3H), 1.78-1.82 (m, 2H), 1.94-

1.96 (m, 2H), 2.50-2.53 (m, 2H), 3.22-

3.24 (m, 2H), 4.38 (q, J = 7.2 Hz,

2H), 7.49-7.54 (m, 2H), 7.66-7.77 (m,

NC 2H), 7.77 (dd, J= 1.6, 8.0 Hz, 1H),

ethyl 4-[l-(2-chloro-6- 7.80 (dd, J= 8.0 Hz, 1H)

cyano-benzoyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

Synthesis B-2: 4-[l-(2,6-dichlorobenzoyl)-6,6-dimethyl-4-oxo-3a,5,7,7a- tetrahydroindazol-3-yl]benzoic acid

OMe

B-1 B-2

Step I: methyl 4-(4,4-dimethyl-2,6-dioxo-cyclohexanecarbonyl)benzoate

To a stirred mixture of 5,5-dimethylcyclohexane-l,3-dione INT-2-1 (5.0 g, 35 mmol) and methyl 4-chlorocarbonylbenzoate (9.84 g, 46 mmol) in toluene was added N,N- dimethylpyridin-4-amine (0.87 g, 7 mmol) and reaction mixture was heated 100 °C for 4 h. After consumption of starting material on TLC, reaction mixture was cooled; water was added and extracted with EtOAc (30 x 3 mL). Combined organic layer was dried over NaiSO/_t, filtered and the solvent was evaporated under reduced pressure. The reaction was dissolved in acetonitrile and triethyl amine (9.9 mL, 71 mmol) was added and stirred at room temperature for overnight. After completion, reaction mixture was evaporated under reduced pressure. The crude product was taken further for next step without purification. LCMS: m/z 303 (M+l)⁺.

Step II: methyl 4-(6,6-dimethyl-4-oxo-5,7-dihydro-lH-indazol-3-yl)benzoate

To a stirred mixture of methyl 4-(4,4-dimethyl-2,6-dioxo-cyclohexanecarbonyl)benzoate INT-2-II (3.0 g, 9.9 mmol) in ethanol hydrazine hydrate (0.32 g, 9.9 mmol) was added and reaction mixture was stirred at room temperature for 6 h. After completion, reaction mixture was evaporated under reduced pressure. Water was added and extracted with EtOAc (3 x 30 mL). Combined organic layer was washed with saturated brine, dried over NaiSO/t, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (20% EtOAc in hexane) to provide title compound INT 2- III (1.5 g, 41%). LCMS: m/z 301 (M+l)⁺.

Step III: Synthesis B-l: methyl 4-[l-(2,6-dichlorobenzoyl)-6,6-dimethyl-4-oxo-5,7- dihydroindazol-3-yl]benzoate

Title compound was synthesized as described for the synthesis of A-lmethyl 4-[l-(2,6- dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate. LCMS: m/z 473.0 (M+l)⁺. ^!H NMR DMSO-d₆, 400 MHz) δ 1.52 (2, 6H), 2.56 (s, 2H), 3.99 (s, 2H), 3.86 (s, 3H), 7.65-7.71 (m, 3H), 7.88 (d, J= 8.8 Hz, 2H), 7.99 (d, J= 8.8 Hz, 2H)

Step IV: Synthesis B-2: 4-[l-(2,6-dichlorobenzoyl)-6,6-dimethyl-4-oxo-5,7- dihydroindazol-3-yl]benzoic acid

Title compound was synthesized as described for the synthesis of A-2 4-[l-(2,6- dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid. LCMS: m/z 459.0 (M+l)⁺. ^!H NMR (DMSO-rf_fc 400 MHz) δ 1.16 (s, 6H), 2.59 (s, 2H), 3.40 (s, 2H), 7.63-7.71 (m, 3H), 7.45 (d, J= 8.4 Hz, 2H), 7.97 (d, J= 8.4 Hz, 2H), 13.01 (s, 1H)

Following intermediates were synthesized from their corresponding starting materials following similar sequence of procedures as for the preparation of B-2 from INT-2-III

4-{3-[2-chloro-6- 4H)

(trifluoromethyl)benzoyl] -

3,4- diazatricyclo[5.2.1.0{2,6}]de

ca-2(6),4-dien-5- yl}benzoate

B-7 LCMS: m/z 435.1 (M+l)⁺. ¾ NMR INT-2-III

DMSO-d₆, 400 MHz) δ 2.67-2.73

(m, 2H), 2.92 (t, J= 6.8 Hz, 2H),

3.14 (t, J = 6.8 Hz, 2H), 7.68 (d, J =

8.4 Hz, 2H), 7.83-7.87 (m, IH),

7.96-8.03 (m, 4H), 13.05 (s, IH)

4-[l-[2-chloro-6-

(trifluoromethyl)benzoyl] -

5,6-dihydro-4H- cyclopenta[c]pyrazol-3- yl]benzoic acid

B-8 COOMe LCMS: m/z 449.0 (M+l)⁺. 'H NMR INT-2-III

(DMSO-t/,5, 400 MHz) δ 2.63-2.73

(m, 2H), 2.92 (t, J= 7.2 Hz, 2H),

3.14 (t, J= 7.2 Hz, 2H), 3.85 (s,

3H), 7.43 (d, J= 8.8 Hz, 2H), 7.84-

7.88 (m, IH), 7.96-8.03 (m, 4H)

F₃C

methyl 4-[l-[2-chloro-6-

(trifluoromethyl)benzoyl] -

5,6-dihydro-4H- cyclopenta[c]pyrazol-3- yl]benzoate

yl]benzoic acid

B-12 COOMe LCMS: m/z 477.1 (M+l)⁺. ¾ NMR INT-2-III

DMSO-d₆, 400 MHz) δ 1.56-1.58

(m, 4H), 1.75-1.78 (m, 2H), 2.37-

2.39 (m, 2H), 2.62-2.67 (m, 2H),

3.89 (s, 3H), 7.53 (dd, J= 2.0, 4.8

Hz, 2H), 7.77 (t, J= 7.2 Hz, 1H),

7.88 (d, J= 8.4 Hz, 1H), 7.94 (d, J = methyl 4-[l-[2-chloro-6- 8.4 Hz, 1H), 8.07 (dd, J = 2.0, 4.8

(trifluoromethyl)benzoyl] - Hz, 2H)

5,6,7,8-tetrahydro-4H- cyclohepta[c]pyrazol-3- yl]benzoate

B-13 COOH LCMS: m/z 505 (M+l)⁺. ¾ NMR INT-2-III

(DMSO-t/,5, 400 MHz) δ 0.97 (s,

9H), 1.41-1.46 (m, 2H), 2.10-2.13

(m, 1H), 2.55-2.66 (m, 2H), 2.88-

2.93 (m, 1H), 3.24-3.37 (m, 1H),

7.65-7.69 (m, 2H), 7.80-7.84 (m,

F₃C 1H), 7.91-8.08 (m, 4H), 13.10 (s,

4- [5 -tert-butyl- 1 -[2-chloro-6- 1H)

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol-3- yl]benzoic acid

B-14 LCMS: m/z 463 (M+l)⁺. ¾ NMR INT-2-III

(DMSO-t/,5, 400 MHz) δ 1.08-1.10

(m, 3H), 1.50-1.54 (m, 1H), 1.87-

1.99 (m, 2H), 2.35-2.41 (m, 1H),

2.74-2.79 (m, 1H), 3.0-3.05 (m, 1H),

3.23-3.32 (m, 1H), 7.63-7.67 (m,

2H), 7.79-7.84 (m, 1H), 7.92-8.02

4-[l-[2-chloro-6- (m, 4H), 13.1 (s, 1H)

(trifluoromethyl)benzoyl] -5 - methyl-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid

B-15 LCMS: m/z 477 (M+l)⁺. ¾ NMR INT-2-III

DMSO-d₆, 400 MHz) δ 1.08-1.10

(m, 3H); 1.50-1.54 (m, lH); 1.86-

1.99 (m, 2H); 2.35-2.41 (m, lH);

2.74-2.81 (m, 1H); 2.98-3.05 (m,

1H) 3.22-3.32 (m, 1H); 3.85 (s, 3H)

7.66-7.69 (m, 2H); 7.80-7.84 (m, methyl 4-[l-[2-chloro-6- 1H); 7.92-8.01 (m, 4H).

(trifluoromethyl)benzoyl] -5 - methyl-4,5,6,7- tetrahydroindazol-3 - yl]benzoate

B-16 COOH LCMS: m/z 480.9 (M+l)⁺. ¾ NMR INT-2-III

(DMSO-t/,5, 400 MHz) δ 2.23-2.64

(m, 2H); 2.55-2.57 (m, 2H); 3.47 (t,

C ^ci J= 5.2 Hz, 2H); 7.46 (t, J = 7.2 Hz,

1H); 7.71 (d, J= 10.4 Hz, 1H); 3.57- 3.61 (m, 1H); 7.78-7.86 (m, 2H);

F₃C 7.96 (d, J= 8.0 Hz, 1H); 7.01 (d, J =

4-[l-[2-chloro-6- 7.6 Hz, 1H)

(trifluoromethyl)benzoyl] -4- oxo-6,7-dihydro-5H-indazol-

3-yl]-3-fluoro-benzoic acid

B-17 COOH LCMS: m/z 463 (M+l)⁺. ¾ NMR INT-2-III

(DMSO-t/,5, 400 MHz) δ 1.31-1.36

(m, 3H); 1.79-1.93 (m, 4H); 2.71-

2.73 (m, 2H); 3.57-3.61 (m, lH);

7.63-7.66 (m, 2H); 7.74-7.84 (m,

1H); 7.92-8.01 (m, 4H); 13.03 (s,

F₃C 1H). 4-[l-[2-chloro-6- (trifluoromethyl)benzoyl] -7- methyl-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid Synthesis C-2: 4-[3-[2-chloro-6-(trifluoromethyl)benzo;

tetrah droindazol-l-yl]benzoic acid

Step I: [2-chloro-6-(trifluoromethyl)phenyl]-(4,5,6,7-tetrahydro-lH-indazol-3- yl)methanol

To a solution of 3-iodo-4,5,6,7-tetrahydro-lH-indazole INT-l-II (0.5 g, 2.02 mmol) in ether at -78 °C was added 0.8 mL "BuLi (1 M in hexane) and followed by ^lBuLi (2.9 mL hexane solution). The reaction mixture was stirred at -78 °C for 15 min and the allowed to warm to room temperature. Stirring was continued for another 15 min. To that 2-chloro-6- (trifluoromethyl)benzaldehyde (0.41 g, 2.2 mmol) was added. After completion, reaction mixture was cooled to 0 °C and quenched by the addition of saturated aqueous NH₄CI solution (15 mL). The aqueous phase was extracted with EtOAc (3 x 15 mL). The combined organic layer was washed with brine, dried over Na₂S04, filtered and the solvent was removed under educed pressure. The crude product was purified by silica gel column chromatography (30% EtOAc in hexane) to provide title compound INT-3-I (0.41 g, 61%). LCMS: m/z 331 (M+l)⁺.

Step II: [2-chloro-6-(trifluoromethyl)phenyl]-(4,5,6,7-tetrahydro-lH-indazol-3- yl)methanone

To a solution of [2-chloro-6-(trifluoromethyl)phenyl]-(4,5,6,7-tetrahydro-lH-indazol-3- yl)methanol INT-3-I (0.4 g, 0.69 mmol) in 1,4 dioxane was added MnO₂ (0.4 g, 1.3 mmol). The reaction mixture was heated at 100 °C for 1 h. After completion, reaction mixture was cooled to room temperature, filtered through celite bed and the celite bed washed with CH₂CI₂. The organic solvent was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (20% EtOAc in hexane) to provide title compound INT-3-II (0.3 g, 45%). LCMS: m/z 329 (M+l)⁺.

Step III: Synthesis C-l: ethyl 4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrahydroindazol-l-yl]benzoate

A mixture of [2-chloro-6-(trifluoromethyl)phenyl]-(4,5,6,7-tetrahydro-lH-indazol-3- yl)methanoneINT-3-II (0.1 g, 0.31 mmol) and Cs₂C0₃ (0.19 g, 0.60 mmol) in dry DMF (15 mL) was heated to 100 °C for 30 minutes. To that ethyl 4-fluorobenzoate (0.05 gm, 0.33 mmol) was added and heating was continued for another 3-4 h at 100 °C. After completion of the reaction, it was cooled to room temperature; brine was added and extracted with EtOAc (3 x 15 mL). Combined organic layer was washed with brine, dried over NaiSO/_t, filtered and the solvent was concentrated under reduced pressure to give a crude solid. The crude product was purified by silica gel column chromatography (10 % EtOAc in hexane) to provide title compound C-l (0.12 g, 81%). LCMS: m/z 477.0 (M+l)⁺. ^!H NMR DMSO-d₆, 400 MHz) δ 1.32 (t, J= 7.2 Hz, 3H), 1.74 (bs, 4H), 2.82 (bs, 4H), 4.33 (q, J= 7.2 Hz, 2H), 7.63 (d, J= 8.4 Hz, 2H), 7.74 (d, J = 8.0 Hz, 1H), 7.86-7.92 (m, 2H), 8.07 (d, J= 8.4 Hz, 2H)

Step IV: Synthesis C-2: 4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrahydroindazol-l-yl]benzoic acid

Title compound was synthesized as described for the synthesis of A-2 (2,6-dichlorophenyl)- (3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone. LCMS: m/z 448.9 (M+l)⁺. ^!H NMR (DMSO-£¾, 400 MHz) δ 1.77 (bs, 4H), 2.80 (bs, 4H), 7.58 (d, J = 8.8 Hz, 2H), 7.72 (t, J = 7.6 Hz, 1H), 7.84-7.90 (m, 2H), 8.03 (d, J= 8.4 Hz, 2H), 13.2 (bs, 1H)

Following intermediates were synthesized from their corresponding starting materials following similar sequence of procedures as for the preparation of C-2 from INT-3-II o Structure/IUPAC name Characterization INT used

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol- 1 - yl]pyridine-3-carboxylic acid

C-6 LCMS: m/z 477.9 (M+l)⁺. ¾ NMR INT-3-II

DMSO-d₆, 400 MHz) δ 1.33 (t, J =

6.8 Hz, 3H), 1.78 (bs, 4H), 2.79 (bs,

2H), 3.15 (bs, 2H), 4.34 (q, J= 6.8

Hz, 2H), 7.63 (d, J= 8.4 Hz, 1H),

7.77 (t, J= 8 Hz, 1H), 7.89-7.94 (m,

2H), 8.41 (dd, J= 2.0, 6.8 Hz, lH),

ethyl 6- 8.97 (s, 1H)

[3-[2-chloro-6-

(trifluoromethyl)benzoyl] -

4,5,6,7-tetrahydroindazol- 1 - yl]pyridine-3-carboxylate

C-7 COOEt LCMS: m/z 443.0 (M+l)⁺. ¾ NMR INT-3-II

(DMSO-tfe 400 MHz) δ 1.32 (t, J =

7.2 Hz, 3H), 1.78 (bs, 4H), 2.82 (bs,

4H), 4.33 (q, J= 7.2 Hz, 2H), 7.49- 7.54 (m, 1H), 7.56-7.59 (m, 2H),

7.66 (d, J= 8.8 Hz, 2H), 8.08 (d, J =

CI 8.8 Hz, 2H)

ethyl 4-[3-(2,6- dichlorobenzoyl)-4,5,6,7- tetrahydroindazol- 1 - yl]benzoate

C-8 COOH LCMS: m/z 415.1 (M+l)⁺. ¾ NMR INT-3-II

(DMSO-t/,5, 400 MHz) δ 1.79 (bs,

4H), 2.82 (bs, 4H), 7.50-7.54 (m,

1H), 7.56-7.59 (m, 2H), 7.63 (d, J =

8.4 Hz, 2H), 8.06 (d, J= 8.8 Hz,

2H), 13.20 (bs, 1H)

CI 4- [3 -(2, 6-dichlorobenzoyl) - 4,5,6,7-tetrahydroindazol- 1 - yl]benzoic acid

C-9 COOMe LCMS: m/z 447.1 (M+l)⁺. ¾ NMR INT-3-II

(DMSO-i/_fc 400 MHz) δ 1.78 (bs,

4H), 2.55 (bs, 2H), 2.82 (bs, 2H),

3.89 (s, 3H) 7.47-7.51 (m, 1H),

7.54-7.56 (m, 2H), 7.68 (t, J= 7.2

Hz, 1H), 7.91-7.98 (m, 2H)

CI

methyl 4-[3-(2,6- dichlorobenzoyl)-4,5,6,7- tetrahydroindazol- 1 -yl] -3 - fluoro-benzoate

COOH LCMS: m/z 432.9 (M+l)⁺. ¾ NMR INT-3-II

C-10 ⁰. (DMSO-rf_fc 400 MHz) δ 1.61-1.81

(m, 4H), 2.49-2.50 (m, 2H), 2.75- 2.89 (m, 2H), 7.47-7.51 (m, 1H),

7.54-7.56 (m, 2H), 7.63-7.67 (m,

1H) 7.88-7.92 (m, 2H)

CI

4- [3 -(2, 6-dichlorobenzoyl) - 4,5,6,7-tetrahydroindazol- 1 - yl]-3-fluoro-benzoic acid

C-l l COOH LCMS: m/z 416.2 (M+l)⁺. ¾ NMR INT- 1 -II

(DMSO-rf_fc 400 MHz) δ 1.61-1.63

(m, 2H), 1.69-1,73 (m, 2H), 2.05

(bs, 2H), 2.67 (t, J= 5.2 Hz, 2H),

7.52 (d, J= 8.4 Hz, 2H), 7.78 (d, J =

5.2 Hz, 1H), 7.98 (d, J= 8.4 Hz,

2H), 8.51 (d, J= 5.2 Hz, 1H), 13.01

4- [3 -(2,4-dichloropyridine-3 - (s, 1H)

carbonyl)-4,5,6,7- tetrahydroindol- 1 -yl]benzoic

acid

C-12 COOEt LCMS: m/z 444.2 (M+l)⁺. ¾ NMR INT- 1 -II

DMSO-d₆, 400 MHz) δ 1.35 (t, J =

6.8 Hz, 3H), 1.62-1.65 (m, 2H),

1.71-1,74 (m, 2H), 2.05 (bs, 2H),

2.69 (t, J= 6.8 Hz, 2H), 4.35 (q, J =

6.8 Hz, 1H), 7.56 (d, J= 8.4 Hz,

2H), 7.80 (d, J= 5.2 Hz, 1H), 8.04

ethyl 4-[3-(2,4- (d, J= 8.4 Hz, 2H), 8.54 (d, J= 5.2 dichloropyridine -3 - Hz, 1H)

carbonyl)-4,5,6,7- tetrahydroindol- 1 - yl]benzoate ] Synthesis D-3: 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-fluoro-4,5,6,7- tetrah droindazol-3-yl]benzoic acid

D-3 Step I: Synthesis D-l: methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-hydroxy- 4,5,6,7-tetrahydroindazol-3-yl]benzoate

To a solution of methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-oxo-6,7-dihydro-5H- indazol-3-yl]benzoate B-9 (0.2 g, 0.42 mmol) in methnol (5 mL) was added NaB¾ (0.016 g, 0.42 mmol) at 0 °C and stirred at room temperature for 10 minutes. After completion of the reaction, it was concentrated under reduced pressure. Water was added and extracted with EtOAc (3 x 15 mL). Combined organic layer was washed with brine, dried over NaiSO/_t, filtered and the solvent was concentrated under reduced pressure to give a crude solid. The crude product was purified by silica gel column chromatography (30 % EtOAc in hexane) to provide title compound D-l (0.16 g, 81%). LCMS: m/z 479.0 (M+l)⁺.

Step II: Synthesis D-2: methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-fluoro- 4,5,6,7-tetrahydroindazol-3-yl]benzoate

To a solution of methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-hydroxy-4,5,6,7- tetrahydroindazol-3-yl]benzoate D-l (0.1 g, 0.21 mmol) in DCM:EtOH (5:0.2 mL) was added DAST (0.033 mL, 0.52 mmol) at -78 °C and stirred at room temperature for 2 h. After completion of the reaction, water was added and extracted with CH₂CI₂ (3 x 15 mL). Combined organic layer was washed with brine, dried over NaiSO/_t, filtered and the solvent was concentrated under reduced pressure to give a crude solid. The crude product was purified by silica gel column chromatography (15 % EtOAc in hexane) to provide title compound D-2 (0.81 g, 78 %). LCMS: m/z 481.1 (M+l)⁺. ^lH NMR DMSO-d₆, 400 MHz) δ 1.86-1.99 (m, 3H), 2.24 (bs, 1H), 2.99-3.04 (m, 1H), 3.37 (s, 1H), 3.63 (s, 3H), 5.79 (dd, J = 8.4, 11.6 Hz, lH), 7.74-7.77 (m, 2H), 7.85 (t, J= 8 Hz, 1H), 7.95-8.05 (m, 4H).

Step III: Synthesis D-3: 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-fluoro-4,5,6,7- tetrahydroindazol-3-yl]benzoic acid

Title compound was synthesized as described for the synthesis of A-2 (2,6-dichlorophenyl)- (3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone. LCMS: m/z 467.0 (M+l)⁺. ^!H NMR (DMSO-£¾, 400 MHz) δ 1.86-2.01 (m, 3H), 2.18-2.24 (m, 1H), 2.99-3.06 (m, 1H), 3.36-3.42 (m, 1H), 5.79 (dd, J= 8.0, 11.6 Hz, 1H), 7.72-7.75 (m, 2H), 7.83 (t, J = 8 Hz, 1H), 7.95-7.97 (m, 4H), 13.01 (s, 1H)

Following intermediates were synthesized from their corresponding starting materials following similar sequence of procedures as for the preparation of D-3 from D-2 No Structure/IUPAC name Characterization INT used

D-4 COOH LCMS: m/z 465.1 (M+l)⁺. ¾ NMR D-l

DMSO-d₆, 400 MHz) δ 1.74-1.77

OH (m, 1H), 1.91-1.99 (m, 2H), 2.03-

2.07 (m, 1H), 2.89-2.95 (m, 1H),

ULN'^{N CI} 3.24-3.28 (m, 1H), 4.76-4.78 (m,

1H), 5.38 (t, J= 6.8 Hz, 1H), 7.83

(t, J= 8 Hz, 1H), 7.90-8.03 (m, 6H),

4-[l-[2-chloro-6- 13.01 (bs, 1H)

(trifluoromethyl)benzoyl] -4- hydroxy-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid ] Synthesis of E-1: sodium 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrahydroindazol-3-yl]-3-fluoro-benzoate

tetrahydroindazol-3-yl]-3-fluoro-benzoate

To a suspension of 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3- yl]-3-fluoro-benzoic acid A-18 (0.05 g, 0.11 mmol) in water (5 mL) NaOH (0.005 g, 0.11 mmol) in water (1 mL) at 0 °C was added and stirred at room temperature for 30 min. After completion of the reaction, it was concentrated under reduced pressure. The crude reaction mixture was washed with pentane and diethyl ether and the solid was dried to afford the title compound E-l (0.05 g, 95%). LCMS: m/z 467.1 (M-Na+1)⁺. ¾ NMR (DMSO-^, 400 MHz) δ 1.72-1.74 (m, 2H), 1.86-1.89 (m, 2H), 2.44-2.47 (m, 2H), 3.09-3.11 (m, 2H), 7.21 (t, J= 7.2 Hz, 1H), 7.56 (dd, J= 10.8, 1.2 Hz, 1H), 7.65 (dd, J= 10.8, 1.2, 1H), 7.78 (t, J= 8.4 Hz, 1H), 7.91 (d, J= 7.6 Hz, 1H), 7.95 (d, J= 7.6 Hz, 1H).

Synthesis F-1: [2-chloro-6-(trifluoromethyl)phenyl]-[3-(2-fluoro-4-methyl- phenyl)-4,5,6,7-tetrahydroindazol-l- l]methanone

A-14 F-1

Step I: [2-chloro-6-(trifluoromethyl)phenyl]-[3-(2-fluoro-4-methyl-phenyl)-4,5,6,7- tetrahydroindazol-l-yl]methanone

To a stirred mixture of 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol- 3-yl]-3-fluoro-benzoic acid A-14 (0.200 g, 0.43 mmol), methyl amine in 2M in THF (0.4 ml, 0.86 mmol) and triethylamine (0.12 mL, 0.86 mmol) in dry CH₂CI₂ (5 mL) was added at room temperature for 15 min. To that Propylphosphonic anhydride (T3P) (0.27 mL, 0.86 mmol) was added. The reaction mixture was stirred overnight at room temperature. After completion of the reaction, it was quenched by the addition of water and aqueous phase was extracted with CH₂CI₂ (3 x 10 mL). Combined organic layer was washed with saturated aqueous NaHCC>3 solution, brine, dried over Na₂SC>4, filtered and the solvent was removed to give a solid. The crude product was purified by silica gel column chromatography (50% EtOAc in hexane) to provide title compound F-1 (0.50 g, 28%). LCMS: m/z 480 (M+l)⁺. ^!H NMR (DMSO- ₆, 400 MHz) δ 1.78-1.79 (m, 2H), 1.84-1.87 (m, 2H), 2.70-2.73 (m, 2H), 2.76 (d, J = 4.4 Hz, 3H), 3.07-3.11 (m, 2H), 7.33 (d, J = 8.4 Hz, 1H), 7.43 (dd, J = 8.0.8, 1.6 Hz, 1H), 7.67 (t, J = 8.0, lH), 7.82 (t, J = 8.4 Hz, lH), 7.94 (d, J = 8.0 Hz, lH), 7.99 (d, J = 8.4 Hz, 1H), 8.24-8.26 (m, 1H).

Following compound was prepared from its corresponding intermediate using the same sequence of procedures as used for preparation of Example F-1 from A-14:

Synthesis G-2: 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,4-difluoro-6,7- dihy dro-5H-indazol-3-yl] benzoic acid

B-9 G-1 ^

Step I: Synthesis Gl: methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,4-difluoro- 6,7-dihydro-5H-indazol-3-yl]benzoate

Methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-oxo-6,7-dihydro-5H-indazol-3- yljbenzoate B-9 (0.05 g, 0.105 mmol) in deoxofluor (0.038 mL, 0.21 mmol) was heated at 65 °C for 12 h. After completion of the reaction, it was quenched by the addition of saturated aqueous sodium bicarbonate solution at 0 °C and extracted with EtOAc (3 x 10 mL). Combined organic layer was washed with saturated aqueous NaHCC>3 solution, brine, dried over NaiSO/_t, filtered and the solvent was removed to give a solid. The crude product was purified by silica gel column chromatography (30% EtOAc in hexane) to provide title compound G-1 (0.06 g, 12 %). LCMS: m/z 499.1 (M+l)⁺. ¾ NMR (DMSO-^, 400 MHz) δ 2.11 (bs, 2H), 2.341 (bs, 2H), 3.27-3.28 (m, 2H), 3.86 (s, 3H), 7.74 (d, J = 8.4 Hz, 2H), 7.86 (t, J= 8.0 Hz, 1H), 7.98 (d, J= 7.6, 1H), 8.02 (d, J= 8.0 Hz, 3H)

Step II: 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,4-difluoro-6,7-dihydro-5H-indazol- 3-yl] benzoic acid

Title compound was synthesized as described for the synthesis of A-2 (2,6-dichlorophenyl)- (3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone. LCMS: m/z 485 (M+l)⁺. ^!H NMR (DMSO- ₅, 400 MHz) δ 2.08-2.1 1 (m, 2H); 2.34-2.37 (m, 1H); 3.27-3.32 (m, 2H); 7.66- 7.73 (m, 2H); 7.80-7.91 (m, 2H); 7.98-8.04 (m, 3H); 13.12 (bs, 1H).

Following compound was prepared from its corresponding intermediate using the same sequence of procedures as used for preparation of Example G-2 from B-9

Synthesis H-2: 4-[3-(2,6-dichlorobenzoyl)-4-oxo-6,7-dihydro-5H-indol-l- yl] benzoic acid

H-1

Step I: ethyl 4-(4-oxo-6,7-dihydro-5H-indol-l-yl)benzoate

A mixture of l,5,6,7-tetrahydroindol-4-one(INT-4-I) (2 g, 14.2 mmol) and Cs₂C0₃ (4.6 g, 14.2 mmol) in dry DMF (30 mL) was heated to 100 °C for 30 minutes. To that ethyl 4- fluorobenzoate (2.69 gm, 15.7 mmol) was added and heating was continued for another 12 h at 100 °C. After completion of the reaction, it was cooled to room temperature; brine was added and extracted with EtOAc (3 x 15 mL). Combined organic layer was washed with brine, dried over NaiSO/_t, filtered and the solvent was concentrated under reduced pressure to give a crude solid. The crude product was purified by silica gel column chromatography (5 % EtOAc in hexane) to provide title compound INT-4-II (1 g, 25%). LCMS: m/z 284 (M+l)⁺. Step II: Synthesis H-1: ethyl 4-[3-(2,6-dichlorobenzoyl)-4-oxo-6,7-dihydro-5H-indol-l- yljbenzoate

To a suspension of aluminum chloride (0.6 g, 4.5 mmol) in CH₂CI₂ (15 ml) was added 2, 6- dichloro-benzoyl chloride (0.47 g, 2.3 mmol) and the mixture was stirred at room temperature for 1 h. A solution of ethyl 4-(4-oxo-6,7-dihydro-5H-indol-l-yl)benzoate INT-4-II (0.2 g, 0.7 mmol) in CH₂CI₂ (5 ml) was drop wise added and the reaction mixture was stirred for 12 h. After completion of the reaction, it was poured into ice water and extracted with CH₂CI₂ (3 x 10 ml). The combined organic layer was washed with brine, dried over MgSC>4 and concentrated to under reduced pressure. The crude product was purified by silica gel column chromatography (10% EtOAc in hexane) to provide title compound H-1 (0.16 g, 52%). LCMS: m/z 456 (M+l)⁺. ^!H NMR (DMSO-^, 400 MHz) δ 1.36 (t, J = 4.8 Hz, 3H), 2.03- 2.06 (m, 2H), 2.43-2.46 (m, 2H), 2.63 (t, J = 4.8 Hz, 2H), 4.37 (q, J = 6.8 Hz, 2H), 6.83 (s, 1H), 7.61 (t, J = 6.4 Hz, 4H), 8.13 (d, J= 8.4 Hz, 2H).

Step III: Synthesis H-2: 4-[3-(2,6-dichlorobenzoyl)-4-oxo-6,7-dihydro-5H-indol-l- yl] benzoic acid Title compound was synthesized as described for the synthesis of A-2 (2,6-dichlorophenyl)- (3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone. LCMS: m/z 429 (M+l)⁺. ^!H NMR DMSO-d₆, 400 MHz) δ 2.06-2.30 (m, 2H), 2.43-2.46 (m, 2H), 2.62-2.65 (m, 2H), 6.80 (s, 1H), 7.53-7.61 (m, 5H), 8.18 (t, J= 4.4 Hz, 2H), 13.24 (bs, 1H). Synthesis 1-3: 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrah dropyrazolo[4,3-b]pyridin-3-yl]benzoic acid

Step I: tert-butyl 2-(4-methoxycarbonylbenzoyl)-3-oxo-piperidine-l-carboxylate

Title compound was synthesized as described for the synthesis of INT-2-II (methyl 4-(4,4- dimethyl-2,6-dioxo-cyclohexanecarbonyl)benzoate)LCMS: m/z 362.1 (M+l)⁺.

Step II: tert-butyl 3-(4-methoxycarbonylphenyl)-l,5,6,7-tetrahydropyrazolo[4,3- b] pyridine-4-carboxylate

Title compound was synthesized as described for the synthesis of INT-2-III (methyl 4-(6,6- dimethyl-4-oxo-5,7-dihydro-lH-indazol-3-yl)benzoate)LCMS: m/z 358.1 (M+l)⁺.

Step III: Synthesis 1-1: tert-butyl l-[2-chloro-6-(trifluoromethyl)benzoyl]-3-(4- methoxycarbonylphenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridine-4-carboxylate Title compound was synthesized as described for the synthesis of B-l (methyl 4-[l-(2,6- dichlorobenzoyl)-6,6-dimethyl-4-oxo-5,7-dihydroindazol-3-yl]benzoate). LCMS: m/z 563.9 (M+l)⁺. ^!H NMR (DIVISOR, 400 MHz) δ 0.98 (bs, 9H), 1.95 (bs, 2H), 3.23 (t, J = 6.8 Hz, 2H), 3.84 (bs, 2H), 3.85 (s, 3H), 7.60 (d, J = 8.4 Hz, 2H), 7.84 (t, J = 8.4 Hz, 1H), 7.94-8.01 (m, 4H)

Step IV: Synthesis 1-2: 4-[4-tert-butoxycarbonyl-l-[2-chloro-6-

(trifluoromethyl)benzoyl]-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-3-yl]benzoic acid

Title compound was synthesized as described for the synthesis of A-2 (2,6-dichlorophenyl)- (3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone). LCMS: m/z 550.1 (M+l)⁺. ^!H NMR (DMSO-£¾, 400 MHz) δ 0.98 (bs, 9H), 1.95 (bs, 2H), 3.23 (t, J = 6.4 Hz, 2H), 3.67 (bs, 2H), 7.57 (d, J= 8.4 Hz, 2H), 7.83 (t, J= 8.4 Hz, 1H), 7.94-8.01 (m, 4H), 13.01 (bs, 1H)

Step V: Synthesis 1-3: 4- [l-[2-chloro-6-(trifluoromethyl)benzoyl] -4,5,6,7- tetrahydropyrazolo[4,3-b]pyridin-3-yl]benzoic acid

4-[4-tert-butoxycarbonyl- 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -6,7-dihydro-5H- pyrazolo[4,3-b]pyridin-3-yl]benzoic acid (1-2) (0.025 g) was dissloved in 1M HCl in dioxane (2 mL) and stirred at room temperature for 12 h. After completion of reaction (monitored by TLC), reaction mixture was concentrated under reduced pressure to give a crude solid. It was washed with pentane and dried to provide title compound 1-3. (0.015g). LCMS: m/z 449.8 (M+l)⁺. ^lH NMR (DMSO-t/,5, 400 MHz) δ 1.80 (bs, 2H), 3.11-3.18 (m, 4H), 7.73 (d, J = 8.4 Hz, 2H), 7.80 (t, J= 8.4 Hz, 1H), 7.92-7.97 (m, 4H), 12.91 (bs, 1H).

Synthesis J-l : 4-[l- [2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H- indazole-7,l'-c clopentane]-3-yl]benzoic acid

INT-6-V

Step I: spiro[4.5]decan-10-one

To a solution of cyclohexanone (INT-6-I) (2.0 g, 20 mmol) in toluene (30 mL) was added potassium tert. butoxide (5 g, 45 mmol) and stirred 1 h at room temperature. 1, 4 dibromo butane (9.6 g, 45 mmol) was added into reaction mixture and heated at 100 °C for 12 h. After completion of reaction monitored by TLC, reaction mixture was cooled down to room temperature and aqueous IN HC1 (15 mL) was added and extracted with diethyl ether (3 x 15 mL). The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified on combifalsh system with a gradient of 5 to 10% ethyl acetaie-hexanes to obtain the desired product ίΝΤ-6-Ιί(1 g, 32%). ^!H NMR (DMSO-t^, 400 MHz) δ 1.31 -1.39 (m, 2H), 1.43-1.54 (m, 4H), 1.55- 1.57 (m, 4H), 1.66-1.69 (m, 2H), 1.95-1.1.99 (m, 2H), 2.00-2.34 (m, 2H)

Step II: methyl 4-(10-oxospiro[4.5]decane-9-carbonyl)benzoate

Title compound was synthesized as described for the synthesis of INT-2-II (methyl 4-(4,4- dimethyl^^-dioxo-cyclohexanecarbony benzoate)¹!! NMR (OMSO-d₆, 400 MHz) δ 1.63- 1.74 (m, 8H), 1.82-1.93 (m, 4H), 2.65-2.68 (m, 2H), 3.84 (s, 3H), 7.83 (d, J = 8.0 Hz, 2H), 7.98 (d, J= 8.0 Hz, 2H), 12.75 (s, 1H)

Step III: methyl 4-spiro[l,4,5,6-tetrahydroindazole-7,l'-cyclopentane]-3-ylbenzoate

Title compound was synthesized as described for the synthesis of INT-2-III (methyl 4-(6,6- dimethyl-4-oxo-5,7-dihydro-lH-indazol-3-yl)benzoate)LCMS: m/z 311.1 (M+l)⁺

Step IV: methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H- indazole-7,l'-cyclopentane]-3-yl]benzoate

Title compound was synthesized as described for the synthesis of B-l (methyl 4-[l-(2,6- dichlorobenzoyl)-6,6-dimethyl-4-oxo-5,7-dihydroindazol-3-yl]benzoate). LCMS: m/z 517.0 (M+l)⁺. 'H NMR (DMSO-^, 400 MHz) δ 1.53-1.58 (m, 6H), 1.66-1.69 (m, 6H), 2.45-2.51 (m, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.77 (t, J = 7.6 Hz, 1H), 7.87 (t, J = 7.6 Hz, 1H), 7.96 (t, J = 7.6 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H)

Step IV: Synthesis J-1: 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H- indazole-7,l'-cyclopentane]-3-yl]benzoic acid Title compound was synthesized as described for the synthesis of A-2 (2,6-dichlorophenyl)-(3-iodo-4,5,6,7-tetrahydroindazol-l- yl)methanone. LCMS: m/z 503 (M+l)⁺. ^!H NMR (DMSO-tfe 400 MHz) δ 1.51-1.55 (m, 6H), 1.67-1.69 (m, 6H), 2.46-2.51 (m, 2H), 7.60 (d, J = 8.4Hz, 2H), 7.77 (t, J = 8.0Hz, 1H), 7.88 (d, J= 7.6Hz, 1H), 7.95(d, J= 7.6Hz, 7H), 8.03 (d, J = 8.4Hz, 2H), 13.01 (s, 1H) Synthesis K-2: 4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-

3-yl] benzoic acid

INT-1 - K-1 K-2

Step I: Synthesis K-l: methyl 4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7- tetrahydroindazol-3-yl]-3-fluoro-benzoate

Tetrakis(triphenylphospbine) palladium (0.19 g, 0.17 mmoi) was added to a degassed solution of (2,6-dichlorophenyl)-(3-iodo-4,5,6,7-tetrahydroindazol-l-yl)methanone INT-1- III (0.7 g, 1.6 mmol), (2-fluoro-4-methoxycarbonyl-phenyl)boronic acid (0.35 g, 1.8 mmol) and potassium carbonate (0.45 g, 3.31 mmol) in 2 ml of water and dioxane (4 mL) under an inert argon atmosphere. The reaction medium was heated at 100 °C for 30 niin in microwave. After completion, water was added and extracted with EtOAc (3 x 15 mL). The organic phase was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified on combifalsh system with a gradient of 10 to 30% ethyl acetate-hexanes to obtain the desired product K-l (0.37 g, 52%). LCMS: m/z 447.7 (M+l)⁺. !H NMR (DMSO-rf_tf, 400 MHz) δ 1.73-1.76 (m, 2H), 1.86-1.90 (m, 2H), 2.43-2.49 (m, 2H), 3.14 (t, J = 6.0 Hz, 2H), 3.88 (s, 3H), 7.59 (d, J = 8.0 Hz, 1H), 7.79-7.83 (m, 1H), 7.85-7.87 (m, 2H), 8.58 (d, J= 5.6 Hz, 1H)

Step II: Synthesis K-2: 4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7- tetrahydroindazol-3-yl]-3-fluoro-benzoic acid A solution of 4-[l-(2,4-dichloropyridine-3- carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoate A-l (0.3 g, 0.6 mmol) in a mixture of THF: EtOH: H₂0 (4:4:2, 10 mL) was added LiOH.H₂0 (0.56 g, 1.33 mmol) and the mixture was stirred for 12 h at room temperature. After completion, the solvent was removed under reduced pressure. The crude product was dissolved in the water and acidified with IN HC1 solution up to pH = 3 and extracted with EtOAc (3 x 15 mL). The organic phase was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified on combifalsh system with a gradient of 10 to 30% ethyl acetate-hexanes to obtain the desired product K-2 (0.11 g, 52 %). LCMS: m/z 433.9 (M+l)⁺. !H NMR (DMSO-^, 400 MHz) δ 1.73-1.76 (m, 2H), 1.87-1.90 (m, 2H), 2.45-2.49 (m, 2H), 3.12-3.15 (m, 2H), 7.56 (t, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.82-7.85 (m, 2H), 8.56 (d, J= 5.2 Hz, 1H), 13.41 (s, 1H)

Following intermediates were synthesized from their corresponding starting materials following similar sequence of procedures as for the preparation of A-2 from INT-1-III

No Structure/IUPAC name Characterization INT used

K-3 COOMe LCMS: m/z 447.5 (M+l)⁺. ¾ NMR INT- 1 -XI

(DMSO-t/,5, 400 MHz) δ 1.66-1.77 (m,

4H), 2.33-2.36 (m, 2H), 2.60-2.67 (m,

2H), 3.91 (s, 3H), 7.45 (t, J = 7.2 Hz,

1H), 7.85 (d, J = 10.4 Hz, 1H), 7.91

(d, J= 8.0 Hz, 1H), 8.84 (bs, 2H)

CI methyl 4-[ 1-(3,5- dichloropyridine-4- carbonyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

K-4 COOH LCMS: m/z 433.9 (M+l)⁺. ¾ NMR INT- 1 -XI

(DMSO-t/,5, 400 MHz) δ 1.66-1.77 (m,

4H), 2.33-2.36 (m, 2H), 2.60-2.67 (m,

2H), 7.71 (t, J = 7.6 Hz, 1H), 7.79- 7.82 (m, 1H), 7.88-7.90 (m, 1H), 8.84

»¾ « (bs, 2H), 13.41 (s, 1H)

CI

4- [ 1 -(3 , 5 -dichloropyridine-

4-carbonyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

K-5 COOH LCMS: m/z 394.2 (M+l)⁺. ¾ NMR INT- 1 -XII

(OMSO-d₆, 400 MHz) δ 1.72-1.76 (m,

2H), 1.85-1.89 (m, 2H), 2.17 (s, 3H),

2.32 (s, 3H), 2.42-2.48 (m, 2H), 3.15-

3.20 (m, 2H), 7.21 (d, J= 5.2 Hz, 1H),

7.54 (t, J= 7.6 Hz, 1H), Ί.Ί2-Ί.Ί5 (m,

1H), 7.78-7.81 (m, 1H), 8.42 (d, J =

4-[l-(2,4- 5.6 Hz, 1H), 13.60 (bs, 1H)

dimethylpyridine -3 - carbonyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid K-6 COOH LCMS: m/z 414.1 (M+l)⁺. ¾ NMR INT- 1- DMSO-d₆, 400 MHz) δ 1.72-1.75 (m, XIII

2H), 1.86-1.88 (m, 2H), 2.27 (s, 3H),

2.40-2.45 (m, 2H), 3.13-3.21 (m, 2H),

7.47 (d, J= 4.8 Hz, 1H), 7.56 (t, J =

7.2 Hz, 1H), 7.74-7.77 (m, 1H), 7.81- 7.83 (m, 1H), 8.42 (d, J= 5.6 Hz, 1H),

4- [ 1 -(2-chloro-4-methyl- 13.60 (bs, 1H)

pyridine-3-carbonyl)-

4,5,6,7-tetrahydroindazol-

3-yl]-3-fluoro-benzoic acid

K-7 LCMS: m/z 414.1 (M+l)⁺. ¾ NMR INT- 1-

(DMSO-t/,5, 400 MHz) δ 1.31 (t, J = XIII

6.8 Hz, 3H), 1.74-1.75 (m, 2H), 1.87-

1.89 (m, 2H), 2.27 (s, 3H), 2.48-2.52

(m, 2H), 3.12-3.17 (m, 2H), 4.37 (q, J

= 6.8 Hz, 2H), 7.47 (d, J= 4.8 Hz,

1H), 7.56 (t, J= 8.0 Hz, 1H), 7.77- ethyl 4-[l-(2-chloro-4- 7.80 (m, 1H), 7.83-7.85 (m, lH), 8.41 methyl-pyridine-3 - (d, J= 4.8 Hz, 1H)

carbonyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoate

Κ-8 LCMS: m/z 414.1 (M+l)⁺. ¾ NMR INT-1-

(DMSO-t/,5, 400 MHz) δ 1.73-1.76 (m, XIV

2H), 1.87-1.91 (m, 2H), 2.42-2.49 (m,

2H), 3.11-3.13 (m, 2H), 7.52 (t, J =

7.2 Hz, 1H), 7.74-7.77 (m, 1H), 8.08

(d, J= 5.2 Hz, 1H), 8.80-8.83 (m, lH),

8.89 (d, J= 5.2 Hz, 1H), 13.40 (bs,

4-[l-[2-chloro-4- 1H)

(trifluoromethyl)pyridine-

3 -carbonyl] -4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

K-9 COOH LCMS: m/z 414.1 (M+l)⁺. ¾ NMR INT-1-

(DMSO-^, 400 MHz) δ 1.73-1.76 (m, XIV

2H), 1.86-1.89 (m, 2H), 2.45 (s, 6H),

2.49-2.51 (m, 2H), 3.17 (t, J = 5.2 Hz,

2H), 7.59 (t, J= 7.2 Hz, 1H), 7.74- ) 7.77 (m, 1H), 7.8-7.83 (m, 1H), 9.03

(s, 1H), 13.40 (bs, 1H)

4-[l-(4,6- dichloropyrimidine -5 - carbonyl)-4,5,6,7- tetrahydroindazol-3 -yl] -3 - fluoro-benzoic acid

K-10 LCMS: m/z 415.8 (M+l)⁺. ¾ NMR INT- 1 -XV

(DMSO-t/,5, 400 MHz) δ 1.77-1.80 (m,

2H), 1.85-1.89 (m, 2H), 2.73 (t, J =

5.6 Hz, 2H), 3.13 (t, J= 5.6 Hz, 2H),

7.69 (d, J= 8.8 Hz, 2H), 7.87 (d, J =

5.6 Hz, 1H), 7.99 (d, J= 8.8 Hz, 2H),

8.61 (d, J= 5.6 Hz, 1H), 13.01 (bs,

4- [ 1 -(2,4-dichloropyridine- 1H)

3-carbonyl)-4,5,6,7- tetrahydroindazol-3 - yl]benzoic acid

LCMS: m/z 444.2 (M+l)⁺. ¾ NMR INT- 1 -XV

K-l l (DMSO-t/,5, 400 MHz) δ 1.32 (t, J =

6.4 Hz, 2H), 1.78-1.81 (m, 2H), 1.87-

1.89 (m, 2H), 2.73 (t, J = 6.0 Hz, 2H),

3.13 (t, J= 6.0 Hz, 2H), 4.31 (q, J =

6.4 Hz, 1H), 7.72 (d, J= 8.4 Hz, 2H),

7.87 (d, J= 5.6 Hz, 1H), 8.01 (d, J = methyl 4-[l-(2,4- 8.4 Hz, 2H), 8.61 (d, J= 5.6 Hz, 1H) ' dichloropyridine -3 - carbonyl)-4,5,6,7- tetrahydroindazol-3 - yl]benzoate

The list of examples below, but not limited to these, can also be synthesized following general synthesis described above:

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydrooxepino[2,3-c]pyrazol- l-yl]benzoic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydrooxepino[2,3-c]pyrazol-l-yl]benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydrooxepino[2,3-c]pyrazol-l- yl] benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydrooxepino[2,3-c]pyrazol-l-yl]benzoic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydro-4H-oxocino[2,3- c]pyrazol- 1 -yl]pyridine-3 -carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-5,6,7,8-tetrahydro-4H-oxocino[2,3-c]pyrazol-l- yl] benzoic acid;

4- [3-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6,7,8-tetrahydro-4H-oxocino[2,3-c]pyrazol-l- yl] benzoic acid;

5- [3-(2-chloro-6-methyl-benzoyl)-5,6,7,8-tetrahydro-4H-oxocino[2,3-c]pyrazol-l- yl] pyridine -2-carboxylic acid;

4- [3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol- l-yl]benzoic acid;

5- [3-(2,6-dichlorophenyl)sulfonyl-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol-l- yl] pyridine -2-carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol- l-yl]benzoic acid; 4-[3-(2-chloro-6-methyl-benzoyl)-8,8-difluoro-4,5,6,7-tetrahydrocyclohepta[c]pyrazol-l- yl] benzoic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]spiro[5,6,7,8-tetrahydro-4H- cycloocta[c]pyrazole-9, l'-cyclopropane]-l-yl]pyridine-3-carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonylspiro[5,6,7,8-tetrahydro-4H-cycloocta[c]pyrazole-9,r- cyclopropane] -l-yl]benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6,7,8-tetrahydro-4H- cycloocta[c]pyrazole-9, l'-cyclopropane]-l-yl]benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6,7,8-tetrahydro-4H-cycloocta[c]pyrazole-9,r- cyclopropane]-l-yl]benzoic acid;

6-[3-[[2-chloro-6-(trifluorome1hyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l-yl]pyridine-

3- carboxylic acid;

6-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]pyridine-3-carboxylic acid;

6-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]pyridine-3- carboxylic acid;

6-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]pyridine-3-carboxylic acid;

2-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl]pyrimidine-5-carboxylic acid;

2-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]pyrimidine-5-carboxylic acid;

2-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]pyrimidine-5- carboxylic acid;

2-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]pyrimidine-5-carboxylic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydro-4H- cyclohepta[c]pyrazol-l-yl]pyridine-3-carboxylic acid;

4- [3-(2,6-dichlorophenyl)sulfonyl-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol-l-yl]benzoic acid; 4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol-l- yl] benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol-l-yl]benzoic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7,8,9- hexahydrocycloocta[c]pyrazol-l-yl]pyridine-3-carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5, 6,7,8, 9-hexahydrocycloocta[c]pyrazol-l-yl]benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5, 6,7,8, 9-hexahydrocycloocta[c]pyrazol-l- yl] benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7,8,9-hexahydrocycloocta[c]pyrazol-l-yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3- yl] benzene sulfonamide ;

[4-[ 1 -(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]phenyl] -( 1 - piperidyl)methanone;

[4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]phenyl]- pyrrolidin- 1 -yl-methanone;

azetidin- 1 -yl-[4-[ 1 -(2 -chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3- yl] phenyl] methanone ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]Benzamide;

(2-chloro-6-methyl-phenyl)-[3-[4-( 1 -piperidylsulfonyl)phenyl] -4,5,6,7-tetrahydroindol- 1 - yl] methanone;

[2-chloro-6-(trifluoromethyl)phenyl]-[3-(4-pyrrolidin-l-ylsulfonylphenyl)-4,5,6,7- tetrahydroindol- 1 -yl]methanone ;

[3-[4-(azetidin- 1 -ylsulfonyl)phenyl] -4,5,6,7-tetrahydroindol- 1 -yl] -(2-chloro-6-methyl- phenyl)methanone ; [4-[3 -(2-chloro-6-methyl-benzoyl)-4,5 ,6,7-tetrahydroindol- 1 -yl]phenyl] -(1, 1 -dioxo- 1 ,4- thiazinan-4-yl)methanone ;

[4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]phenyl]-(l- piperidyl)methanone;

(2-chloro-6-methyl-phenyl)-[l-(4-moφholinosulfonylphenyl)-4,5,6,7-tetrahydroindol-3- yl]methanone;

[4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7 etrahydroindol-l-yl]phenyl]-pyrrolidin- 1-yl-methanone;

azetidin- 1 -yl-[4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol- 1 - yl] phenyl] methanone ;

[4-[3 -(2 -chloro-6-methyl-benzoyl)-4,5 ,6,7-tetrahydroindol- 1 -yl]phenyl] -(1, 1 -dioxo- 1 ,4- thiazinan-4-yl)methanone ;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l-yl]Benzamide;

(2-chloro-6-methyl-phenyl)-[ 1 -[4-( 1 -piperidylsulfonyl)phenyl] -4,5,6,7-tetrahydroindol-3- yl] methanone;

[2-chloro-6-(trifluoromethyl)phenyl]-[l-(4-pyrrolidin-l-ylsulfonylphenyl)-4,5,6,7- tetrahydroindol-3 -yl]methanone ;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l- yl] benzene sulfonamide ;

[ 1 -[4-(azetidin- 1 -ylsulfonyl)phenyl] -4,5,6,7-tetrahydroindol-3-yl] -(2-chloro-6-methyl- phenyl)methanone ;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-5-(3-hydroxyazetidine-l-carbonyl)- 4,5 ,6,7-tetrahydroindol- 1 -yl]benzoic acid;

4-[5-(azetidine-l-carbonyl)-3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindol- 1 -yl]benzoic acid;

l-(4-carboxyphenyl)-3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-2,3,4,5,6,7- hexahydroindole-5 -carboxylic acid;

l-(4-carboxyphenyl)-3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindole-5 -carboxylic acid; 4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-5-(3-hydroxyazetidine-l-carbonyl)- 4,5 ,6,7-tetrahydroindol- 1 -yl]benzoic acid;

4-[5-(azetidine-l-carbonyl)-3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindol- 1 -yl]benzoic acid;

l-(4-carboxyphenyl)-3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindole-5 -carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-5-(3-hydroxyazetidine-l-carbonyl)-4,5,6,7- tetrahydroindol- 1 -yl]benzoic acid;

4-[5-(azetidine-l-carbonyl)-3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol- l-yl]benzoic acid;

l-(4-carboxyphenyl)-3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindole-5- carboxylic acid;

(2-chloro-6-methyl-phenyl)-[l-(p-tolyl)-4,5,6,7-tetrahydroindol-3-yl]methanone;

[2-chloro-6-(trifluorome1hyl)phenyl]-[l-(p olyl)-4,5,6j etrahydroindol-3-yl]methanone 3-(2,6-dichlorophenyl)sulfonyl-l-(p-tolyl)-4,5,6,7-tetrahydroindole;

3-[[2-chloro-6-(trifluorome1hyl)phenyl]methyl]-l-(p olyl)-4,5,6,7 etrahydroindole;

3- (2,6-dichlorophenyl)sulfonyl-l-(p-tolyl)-4,5,6,7-tetrahydroindole;

[2-chloro-6-(trifluorome1hyl)phenyl]-[l-(p olyl)-4,5,6j etrahydroindol-3-yl]methanone

4- [l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-6-(3-hydroxyazetidine-l-carbonyl)- 4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

4-[6-(azetidine-l-carbonyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindazol-3-yl]benzoic acid;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindazole-6-carboxylic acid; 3- (4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindazole-6-carboxylic acid;

4- [l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-6-(3-hydroxyazetidine-l-carbonyl)- 4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

4-[6-(azetidine-l-carbonyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindazol-3-yl]benzoic acid;

3-(4-carboxyphenyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindazole-6-carboxylic acid;

3- (4-carboxyphenyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindazole-6-carboxylic acid;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-6-(3-hydroxyazetidine-l-carbonyl)-4,5,6,7- tetrahydroindazol-3-yl]benzoic acid;

4-[6-(azetidine- 1 -carbonyl)- 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -4,5,6,7- tetrahydroindazol-3-yl]benzoic acid;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazole-6- carboxylic acid;

(2-chloro-6-methyl-phenyl)-[3-(p-tolyl)-4,5,6,7-tetrahydroindazol-l-yl]methanone;

[2-chloro-6-(trifluorome1hyl)phenyl]-[3-(p-tolyl)-4,5,6,7-tetrahydroindazol-l-yl]methanone; l-(2,6-dichlorophenyl)sulfonyl-3-(p-tolyl)-4,5,6,7-tetrahydroindazole;

l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-3-(p-tolyl)-4,5,6,7-tetrahydroindazole; l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-3-(p-tolyl)-4,5,6,7-tetrahydroindole;

l-(2,6-dichlorophenyl)sulfonyl-3-(p-tolyl)-4,5,6,7-tetrahydroindole;

[2-chloro-6-(trifluorome1hyl)phenyl]-[3-(p-tolyl)-4,5,6,7-tetrahydroindol-l-yl]methanone;

(2-chloro-6-methyl-phenyl)-[3-(p-tolyl)-4,5,6,7-tetrahydroindol-l-yl]methanone;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindole-6- carboxylic acid; 3- (4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindole-6- carboxylic acid;

4- [6-(azetidine- 1 -carbonyl)- 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -4,5,6,7-tetrahydroindol-

3- yl]benzoic acid;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-6-(3-hydroxyazetidine-l-carbonyl)-4,5,6,7- tetrahydroindol-3-yl]benzoic acid;

3-(4-carboxyphenyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindole-6-carboxylic acid;

3- (4-carboxyphenyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindole-6-carboxylic acid;

4- [6-(azetidine-l-carbonyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindol-3-yl]benzoic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-6-(3-hydroxyazetidine-l-carbonyl)- 4,5,6,7-tetrahydroindol-3-yl]benzoic acid;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindole-6-carboxylic acid;

3- (4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindole-6-carboxylic acid;

4- [6-(azetidine-l-carbonyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindol-3-yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-6-(3-hydroxyazetidine-l-carbonyl)- 4,5,6,7-tetrahydroindol-3-yl]benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]-2-hydroxy- cyclohexanecarboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]-2 -hydroxy- cyclohexanecarboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-2-hydroxy- cyclohexanecarboxylic acid; 4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l-yl]-2- hydroxy-cyclohexanecarboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]cyclohexene-l-carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]cyclohexene-l- carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]cyclohexene-l-carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl] cyclohexene- 1 -carboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]cyclohexanecarboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l- yl]cyclohexanecarboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]cyclohexanecarboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl]cyclohexanecarboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]cyclohex-3-ene-l- carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]cyclohex-3-ene-l- carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]cyclohex-3-ene-l- carboxylic acid;

4-[3-[[2-chloro-6-(trifluorome1hyl)phenyl]methyl]-4,5,6,7 etrahydroindazol-l-yl]cyclohex-

3 - ene-1 -carboxylic acid;

4- [3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]cyclohexanecarboxylic acid; 4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l- yl]cyclohexanecarboxylic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3- yl]cyclohexanecarboxylic acid;

4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]cyclohexanecarboxylic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3- yl]cyclohexanecarboxylic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]cyclohexanecarboxylic acid;

4-[l-[[2-chloro-6-(trifluorome1hyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-

3- ene-l-carboxylic acid;

4- [l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3-ene-l- carboxylic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3-ene-l- carboxylic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3-ene-l- carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3- yl]piperidine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]piperidine-4-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]piperidine-4- carboxylic acid; l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]piperidine-4- carboxylic acid;

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]piperidine-4-carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]-3,6- dihydro-2H-pyridine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6j etrahydroindazol-3-yl]-3,6-dihydro-2H-pyridine- 4-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3,6-dihydro-2H- pyridine -4-carboxylic acid

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3,6-dihydro-2H-pyridine- 4-carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- hydroxy-piperidine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6J-tetrahydroindazol-3-yl]-3-hydroxy-piperidine-4- carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-hydroxy- piperidine-4-carboxylic acid;

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-hydroxy-piperidine-4- carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7 etrahydroindol-3-yl]-3-hydroxy- piperidine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6J-tetrahydroindol-3-yl]-3-hydroxy-piperidine-4- carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]-3-hydroxy- piperidine-4-carboxylic acid;

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]-3-hydroxy-piperidine-4- carboxylic acid; l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]-3,6-dihydro-2H-pyridine-4- carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]-3,6-dihydro-2H- pyridine -4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6j etrahydroindol-3-yl]-3,6-dihydro-2H-pyridine-4- carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]-3,6- dihydro-2H-pyridine-4-carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7 etrahydroindol-3-yl]piperidine-4- carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]piperidine-4-carboxylic acid; l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]piperidine-4- carboxylic acid;

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]piperidine-4-carboxylic acid

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3- ene-1 -carboxylic acid;

4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3-ene-l-carboxylic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3-ene-l- carboxylic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3-ene-l-carboxylic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3- yl]cyclohexanecarboxylic acid;

4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]cyclohexanecarboxylic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3- yl]cyclohexanecarboxylic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]cyclohexanecarboxylic acid; 4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid;

4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3-fluoro- benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindol-3-yl]benzoic acid; methane;

4-[l-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3-fluoro-benzoic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindol-l-yl]benzoic acid;

4-[3-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro-benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]-hydroxy-methyl]-4,5,6,7-tetrahydroindol-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-N-methyl-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid; 4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfanyl-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenoxy]-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]benzoic acid;

4-[3-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-N-methyl-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]-hydroxy-methyl]-4,5,6,7-tetrahydroindazol-l-yl]-

3- fluoro-benzoic acid;

4- [3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfanyl-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenoxy]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,5a,6,6a-tetrahydro-4H-cyclopropa[e]indol-3- yl] -3-fluoro-benzoic acid; 4-[3-(2,6-dichlorobenzoyl)-4,5,5a,6,7,7a-hexahydrocyclobuta[g]indol-l-yl]-3-fluoro-benzoic acid;

4-[3-(2,6-dichlorobenzoyl)-4a,5,5a,6-tetrahydro-4H-cyclopropa[f]indol-l-yl]-3-fluoro- benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-5,5a,6,6a-tetrahydro-4H-cyclopropa[g]indol-l-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,5a,6,6a-tetrahydro-4H-cyclopropa[e]indazol-3- yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)spiro[6,7-dihydro-5H-indole-4,l'-cyclopropane]-3-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[6,7-dihydro-5H-indole-4,r-cyclopropane]-

3 - yl] -3 -fluoro-benzoic acid;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-6,7-dihydro-5H-pyrano[3,2-b]pyrrol-3-yl]-3- fluoro-benzoic acid;

4-[l-(2,6-dichlorobenzoyl)-6,7-dihydro-5H-pyrano[3,2-c]pyrazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2,6-dichlorobenzoyl)spiro[6,7-dihydro-5H-indazole-4,r-cyclopropane]-3-yl]-3-fluoro- benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-6,7-dihydro-5H-pyrano[3,2-c]pyrazol-3-yl]-3-fluoro- benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,4-difluoro-6,7-dihydro-5H-indazol-3-yl]-3-fluoro- benzoic acid;

4-[l-(2,6-dichlorobenzoyl)-4,4-difluoro-6,7-dihydro-5H-indazol-3-yl]-3-fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrazolo[4,3-b]pyridin-3-yl]-3- fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)spiro[6,7-dihydro-5H-indazole-4,r-cyclopropane]-3-yl]-3- fluoro-benzoic acid; 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[6,7-dihydro-5H-indazole-4,r- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-6,7-dihydro-5H-pyrano[3,2-c]pyrazol-3-yl]-3- fluoro-benzoic acid;

4-[l-(2,6-dichlorobenzoyl)-6,7-dihydro-5H-pyrano[3,2-b]pyrrol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2,6-dichlorobenzoyl)spiro[6,7-dihydro-5H-indole-4,l'-cyclopropane]-3-yl]-3-fluoro- benzoic acid;

4-[l-(2,6-dichlorobenzoyl)-4,4-difluoro-6,7-dihydro-5H-indol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,4-difluoro-6,7-dihydro-5H-indol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-6,7-dihydro-5H-pyrano[3,2-b]pyrrol-3-yl]-3-fluoro- benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6-dihydro-4H-indazole-7,l'-cyclopropane]-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H-indazole-7,r- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6-dihydro-4H-pyrano[2,3-c]pyrazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrazolo[3,4-b]pyridin-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-5,6-dihydro-4H-pyrano[2,3-c]pyrazol-l-yl]-3-fluoro- benzoic acid;

4-[3-(2,6-dichlorobenzoyl)-5,6-dihydro-4H-pyrano[2,3-c]pyrazol-l-yl]-3-fluoro-benzoic acid;

4-[3-(2,6-dichlorobenzoyl)spiro[5,6-dihydro-4H-indazole-7,l'-cyclopropane]-l-yl]-3-fluoro- benzoic acid;

4-[3-(2,6-dichlorobenzoyl)-7,7-difluoro-5,6-dihydro-4H-indazol-l-yl]-3-fluoro-benzoic acid; 4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6-dihydro-4H-indole-7,l'-cyclopropane]-l-yl]-3- fluoro-benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6-dihydro-4H-indole-7,l'-cyclopropane]-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H-indole-7,r-cyclopropane]- 1-yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrrolo[2,3-b]pyridin-l-yl]-3- fluoro-benzoic acid;

4-[5-(2-chloro-6-methyl-benzoyl)-3,4-dihydro-2H-pyrano[2,3-b]pyrrol-7-yl]-3-fluoro- benzoic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-l-yl]cyclohexanecarboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l- yl]cyclohexanecarboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]cyclohexanecarboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-l-yl]cyclohex-3- ene-l-carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-l-yl]cyclohex-3-ene-l-carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l-yl]cyclohex-3-ene-l- carboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]cyclohex-3-ene-l-carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-l- yl]cyclohexanecarboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]cyclohexanecarboxylic acid; 4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-l- yl] cyclohexene- 1 -carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-l-yl]cyclohexene-l-carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl] -4,5,6,7-tetrahydroindol- 1 -yl] cyclohexene- 1 - carboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]cyclohexene-l-carboxylic acid;

4-[3-[[2-chloro-6-(trifluorome1hyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l-yl]-2- hydroxy-cyclohexanecarboxylic acid

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-2-hydroxy- cyclohexanecarboxylic acid

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]-2 -hydroxy- cyclohexanecarboxylic acid

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-l-yl]-2-hydroxy- cyclohexanecarboxylic acid

4-[3-[l-[2-chloro-6-(trifluoromethyl)phenyl]cyclopropyl]-4,5,6,7-tetrahydroindazol-l- yl] benzoic acid

4-[3-[[2-chloro-6-(trifluorome1hyl)phenyl]-difluoro-methyl]-4,5,6,7-tetrahydroindazol-l- yl] benzoic acid

4-[3-[l-(2-chloro-6-methyl-phenyl)cyclopentyl]-4,5,6,7-tetrahydroindazol-l-yl]benzoic acid

4-[l-[l-[2-chloro-6-(trifluoromethyl)phenyl]cyclopropyl]-4,5,6,7-tetrahydroindol-3- yl] benzoic acid

4-[l-[l-[2-chloro-6-(trifluoromethyl)phenyl]cyclobutyl]-4,5,6,7-tetrahydroindazol-3- yl] benzoic acid;

4-[l-[4-(2-chloro-6-methyl-phenyl)tetrahydropyran-4-yl]-4,5,6,7-tetrahydroindol-3- yl] benzoic acid;

4-[5-(2-chloro-6-methylbenzoyl)-3,4-diazatricyclo[5.2.1.0^A{2,6}]deca-2(6),4-dien-3-yl]-3- fluorobenzoic acid; 4-{5-[2-chloro-6-(trifluoromethyl)benzoyl]-3,4-diazatricyclo[5.2.2.0^A{2,6}]undeca-2(6),4- dien-3- yl}-3-fluorobenzoic acid;

4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]-4, 5-diazatricyclo[6.2.1.0^A{2,6}]undeca-2(6),3- dien-5- yl}-3-fluorobenzoic acid;

4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]-4, 5-diazatricyclo[6.1.1.0^A{2,6}]deca-2(6),3- dien-5-yl}-3- fluorobenzoic acid;

4-{ l-[2-chloro-6-(trifluoromethyl)benzoyl]-3H,4H,5H,5aH,6H,6aH-cyclopropa[e]indazol-3- yl} -3 -fluorobenzoic acid;

4-[5-(2,6-dichlorobenzoyl)-3, 4-diazatricyclo[6.2.1.0^A{2,6}]undeca-2(6),4-dien-3-yl]-3- fluorobenzoic acid;

4-[3-(2,6-dichlorobenzoyl)-lH,4H,5H,5aH,6H,7H,7aH-cyclobuta[g]indazol-l-yl]-3- fluorobenzoic acid ;

4-[3-(2,6-dichlorobenzoyl)-lH,4H,5H,5aH,6H,7H,7aH-cyclobuta[g]indol-l-yl]-3- fluorobenzoic acid;

4-[5-(2,6-dichlorobenzoyl)-3-azatricyclo[6.2.1.0^A{2,6}]undeca-2(6),4-dien-3-yl]-3- fluorobenzoic acid;

4-[3-(2-chloro-6-methylbenzoyl)-3-azatricyclo[5.2.1.0^A{2,6}]deca-2(6),4-dien-5-yl]-3- fluorobenzoic acid;

4- {3-[2-chloro-6-(trifluoromethyl)benzoyl]-3-azatricyclo[5.2.2.0^A{2,6}]undeca-2(6),4-dien-

5- yl}-3- fluorobenzoic acid;

4-[5-(2,6-dichlorobenzoyl)-4,5-diazatricyclo[6.2.1.0^A{2,6}]undeca-2(6),3-dien-3-yl]-3- fluorobenzoic acid and

4-[3 -(2-chloro-6-methylbenzoyl)-3 , 4-diazatricyclo [5.2.1.0^A{2,6 } ] deca-2(6),4-dien-5 -yl] -3 - fluorobenzoic acid

6- [l-[4-(4-chloro-2-methyl-3-pyridyl)tetrahydropyran-4-yl]-4,5,6,7-tetrahydroindol-3- yl] pyridine -3 -carboxylic acid;

4-[l-[l-[4-chloro-2-(trifluoromethyl)-3-pyridyl]cyclopropyl]-4,5,6,7-tetrahydroindol-3- yl] benzoic acid; 6-[l-[l-[4-chloro-2-(trifluoromethyl)-3-pyridyl]cyclobutyl]-4,5,6,7-tetrahydroindazol-3- yl] pyridine -3 -carboxylic acid;

6-[3-[[2-chloro-4-(trifluorome1hyl)-3-pyridyl]me1hyl]-5,6,7,8 etrahydro-4H-oxocino[2,3- c]pyrazol- 1 -yl]pyridine-3 -carboxylic acid;

5- [3-[(2,4-dichloro-3-pyridyl)sulfonyl]-8,8-difluoro-4,5,6,7 etrahydrocyclohepta[c]pyrazol- 1-yl] pyridine -2 -carboxylic acid;

6- [3-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindazol-l- yl] pyridine -3 -carboxylic acid;

6-[3-[[4-chloro-2-(trifluorome1hyl)-3-pyridyl]me1hyl]-4,5,6J-tetrahydroindazol-l- yl] pyridine -3 -carboxylic acid;

4-[l-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-3- yl] benzene sulfonamide ;

(4-chloro-2-methyl-3-pyridyl)-[3-[4-(l-piperidylsulfonyl)phenyl]-4,5,6,7-tetrahydroindol-l- yl]methanone;

4- [3-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-l- yl] benzene sulfonamide ;

l-(4-carboxyphenyl)-3-[[4-chloro-2-(trifluorome1hyl)-3-pyridyl]sulfonyl]-4,5,6,7- tetrahydroindole-5 -carboxylic acid;

l-(4-carboxyphenyl)-3-[[4-chloro-2-(trifluorome1hyl)-3-pyridyl]methyl]-4,5,6,7- tetrahydroindole-5 -carboxylic acid;

5- [l-[[4-chloro-2-(trifluoromemyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3- yl] bicyclo [2.2.2] octane -2-carboxylic acid;

5-[l-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-3- yl] bicyclo [2.2.2] octane -2-carboxylic acid;

5-[l-(4-chloro-2-methyl-pyridine-3-carbonyl)-4,5,6,7-tetrahydroindol-3- yl] bicyclo [2.2.2] octane -2-carboxylic acid;

l-[l-[[4-chloro-2-(trifluoromemyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]-3,6- dihydro-2H-pyridine-4-carboxylic acid; l-[l-[[2-chloro-6-(trifluorome1hyl)phenyl]methyl]-4,5,6,7 etrahydroindol-3-yl]piperidine-4- carboxylic acid;

4-[l-[[4-chloro-2-(trifluorome1hyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3- yl]cyclohexanecarboxylic acid;

4-[l-[[4-chloro-2-(trifluorome1hyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3- yl] cyclohex-3 -ene- 1 -carboxylic acid;

4-[l-[3-chloro-5-(trifluoromethyl)pyridazin-4-yl]sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

4-[l-[4-chloro-6-(trifluoromethyl)pyrimidin-5-yl]sulfonyl-4,5,6,7-tetrahydroindazol-3- yl] benzoic acid;

4-[l-[(2,4-dichloro-3-pyridyl)sulfonyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-[[2-chloro-4-(trifluorome1hyl)-3-pyridyl]me1hyl]-4,5,6j etrahydroindazol-3-yl]-3- fluoro-benzoic acid;

4-[3-[[2-chloro-4-(trifluoromethyl)-3-pyridyl]sulfonyl]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[[2-chloro-4-(trifluorome1hyl)-3-pyridyl]me1hyl]-4,5,6j etrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[[2-chloro-4-(trifluoromethyl)-3-pyridyl]oxy]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[[3-chloro-5-(trifluoromethyl)-4-pyridyl]amino]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[[2-chloro-4-(trifluoromethyl)-3-pyridyl]sulfanyl]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)-5,5a,6,6a-tetrahydro-4H-cyclopropa[g]indol- l-yl]-3-fluoro-benzoic acid; 4-[3-(2,4-dichloropyridine-3-carbonyl)-4a,5,5a,6-tetrahydro-4H-cyclopropa[f]indol-l-yl]-3- fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)-4,5,5a,6,7,7a-hexahydrocyclobuta[g]indol-l-yl]-3- fluoro-benzoic acid;

4-[l-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-3-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydropyrrolo[3,2- b]pyridin-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-4-methyl-pyridine-3-carbonyl)spiro[6,7-dihydro-5H-indole-4,r- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[6,7-dihydro-5H-indole-4,r- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-6,7-dihydro-5H-pyrano[3,2-b]pyrrol-

3 - yl] -3 -fluoro-benzoic acid;

4- [l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[6,7-dihydro-5H-indazole-4,r- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-(2,4-dichloropyridine-3-carbonyl)spiro[6,7-dihydro-5H-indazole-4,l'-cyclopropane]-3- yl] -3 -fluoro-benzoic acid;

4-[l-(2-chloro-4-methyl-pyridine-3-carbonyl)-6,7-dihydro-5H-pyrano[3,2-c]pyrazol-3-yl]-3- fluoro-benzoic acid;

4-[l-(2,4-dichloropyridine-3-carbonyl)-4,4-difluoro-6J-dihydro-5H-indazol-3-yl]-3-fluoro- benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydropyrazolo[4,3- b]pyridin-3-yl]-3-fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)spiro[5,6-dihydro-4H-indazole-7,r- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[5,6-dihydro-4H-indazole-7,r- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid; 4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-5,6-dihydro-4H-pyrano[2,3- c]pyrazol- 1 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydropyrazolo[3,4- b] pyridin- 1 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3 -(2-chloro-4-methyl-pyridine-3 -carbonyl)-5 ,6-dihydro-4H-pyrano [2,3 -c]pyrazol- 1 -yl] -3 - fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)-7 -difluoro-5,6-dihydro-4H-indazol-l-yl]-3- fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)-7,7-difluoro-5,6-dihydro-4H-indazol-l-yl]-3-fluoro- benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)spiro[5,6-dihydro-4H-indazole-7,l'-cyclopropane]-l- yl] -3 -fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)-5,6-dihydro-4H-pyrano[2,3-c]pyrazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[5,6-dihydro-4H-indole-7,r- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)spiro[5,6-dihydro-4H-indole-7,r- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[5-(2-chloro-4-methyl-pyridine-3-carbonyl)-3,4-dihydro-2H-pyrano[2,3-b]pyrrol-7-yl]-3- fluoro-benzoic acid;

4-[3-(4-chloro-2-methyl-pyridine-3-carbonyl)-7,7-difluoro-5,6-dihydro-4H-indol-l-yl]-3- fluoro-benzoic acid;

4-[3 -(3 ,5 -dichloropyridine-4-carbonyl)-7,7-difluoro-5 ,6-dihydro-4H-indol- 1 -yl] -3 -fluoro- benzoic acid and

4-[5-(2,4-dichloropyridine-3-carbonyl)-3,4-dihydro-2H-pyrano[2,3-b]pyrrol-7-yl]-3-fluoro- benzoic acid. BIOLOGICAL ACTIVITY

[0101] TR-FRET binding assay protocol:

The binding affinity of the compounds to the ROR gamma ligand binding domain (LBD) was evaluated using a LanthaScreen time-resolved FRET (TR-FRET) assay (LanthaScreen® TR- FRET ROR gamma Coactivator Assay Kit, rabbit, Invitrogen, A15147). Briefly, varying concentrations of NCEs were incubated with fluorescein-D22 coactivator peptide, LanthaScreen™ Tb anti-GST antibody and GST tagged ROR gamma LBD in a 384-well low-volume assay plate (Corning® 384 well plates, low volume, Sigma-aldrich, CLS3677). Each reaction consisted of 150nM fluorescein-D22 coactivator peptide, 2nM Tb anti-GST antibody, 2nM ROR gamma LBD and compounds at desired concentrations diluted with Coregulator Buffer D (proprietary buffer, pH 7.5), where the final assay volume was 20μΙ_^ and concentration of DMSO was adjusted to 1%. Appropriate controls included in the assay, vehicle control was the positive control and negative control was evaluated by incubating the reaction in absence of ROR gamma LBD. The reaction was incubated at room temperature for 1 hour in dark. Upon incubation, the Tb-anti-GST antibody indirectly labels the nuclear receptor by binding to the GST tag. Binding of the antagonist to the ROR gamma LBD causes a conformational change that result in a decrease in the affinity of the ROR gamma for a coactivator peptide. The separation of the fluorescently labeled coactivator peptide from the ROR gamma with the terbium-labeled antibody causes a decrease in the TR-FRET signal. The plate was read in Flexstation 3 in TR-FRET mode with an excitation wavelength of 332nm and emission wavelengths of 490nm and 520nm. Data was analyzed by calculating the TR-FRET ratio by dividing the emission at 520 nm by the emission at 495 nm and determining the IC50 value by fitting the data using an equation for a sigmoidal dose response (varying slope), as provided by GraphPad™ Prism. Vehicle control (DMSO) was normalized to 0% inhibition and DMSO control in the absence of ROR gamma LBD to 100% inhibition.

[0102] RORgt Transactivation Reporter Assay Protocol:

The inhibition of RORgt activity in cells was evaluated using a GAL4-UAS reporter system in HEK293T cells employing a luciferase read out. ROR gamma-t ligand binding domain (LBD) was cloned into the pFN26A(BIND) vector (Promega #E138A) containing yeast GAL4-DBD to form a RORgt LBD-GAL4 DBD fusion construct. This vector also contained a Renilla Luciferase reporter expressed under a SV40 promoter which was used as a control for transfection efficiency. A transcriptional reporter expression construct pGL4.35 (Promega #E137A) was used to monitor RORgt LBD-GAL4 activity. This construct contained nine repeats of GAL4 binding site/upstream activating sequence (UAS) controlling expression of a firefly luciferase reporter Luc2P. When transfected together in cells, the RORg-LBD-DBD fusion protein drives expression of the luciferase reporter.

[0103] For the assay, HEK293T cells were plated in a flat bottom 96 well plate at a density of

25,000 cells/well/ lOOul of DMEM high glucose medium (Sigma D5648) containing 10%FBS and antibiotic. Cells were incubated overnight at 37C/5%C02. The next day, medium from the wells was removed and replaced with 30ul of OptiMEM® (Invitrogen #31985070). lOOng each of pBIND RORg LBD-DBD and pGL4.35 reporter plasmids was transfected in HEK293T cells using Lipofectamine 2000 (Invitrogen #11668-019) where lOul of transfection complex was added to the each well. Control transfections were performed with an empty pFN26A vector and pGL4.35 vector. The transfected cells were incubated for 5 hours at 37C/5%C02. After incubation, 40ul of DMEM high glucose medium without FBS, with antibiotic was added to each well.

[0104] A lOmM stock solution of test compound prepared in 100% DMSO was first diluted in DMSO and then in DMEM medium without FBS to give the required final compound concentration. Concentration of DMSO in the test compound solution was 0.4%. 20ul of diluted compound solution was added to each well. Cells were incubated overnight (18-24 hours) at 37C/5%C02.

[0105] The next day, luciferase assay was performed using the Dual Glo® Luciferase Assay

System (Promega #E2940). Briefly, medium was removed from the wells and replaced with 40ul IX Passive Lysis Buffer (Promega #E1941). Plate was incubated at room temperature on a plate shaker at lOOOrpm for 40min. After incubation, plate was centrifuged at lOOOrpm for 2 min. 20ul of the lysate was transferred from each well to that of solid white half area 96well plate (Costar #3693). Dual Glo® Reagent was thawed to room temperature and 20ul was added to each well containing lysate. Plate was centrifuged at 1000rpm/2min and incubated at room temperature on a plate shaker at 600rpm/25min. Firefly luciferase signal was measured on a Tecan Safire2. After measurement, 20ul of Dual Glo® Stop Glo® Reagent was added to each well. Plate was centrifuged at 1000rpm/2min and incubated at room temperature on a plate shaker at 600rpm/25min. Renilla luciferase signal was measured on Tecan Safire 2. IC5₀ values for test compounds were calculated from the normalized luciferase signal data using GraphPad Prism software.

[0106] Data for representative compounds of the present disclosure are given below in Table

1 : Table 1: TR-FRET binding assay: and Transactivation assay with GAL4-DBD/RORy-LBD: IC50 values:

Example TR-FRET binding Transactivation assay with

No assay IC50 (nM) GAL4-DBD/RORy-LBD IC₅₀

(nM)

A-l >5000 500-5000

A-2 <500 <500

A-3 >5000 <500

A-4 <500 <500

A-5 ND <500

A-6 <500 <500

A-7 ND 500-5000

A-8 <500 <500

A-9 ND >5000

A-10 <500 500-5000

A-l l ND <500

A-12 ND <500

A-13 ND >5000

A-14 <500 <500

A-15 <500 <500

A-16 ND < 500

A-17 <500 <500

A-18 <500 <500

A-19 ND <500

A-20 ND >5000

A-21 ND <500

A-22 ND <500

A-23 ND <500

A-24 ND <500

A-25 ND <500

A-26 ND 500-5000

A-27 ND >5000 A-28 ND <500

A-29 ND <500

A-30 ND <500

A-31 ND <500

A-32 ND 500-5000

A-33 ND <500

A-34 ND <500

A-35 ND 500-5000

A-36 ND 500-5000

A-37 ND <500

A-38 ND <500

A-39 ND <500

A-40 ND <500

A-41 ND <500

A-42 ND <500

A-43 ND <500

A-44 ND <500

A-45 ND <500

A-46 ND <500

A-47 ND <500

A-48 ND <500

A-49 ND <500

A-50 ND <500

A-51 ND <500

A-52 ND <500

A-53 ND >5000

A-54 ND <500

A-55 ND <500

A-56 ND >5000

A-57 ND <500

A-58 ND >5000

A-59 ND <500 A-60 ND <500

A-61 ND <500

A-62 ND <500

A-63 ND <500

A-64 ND <500

A-65 ND <500

A-66 ND <500

A-67 ND <500

A-68 ND <500

A-69 ND <500

A-70 ND <500

A-71 ND >5000

A-72 ND <500

A-73 ND <500

A-74 ND <500

B-l ND >5000

B-2 ND >5000

B-3 ND >5000

B-4 ND >5000

B-5 ND 500-5000

B-6 ND >5000

B-7 ND < 500

B-8 ND <500

B-9 ND >5000

B-10 ND < 500

B-l l ND 500-5000

B-12 ND >5000

B-13 ND >5000

B-14 ND >5000

B-15 ND >5000

B-16 ND <500

B-17 ND <500 C-l ND >5000

C-2 ND < 500

C-3 ND 500-5000

C-4 ND < 500

C-5 ND < 500

C-6 ND <500

C-7 ND >5000

C-8 <500 < 500

C-9 ND 500-5000

C-10 <500 < 500

C-l l ND >5000

C-12 ND 500-5000

D-2 ND >5000

D-3 ND 500-5000

D-4 ND >5000

E-l ND < 500

F-l ND >5000

F-2 ND >5000

F-3 ND >5000

G-l ND 500-5000

G-2 ND <500

G-3 ND <500

G-4 ND <500

H-l ND 500-5000

H-2 ND 500-5000

1-1 ND 500-5000

1-2 ND >5000

1-3 ND <500

J-l ND >5000

K-l ND <500

K-2 ND <500

K-3 ND >5000 K-4 ND >5000

K-5 ND >5000

Κ-6 ND >5000

Κ-7 ND >5000

Κ-8 ND <500

Κ-9 ND <500

Κ-10 ND < 500

Κ-11 ND < 500

"ND - Not Determined"

Although the subject matter has been described in considerable detail with reference to certain preferred embodiments thereof, other embodiments are possible. As such, the spirit and scope of the appended claims should not be limited to the description of the preferred embodiment contained therein.

Claims

We Claim:

1. A compound represented by Formula I

Formula (I)

Q represents a bicyclic group selected from formula

their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, and pharmaceutical compositions thereof,

Wherein

** represents point of attachment of T;

# represents point of attachment of Y;

U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, alkenyl, alkynyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; T is a monocyclic or a bicyclic ring system which is saturated, unsaturated or partially unsaturated ring system and optionally have additional heteroatoms selected from O, N or S, and said ring is optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, - (CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, - NR⁷C(0)R⁸, -OS(0)_pR⁸, -NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, - (CR⁷R⁸)_nS(0)_pNR⁷R⁸, -(CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, - C(R⁷R⁸)_nCO(R⁷) and -S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵ independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

R² and R³ are independently selected from halogen, hydroxyl, cyano,

C2- C 6¾lkynyl, haloalkyl, perhaloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, or arylalkyl;

p = 0-2;

m = 0-2;

n = 0-4

2. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, wherein U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R^a and R^b are independently selected from the group consisting of hydrogen, -OR⁷, halogen, haloalkyl, perhaloalkyl and alkyl; or R^a and R^b taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S; Z is -C(O)- or -S(0)p-;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, - NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, - (CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and - S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; or when R⁴ or R⁵ are more than one, then any 2 R⁴ or 2 R⁵ independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

p = 0-2;

m = 0-2;

n = 0-4

3. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, wherein U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

T is cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl;

p = 0-2;

m = 0-2;

n = 0-4

4. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, wherein U is selected from O, NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

wherein T is unsubstituted or substituted with 1 to 4 substituents independently selected from halogen, alkyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, - (CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl,heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

Y is a group selected from -C(O)- , -0-, -N(R⁷)-, and -(CR^aR^b);

R² and R³ are independently selected from halogen, hydroxyl, cyano, Ci^alkyl, haloalkyl, perhaloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, or arylalkyl; R⁶ is selected from hydrogen, alkyl, haloalkyl, alkoxy, carboxy, aminocarbonyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

7 8

p = 0-2;

m = 0-2;

n = 0-4

5. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, whereinU is selected from O, NR' or CR'R";

X¹, X X^J and G are independently selected from N or CR';

T is selected from cyclopropyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, phenyl, tetrahydroiuranyl, pyrrolidinyl, pyridinyl, tetrahydropyridinyl, tetrahydropyranyl, piperazinyl, benzodiaxolyl, tetrahydroquinolinyl, morpholinyl, tetrahydronaphthyridinyl, tetrahydrothienopyridinyl, furanyl, pyrimidinyl, oxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, indolyl, quinolinyl, isoquinolinyl or benzooxazolyl; wherein T is unsubstituted or substituted with 1 to 4 substituents independently selected from halogen, alkyl, nitro, cyano, -(CR^aR^b)_mOR⁶, -(CR^aR^b)_mSR⁶, - (CR^aR^b)_mNR⁷R⁸, oxo, alkylsulfonyl, -(CR^aR^b)_mCOOR⁶, -(CR^aR^b)_mC(0)NR⁷R⁸, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;

Y is a group selected from -C(O)- , and -(CR^aR^b);

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, tetrazolyl, tetrazolylalkyl, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, -S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, - NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, -(CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, - (CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, -C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and - S(0)_pC(R R⁵)_nC(0)0R^/; or when R or R are more than one, then any 2 R or 2 R independently is optionally, taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S;

p = 0-2;

m = 0-2;

n = 0-4

6. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, whereinU is selected from NR' or CR'R";

X¹, X², X³ and G are independently selected from N or CR';

R and R are independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, alkoxy, carboxy, hydroxyl, cyano, aryl or cycloalkyl, , or

R and R taken together form a monocyclic or a bicyclic ring system which is saturated or partially unsaturated and optionally have additional heteroatoms selected from O, N or S, said ring system is further optionally substituted with 1 to 4 substituents independently selected from halogen, alkyl, haloalkyl, nitro, cyano, alkoxy, amino, oxo, alkylsulfonyl, carboxy, cycloalkyl or aryl;

T is selected from cyclohexyl, cyclohexenyl, phenyl or pyridinyl;

Y is a group selected from -C(O)- and -(CR^aR^b);

p = 0-2;

m = 0-2;

n = 0-4

7. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, wherein U is CR'R";

X¹, X², X³ and G are independently selected from N or CR';

T is phenyl;

Y is -C(O)-;

R¹, R⁴ and R⁵ are independently selected from hydrogen, halogen, alkyl, hydroxy, alkoxy, amino, mono, di or tri substituted haloalkyl, nitrile, nitro, oxo, -NR⁷R⁸, -OR⁷, -S(0)_pR⁷, - S(0)_pNR⁷R⁸, -NR⁷S(0)_pR⁸, -NR⁷C(0)R⁸, -OS(0)_pR⁸, -NR⁷C(0)OR⁸, -(CR⁷R⁸)_nC(0)OR⁷, - (CR⁷R⁸)_n(CO)NR⁷R⁸, -(CR⁷R⁸)_nS(0)_pNR⁷R⁸, -(CR⁷R⁸)_nN(R⁷)C(0)R⁷, -(CR⁷R⁸)_nOR⁷, - C(R⁷R⁸)_nNR⁷R⁸, -C(R⁷R⁸)_nCO(R⁷) and -S(0)_pC(R⁷R⁸)_nC(0)OR⁷ _; ;

7 8

p = 0-2;

m = 1;

n = 0-4

8. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, which is methyl 4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate;

4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid ;

4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; methyl 4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3- yl]-3-fluoro-benzoate;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

ethyl 4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3-ene-l- carboxylate;

4-[l-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3-ene-l-carboxylic acid;

ethyl 4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3- yl]cyclohex-3-ene-l-carboxylate;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3- yl]cyclohex-3-ene- 1 -carboxylic acid;

ethyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoate; ethyl 4-[l-[2,6-bis(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoate; ethyl 4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3- yl]benzoate;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid; 4-[l-[2,6-bis(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid; 4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

4-[l-[2,6-bis(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoate;

ethyl 4-[l-(2-chloro-4,6-difluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate; 4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-2-fluoro-benzoic acid; methyl 4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-2-fluoro- benzoate;

4-[l -[2 -chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-2 -hydroxy- benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3,5- difluoro-benzoate ; 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3,5-difluoro- benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-2- methoxy-benzoate ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-2-methoxy- benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-2- fluoro-benzoate;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-2-fluoro- benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

ethyl 4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; methyl 4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4-[l-[2-chloro-6-(2,2,2-trifluoroethoxy)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

ethyl 4-[l-(2-bromo-6-hydroxy-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

ethyl 4-[l-(2-bromo-6-hydroxy-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate;

4-[l-(2-bromo-6-hydroxy-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; 4-[l-(2-bromo-6-hydroxy-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

ethyl 3-fluoro-4-[l-[2-fluoro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3- yl]benzoate;

ethyl 4-[l-[2-fluoro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoate; ethyl 4-[l-(2-bromo-6-fluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoate; 4-[l-(2-bromo-6-fluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; 4-[l-[2-fluoro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

3- fluoro-4-[l-[2-fluoro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

ethyl 4-[l-[2-bromo-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoate;

4- [l-[2-bromo-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid; ethyl 4-[l-(2-chloro-6-methoxy-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4-[l-(2-chloro-6-methoxy-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-nitro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; ethyl 4-[l-(2-chloro-6-nitro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoate; 4-[l-(2-chloro-6-nitro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

ethyl 4-[l-(2-chloro-6-nitro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate;

4-[2-[3-(4-carboxyphenyl)-4,5,6,7-tetrahydroindazole-l-carbonyl]-3-chloro- phenyl] benzoic acid;

4-[l-(2-bromo-6-chloro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

4-[l-(2-chloro-6-moφholino-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

ethyl 4-[l-(2-chloro-6-moφholino-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4-[l-(2-chloro-6-moφholino-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid; ethyl 4-[l-(2-chloro-6-moφholino-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate; 4-[l-(2-chloro-6-ethyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; 4-[l-(3,6-dichloro-2-fluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

methyl 4-[l-(2-chloro-6-phenyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4-[l-(2-chloro-6-phenyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; 4-[l-(2-chloro-6-cyclopropyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

methyl 4-[l-(2-chloro-6-cyclopropyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4-[l-(2,6-dichloro-3-fluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-bromo-6-chloro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-4,6-difluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2,6-dimethylbenzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; methyl 4-[l-(6-chloro-2,3-difluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4- [l-(6-chloro-2,3-difluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

5- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]pyridine-2- carboxylic acid;

4-[l-(2-chloro-3,6-difluoro-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-cyano-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid; ethyl 4-[l-(2-chloro-6-cyano-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoate; methyl 4-[l-(2,6-dichlorobenzoyl)-6,6-dimethyl-4-oxo-5,7-dihydroindazol-3-yl]benzoate; 4-[l-(2,6-dichlorobenzoyl)-6,6-dimethyl-4-oxo-3a,5,7,7a-tetrahydroindazol-3-yl]benzoic acid ;

methyl 4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-6,6-dimethyl-4-oxo-5,7- dihydroindazol-3-yl]benzoate;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-6,6-dimethyl-4-oxo-5,7- dihydroindazol-3-yl]benzoic acid;

4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]-3,4- diazatricyclo[5.2.1.0{2,6}]deca-2(6),4- dien-5- yl} benzoic acid;

4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]- 3,4-diazatricyclo[5.2.1.0{2,6}]deca-2(6),4- dien-5- yl}benzoate;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-3- yl]benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-

3- yl]benzoate;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-oxo-6,7-dihydro-5H-indazol-3- yl]benzoate;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-oxo-6,7-dihydro-5H-indazol-3-yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol- 3-yl]benzoic acid;

methyl 4-[ 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -5,6,7,8-tetrahydro-4H- cyclohepta[c]pyrazol-3-yl]benzoate; 4-[5-tert-butyl-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5-methyl-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5-methyl-4,5,6,7-tetrahydroindazol-3- yl]benzoate;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-oxo-6,7-dihydro-5H-indazol-3-yl]-3-fluoro- benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-7-methyl-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

ethyl 4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]benzoate

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]benzoic acid ; methyl 4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoate;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

ethyl 6-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]pyridine-

3- carboxylate;

ethyl 4-[3-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-l-yl]benzoate;

4- [3-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-l-yl]benzoic acid;

methyl 4-[3-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoate; 4-[3-(2,6-dichlorobenzoyl)-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindol-l-yl]benzoic acid;

ethyl 4-[3-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindol-l-yl]benzoate; methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-hydroxy-4,5,6,7-tetrahydroindazol-

3- yl]benzoate ;

methyl 4-[ 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -4-fluoro-4,5,6,7-tetrahydroindazol-3 - yl]benzoate ;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-fluoro-4,5,6,7-tetrahydroindazol-3- yl] benzoic acid ; 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4-hydroxy-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

sodium 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoate ;

[2-chloro-6-(trifluoromethyl)phenyl]-[3-(2-fluoro-4-methyl-phenyl)-4,5,6,7- tetrahydroindazol- 1 -yl]methanone ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-N,N- dimethyl -benzamide ;

[4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- phenyl] -morpholino-methanone ;

methyl 4-[ 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -4,4-difluoro-6,7-dihydro-5H-indazol-

3- yl]benzoate ;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,4-difluoro-6,7-dihydro-5H-indazol-3- yl] benzoic acid ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,4-difluoro-6,7-dihydro-5H-indazol-3-yl]-3- fluoro-benzoic acid;

methyl 4-[ 1 -[2-chloro-6-(trifluoromethyl)benzoyl] -4,4-difluoro-6,7-dihydro-5H-indazol- 3 -yl] -3 -fluoro-benzoate ;

ethyl 4-[3-(2,6-dichlorobenzoyl)-4-oxo-6,7-dihydro-5H-indol-l-yl]benzoate;

4-[3-(2,6-dichlorobenzoyl)-4-oxo-6,7-dihydro-5H-indol-l-yl]benzoic acid ;

tert-butyl l-[2-chloro-6-(trifluoromethyl)benzoyl]-3-(4-methoxycarbonylphenyl)-6,7- dihydro-5H-pyrazolo[4,3-b]pyridine-4-carboxylate ;

4-[4-tert-butoxycarbonyl-l-[2-chloro-6-(trifluoromethyl)benzoyl]-6,7-dihydro-5H- pyrazolo[4,3-b]pyridin-3-yl]benzoic acid ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrazolo[4,3-b]pyridin-3- yl] benzoic acid ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H-indazole-7,l'- cyclopentane]-3-yl]benzoic acid ;

methyl 4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate ;

4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid; methyl 4-[l-(3,5-dichloropyridine-4-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoate;

4-[l-(3,5-dichloropyridine-4-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2,4-dimethylpyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-4-methyl-pyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid;

ethyl 4-[l-(2-chloro-4-methyl-pyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoate;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

4-[l-(4,6-dichloropyrimidine-5-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid;

4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid; methyl 4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoate; 4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydrooxepino[2,3- c]pyrazol-l-yl]benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydrooxepino[2,3-c]pyrazol-l- yl]benzoic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydro-4H-oxocino[2,3- c]pyrazol-l-yl]pyridine-3-carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-5,6,7,8-tetrahydro-4H-oxocino[2,3-c]pyrazol-l- yl]benzoic acid;

4- [3-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6,7,8-tetrahydro-4H-oxocino[2,3-c]pyrazol- l-yl]benzoic acid;

5- [3-(2-chloro-6-methyl-benzoyl)-5,6,7,8-tetrahydro-4H-oxocino[2,3-c]pyrazol-l- yl]pyridine-2-carboxylic acid; 4- [3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol- 1 -yl]benzoic acid;

5- [3-(2,6-dichlorophenyl)sulfonyl-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol-

1- yl]pyridine-2-carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol- 1 -yl]benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-8,8-difluoro-4,5,6,7-tetrahydrocyclohepta[c]pyrazol-l- yl]benzoic acid;

6- [3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]spiro[5,6,7,8-tetrahydro-4H- cycloocta[c]pyrazole-9,l'-cyclopropane]-l-yl]pyridine-3-carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6,7,8-tetrahydro-4H- cycloocta[c]pyrazole-9,l'-cyclopropane]-l-yl]benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6,7,8-tetrahydro-4H-cycloocta[c]pyrazole-9,l'- cyclopropane] -l-yl]benzoic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl]pyridine-3-carboxylic acid;

2- [3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl]pyrimidine-5-carboxylic acid;

2-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]pyrimidine-5- carboxylic acid; 2-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]pyrimidine-5- carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol-l- yl]benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol- l-yl]benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-5,6,7,8-tetrahydro-4H-cyclohepta[c]pyrazol-l- yl]benzoic acid;

6-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7,8,9- hexahydrocycloocta[c]pyrazol- 1 -yl]pyridine-3-carboxylic acid;

4-[3-(2,6-dichlorophenyl)sulfonyl-4,5,6,7,8,9-hexahydrocycloocta[c]pyrazol-l- yl]benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7,8,9-hexahydrocycloocta[c]pyrazol-l- yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3- yl]benzenesulfonamide;

[4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]phenyl]-(l- piperidyl)methanone ;

azetidin-l-yl-[4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3- yl] phenyl] methanone ;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]Benzamide; 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3- yl]benzenesulfonamide;

(2-chloro-6-methyl-phenyl)-[3-[4-( 1 -piperidylsulfonyl)phenyl] -4,5,6,7-tetrahydroindol- 1 - yl]methanone;

[2-chloro-6-(trifluoromethyl)phenyl]-[3-(4-pyrrolidin-l-ylsulfonylphenyl)-4,5,6,7- tetrahydroindol- 1 -yl]methanone;

[3 -[4-(azetidin- 1 -ylsulfonyl)phenyl] -4,5 ,6,7-tetrahydroindol- 1 -yl] -(2-chloro-6-methyl- phenyl)methanone ;

[4-[3 -(2 -chloro-6-methyl-benzoyl)-4,5 ,6,7-tetrahydroindol- 1 -yl]phenyl] -( 1 , 1 -dioxo- 1 ,4- thiazinan-4-yl)methanone;

[4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]phenyl]-(l- piperidyl)methanone ;

[4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l-yl]phenyl]- pyrrolidin- 1 -yl-methanone;

azetidin-l-yl-[4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l- yl] phenyl] methanone ;

(2-chloro-6-methyl-phenyl)-[l-[4-(l-piperidylsulfonyl)phenyl]-4,5,6,7-tetrahydroindol-3- yl] methanone;

[2-chloro-6-(trifluoromethyl)phenyl]-[l-(4-pyrrolidin-l-ylsulfonylphenyl)-4,5,6,7- tetrahydroindol-3-yl]methanone;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l- yl]benzenesulfonamide;

[ 1 -[4-(azetidin- 1 -ylsulfonyl)phenyl] -4,5 ,6,7-tetrahydroindol-3 -yl] -(2-chloro-6-methyl- phenyl)methanone ; 4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-5-(3-hydroxyazetidine-l-carbonyl)- 4,5,6,7-tetrahydroindol-l-yl]benzoic acid;

l-(4-carboxyphenyl)-3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindole -5 -carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]me1hyl]-5-(3-hydroxyazetidine-l-carbonyl)- 4,5,6,7-tetrahydroindol-l-yl]benzoic acid;

l-(4-carboxyphenyl)-3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindole -5 -carboxylic acid;

4-[5-(azetidine-l-carbonyl)-3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrahydroindol- 1 -yl]benzoic acid;

(2-chloro-6-me1hyl-phenyl)-[l-(p-tolyl)-4,5,6,7-tetrahydroindol-3-yl]methanone;

[2-chloro-6-(trifluoromethyl)phenyl]-[l-(p-tolyl)-4,5,6,7-tetrahydroindol-3- yl]methanone;

3-(2,6-dichlorophenyl)sulfonyl-l-(p-tolyl)-4,5,6,7-tetrahydroindole;

3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-l-(p-tolyl)-4,5,6,7-tetrahydroindole; 3- (2,6-dichlorophenyl)sulfonyl-l-(p-tolyl)-4,5,6,7-tetrahydroindole;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindazole-6-carboxylic acid;

3- (4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindazole-6-carboxylic acid;

4-[6-(azetidine-l-carbonyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrahydroindazol-3-yl]benzoic acid;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazole- 6-carboxylic acid;

(2-chloro-6-me1hyl-phenyl)-[3-(p olyl)-4,5,6,7 etrahydroindazol-l-yl]methanone; [2-chloro-6-(trifluoromethyl)phenyl]-[3-(p-tolyl)-4,5,6,7-tetrahydroindazol-l- yl]methanone;

l-(2,6-dichlorophenyl)sulfonyl-3-(p-tolyl)-4,5,6,7-tetrahydroindazole;

l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-3-(p-tolyl)-4,5,6,7-tetrahydroindazole; l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-3-(p-tolyl)-4,5,6,7-tetrahydroindole; l-(2,6-dichlorophenyl)sulfonyl-3-(p-tolyl)-4,5,6,7-tetrahydroindole;

[2-chloro-6-(trifluoromethyl)phenyl]-[3-(p-tolyl)-4,5,6,7-tetrahydroindol-l- yl]methanone;

(2-chloro-6-methyl-phenyl)-[3-(p-tolyl)-4,5,6,7-tetrahydroindol-l-yl]methanone;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindole-6- carboxylic acid;

3- (4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindole-6- carboxylic acid;

4- [6-(azetidine-l-carbonyl)-l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7- tetrahydroindol-3 -yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-6-(3-hydroxyazetidine-l-carbonyl)-4,5,6,7- tetrahydroindol-3 -yl]benzoic acid;

4- [6-(azetidine-l-carbonyl)-l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7- tetrahydroindol-3 -yl]benzoic acid;

3-(4-carboxyphenyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindole-6-carboxylic acid; 4-[6-(azetidine-l-carbonyl)-l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7- tetrahydroindol-3 -yl]benzoic acid;

4-[3 -(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol- 1 -yl] -2-hydroxy- cyclohexanecarboxylic acid;

4-[3 -(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol- 1 -yl] -2-hydroxy- cyclohexanecarboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l-yl]-2- hydroxy-cyclohexanecarboxylic acid;

4-[3 -(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol- 1 -yl]cyclohexene- 1 - carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]cyclohexene- 1 -carboxylic acid;

4-[3 -(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol- 1 -yl]cyclohexene- 1 - carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l- yl] cyclohexanecarboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl] cyclohexanecarboxylic acid; 4-[3 -(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol- 1 -yl]cyclohex-3-ene- 1 - carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-l-yl]cyclohex-3- ene-1 -carboxylic acid;

4-[3 -(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol- 1 -yl]cyclohex-3-ene- 1 - carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]me1hyl]-4,5,6,7-tetraliydroindazol-l- yl]cyclohex-3-ene- 1 -carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]me11iyl]-4,5,6,7-tetrahydroindazol-l- yl]cyclohexanecarboxylic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]me11iyl]-4,5,6,7-tetrahydroindazol-3- yl]cyclohexanecarboxylic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]me11iyl]-4,5,6,7-tetrahydroindazol-3- yl]cyclohex-3-ene- 1 -carboxylic acid;

4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3-ene-l- carboxylic acid; 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]cyclohex-3- ene-l-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]piperidine-4- carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]me1hyl]-4,5,6,7-tetrahydroindazol-3-yl]-3,6- dihydro-2H-pyridine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3,6-dihydro-2H- pyridine-4-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3,6-dihydro- 2H-pyridine-4-carboxylic acid

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3,6-dihydro-2H- pyridine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3-hydroxy-piperidine- 4-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-hydroxy- piperidine-4-carboxylic acid; l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-hydroxy-piperidine- 4-carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]-3- hydroxy-piperidine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3-hydroxy-piperidine-4- carboxylic acid;

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]-3-hydroxy-piperidine-4- carboxylic acid;

l-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]-3,6-dihydro-2H-pyridine- 4-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]-3,6-dihydro-2H- pyridine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3,6-dihydro-2H-pyridine- 4-carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3- yl]piperidine-4-carboxylic acid;

l-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]piperidine-4-carboxylic acid;

l-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]piperidine-4- carboxylic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]cyclohex- 3 -ene-1 -carboxylic acid; 4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3-ene-l- carboxylic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3-ene- 1-carboxylic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]cyclohex-3-ene-l- carboxylic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-3-yl]cyclohexanecarboxylic acid;

4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]metnyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro- benzoic acid;

4-[l-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3-fluoro-benzoic acid; 4-[l-(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol-3-yl]-3-fluoro-benzoic acid;

4-[l-[[2-chloro-6-(trifluoromethyl)phenyl]me1hyl]-4,5,6,7 etrahydroindol-3-yl]-3-fluoro- benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]-hydroxy-methyl]-4,5,6,7-tetrahydroindol-l- yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-N-me1hyl-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindol-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfanyl-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenoxy]-4,5,6,7-tetrahydroindol-l-yl]-3-fluoro- benzoic acid;

4-[3-(2-chloro-6-methyl-phenyl)sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-N-me1hyl-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid; 4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]-hydroxy-methyl]-4,5,6,7-tetrahydroindazol-l- yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfonyl-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenyl]sulfanyl-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)anilino]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)phenoxy]-4,5,6,7-tetrahydroindazol-l-yl]-3-fluoro- benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,5a,6,6a-tetrahydro-4H-cyclopropa[e]indol-

3- yl]-3-fluoro-benzoic acid;

4- [3-(2,6-dichlorobenzoyl)-4,5,5a,6,7,7a-hexahydrocyclobuta[g]indol-l-yl]-3-fluoro- benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-5,5a,6,6a-tetrahydro-4H- cyclopropa[e]indazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)spiro[6,7-dihydro-5H-indole-4,l'-cyclopropane]-3-yl]-

3- fluoro-benzoic acid;

4- [l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[6,7-dihydro-5H-indole-4,r- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-6,7-dihydro-5H-pyrano[3,2-b]pyrrol-3-yl]-3- fluoro-benzoic acid; 4-[l-(2,6-dichlorobenzoyl)-6,7-dihydro-5H-pyrano[3,2-c]pyrazol-3-yl]-3-fluoro-benzoic acid;

4-[l-(2,6-dichlorobenzoyl)spiro[6,7-dihydro-5H-indazole-4, l'-cyclopropane]-3-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrazolo[4,3-b]pyridin-3- yl]-3-fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)spiro[6,7-dihydro-5H-indazole-4, l'-cyclopropane]-3- yl]-3-fluoro-benzoic acid;

4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[6,7-dihydro-5H-indazole-4,r- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-(2,6-dichlorobenzoyl)spiro[6,7-dihydro-5H-indole-4,l'-cyclopropane]-3-yl]-3- fluoro-benzoic acid;

4-[l-(2-chloro-6-methyl-benzoyl)-4,4-difluoro-6,7-dihydro-5H-indol-3-yl]-3-fluoro- benzoic acid; 4-[l-(2-chloro-6-methyl-benzoyl)-6,7-dihydro-5H-pyrano[3,2-b]pyrrol-3-yl]-3-fluoro- benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6-dihydro-4H-indazole-7, l'-cyclopropane]-l- yl]-3-fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrazolo[3,4-b]pyridin-l- yl] -3 -fluoro-benzoic acid;

4-[3-(2,6-dichlorobenzoyl)spiro[5,6-dihydro-4H-indazole-7, l'-cyclopropane]-l-yl]-3- fluoro-benzoic acid;

4-[3-(2,6-dichlorobenzoyl)-7,7-difluoro-5,6-dihydro-4H-indazol-l-yl]-3-fluoro-benzoic acid;

4-[3-(2-chloro-6-methyl-benzoyl)spiro[5,6-dihydro-4H-indole-7,r-cyclopropane]-l-yl]-

3 - fluoro-benzoic acid;

4- [3-(2-chloro-6-methyl-benzoyl)spiro[5,6-dihydro-4H-indole-7,r-cyclopropane]-l-yl]-

3 - fluoro-benzoic acid;

4- [3-[2-chloro-6-(trifluoromethyl)benzoyl]spiro[5,6-dihydro-4H-indole-7,r- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydropyrrolo[2,3-b]pyridin-l-yl]- 3 -fluoro-benzoic acid; 4-[5-(2-chloro-6-methyl-benzoyl)-3,4-dihydro-2H-pyrano[2,3-b]pyrrol-7-yl]-3-fluoro- benzoic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]me1hyl]-4,5,6,7 etrahydroindol-l-yl]cyclohex-

3- ene-l-carboxylic acid;

4- [3 -(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol- 1 -yl]cyclohex-3-ene- 1 - carboxylic acid;

4-[3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol-l-yl]cyclohex-3-ene- 1 -carboxylic acid;

4-[3-(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindol-l-yl]cyclohex-3-ene-l- carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-l- yl] cyclohexene- 1 -carboxylic acid;

4-[3 -(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindol- 1 -yl]cyclohexene- 1 -carboxylic acid; 4-[3 -[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindol- 1 -yljcyclohexene- 1 - carboxylic acid;

4-[3-[[2-chloro-6-(trifluoromethyl)^

hydroxy-cyclohexanecarboxylic acid

4-[3 -(2,6-dichlorophenyl)sulfonyl-4,5,6,7-tetrahydroindazol- 1 -yl] -2 -hydroxy- cyclohexanecarboxylic acid

4-[3 -(2-chloro-6-methyl-benzoyl)-4,5,6,7-tetrahydroindazol- 1 -yl] -2 -hydroxy- cyclohexanecarboxylic acid

4-[3 -[ 1 -[2-chloro-6-(trifluoromethyl)phenyl]cyclopropyl]-4,5,6,7-tetrahydroindazol- 1 - yl] benzoic acid

4-[3-[[2-chloro-6-(trifluoromethyl)phenyl]-difluoro-methyl]-4,5,6,7-tetrahydroindazol-l- yl] benzoic acid

4-[3 -[ 1 -(2-chloro-6-methyl-phenyl)cyclopentyl] -4,5,6,7-tetrahydroindazol- 1 -yl]benzoic acid

4-[l-[l-[2-chloro-6-(trifluoromethyl)phenyl]cyclobutyl]-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

4-[l-[4-(2-chloro-6-methyl-phenyl)tetrahydropyran-4-yl]-4,5,6,7-tetrahydroindol-3- yl]benzoic acid;

4-[5 -(2-chloro-6-methylbenzoyl)-3 ,4- diazatricyclo [5.2.1.0^Λ {2,6 } ]deca-2(6),4-dien-3 -yl] -

3- fluorobenzoic acid;

4- {5-[2-chloro-6-(trifluoromethyl)benzoyl]-3,4- diazatricyclo[5.2.2.0^A{2,6}]undeca- 2(6),4-dien-3- yl} -3 -fluorobenzoic acid; 4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5- diazatricyclo[6.2.1.0^A{2,6}]undeca- 2(6),3-dien-5- yl}-3-fluorobenzoic acid;

4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5- diazatricyclo[6.1.1.0^A{2,6}]deca-2(6),3- dien-5-yl}-3- fluorobenzoic acid;

4-{ l-[2-chloro-6-(trifluoromethyl)benzoyl]-

3H,4H,5H,5aH,6H,6aH-cyclopropa[e]indazol-3-yl}-3- fluorobenzoic acid;

4-[5-(2,6-dichlorobenzoyl)-3,4- diazatricyclo[6.2.1.0^A{2,6}]undeca-2(6),4-dien-3- yl]-3- fluorobenzoic acid;

4-[3-(2,6-dichlorobenzoyl)-lH,4H,5H,5aH,6H,7H,7aH- cyclobuta[g]indazol-l-yl] -3 -fluorobenzoic acid ;

4-[3-(2,6-dichlorobenzoyl)-lH,4H,5H,5aH,6H,7H,7aH- cyclobuta[g] indol- 1 -yl] -3 -fluorobenzoic acid;

4-[5-(2,6-dichlorobenzoyl)-3- azatricyclo[6.2.1.0^A{2,6}]undeca-2(6),4-dien-3-yl]-3- fluorobenzoic acid;

4-[3-(2-chloro-6-methylbenzoyl)-3- azatricyclo[5.2.1.0^A{2,6}]deca-2(6),4-dien-5-yl]-3- fluorobenzoic acid;

4-{3-[2-chloro-6-(trifluoromethyl)benzoyl]-3- azatricyclo[5.2.2.0^A{2,6}]undeca-2(6),4- dien-5-yl}-3- fluorobenzoic acid;

4-[5-(2,6-dichlorobenzoyl)-4,5- diazatricyclo[6.2.1.0^A{2,6}]undeca-2(6),3-dien-3- yl]-3- fluorobenzoic acid and

4-[3 -(2-chloro-6-methylbenzoyl)-3 ,4- diazatricyclo [5.2.1.0^A {2,6 } ]deca-2(6),4-dien-5 -yl] -

3- fluorobenzoic acid

6-[l-[4-(4-chloro-2-methyl-3-pyridyl)tetrahydropyran-4-yl]-4,5,6,7-tetrahydroindol-3- yl]pyridine-3-carboxylic acid;

4- [ 1 -[ 1 -[4-chloro-2-(trifluoromethyl)-3-pyridyl]cyclopropyl] -4,5,6,7-tetrahydroindol-3 - yl]benzoic acid;

6-[l-[l-[4-chloro-2-(trifluoromethyl)-3-pyridyl]cyclobutyl]-4,5,6,7-tetrahydroindazol-3- yl]pyridine-3-carboxylic acid; 6-[3-[[2-chloro-4-(trifluoromethyl)-3-pyridyl]methyl]-5,6,7,8-tetrahydro-4H- oxocino[2,3-c]pyrazol-l-yl]pyridine-3-carboxylic acid;

5- [3-[(2,4-dichloro-3-pyridyl)sulfonyl]-8,8-difluoro-4,5,6,7- tetrahydrocyclohepta[c]pyrazol- 1 -yl]pyridine-2-carboxylic acid;

6- [3-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindazol-l- yl]pyridine-3-carboxylic acid;

6-[3-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindazol-l- yl]pyridine-3-carboxylic acid;

4-[l-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-3- yl]benzenesulfonamide;

(4-chloro-2-methyl-3-pyridyl)-[3-[4-(l-piperidylsulfonyl)phenyl]-4,5,6,7- tetrahydroindol- 1 -yl]methanone;

4- [3-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-l- yl]benzenesulfonamide;

l-(4-carboxyphenyl)-3-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]sulfonyl]-4,5,6,7- tetrahydroindole -5 -carboxylic acid;

l-(4-carboxyphenyl)-3-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7- tetrahydroindole -5 -carboxylic acid;

5- [l-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3- yl] bicyclo [2.2.2] octane -2-carboxylic acid;

l-[l-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3-yl]-3,6- dihydro-2H-pyridine-4-carboxylic acid;

l-[l-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4,5,6,7-tetrahydroindol-3- yl]piperidine-4-carboxylic acid; 4-[l-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3- yl]cyclohexanecarboxylic acid;

4-[l-[[4-chloro-2-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindol-3- yl]cyclohex-3-ene- 1 -carboxylic acid;

4-[l-[3-chloro-5-(trifluoromethyl)pyridazin-4-yl]sulfonyl-4,5,6,7-tetrahydroindazol-3- yl]-3-fluoro-benzoic acid;

4-[l-[4-chloro-6-(trifluoromethyl)pyrimidin-5-yl]sulfonyl-4,5,6,7-tetrahydroindazol-3- yl]benzoic acid;

4-[l-[[2-chloro-4-(trifluoromethyl)-3-pyridyl]methyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid;

4-[3 -[[2-chloro-4-(trifluoromethyl)-3-pyridyl]methyl] -4,5,6,7-tetrahydroindazol- 1 -yl] -3- fluoro-benzoic acid;

4-[3-[[2-chloro-4-(trifluoromethyl)-3-pyridyl]oxy]-4,5,6,7-tetrahydroindazol-l-yl]-3- fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)-5,5a,6,6a-tetrahydro-4H- cyclopropa[g] indol- 1 -yl] -3 -fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)-4a,5,5a,6-tetrahydro-4H-cyclopropa[f]indol-l-yl]- 3 -fluoro-benzoic acid; 4-[3-(2,4-dichloropyridine-3-carbonyl)-4,5,5a,6,7,7a-hexahydrocyclobuta[g]indol-l-yl]-

3- fluoro-benzoic acid;

4- [l-[4-chloro-2-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindol-3-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydropyrrolo[3,2- b]pyridin-3 -yl] -3 -fluoro-benzoic acid;

4-[l-(2-chloro-4-methyl-pyridine-3-carbonyl)spiro[6,7-dihydro-5H-indole-4,l'- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[6,7-dihydro-5H-indole-4, l'- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-6,7-dihydro-5H-pyrano[3,2- b]pyrrol-3 -yl] -3 -fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[6,7-dihydro-5H-indazole- 4, 1 '-cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-(2,4-dichloropyridine-3-carbonyl)spiro[6,7-dihydro-5H-indazole-4,l'- cyclopropane] -3 -yl] -3 -fluoro-benzoic acid;

4-[l-(2-chloro-4-methyl-pyridine-3-carbonyl)-6,7-dihydro-5H-pyrano[3,2-c]pyrazol-3- yl] -3 -fluoro-benzoic acid;

4-[l-(2,4-dichloropyridine-3-carbonyl)-4,4-difluoro-6,7-dihydro-5H-indazol-3-yl]-3- fluoro-benzoic acid;

4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydropyrazolo[4,3- b] pyridin-3 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]spiro[5,6-dihydro-4H-indazole- 7, 1 '-cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-5,6-dihydro-4H-pyrano[2,3- c] pyrazol- 1 -yl] -3 -fluoro-benzoic acid; 4-[3-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydropyrazolo[3,4- b]pyridin- 1 -yl] -3 -fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)-5,6-dihydro-4H-pyrano[2,3-c]pyrazol-l- yl] -3 -fluoro-benzoic acid;

4-[3-(2-chloro-4-methyl-pyridine-3-carbonyl)-7,7-difluoro-5,6-dihydro-4H-indazol-l-yl]-

3 - fluoro-benzoic acid;

4- [3 -(2,4-dichloropyridine-3 -carbonyl)-7,7-difluoro-5 ,6-dihydro-4H-indazol- 1 -yl] -3 - fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)spiro[5,6-dihydro-4H-indazole-7,l'- cyclopropane] - 1 -yl] -3 -fluoro-benzoic acid;

4-[3-(2,4-dichloropyridine-3-carbonyl)-5,6-dihydro-4H-pyrano[2,3-c]pyrazol-l-yl]-3- fluoro-benzoic acid;

4-[5-(2-chloro-4-methyl-pyridine-3-carbonyl)-3,4-dihydro-2H-pyrano[2,3-b]pyrrol-7-yl]-

3 - fluoro-benzoic acid;

4- [3-(4-chloro-2-methyl-pyridine-3-carbonyl)-7,7-difluoro-5,6-dihydro-4H-indol-l-yl]-3- fluoro-benzoic acid; and

4-[5-(2,4-dichloropyridine-3-carbonyl)-3,4-dihydro-2H-pyrano[2,3-b]pyrrol-7-yl]-3- fluoro-benzoic acid.

9. A compound of formula (I) as claimed in claim 1 or its tautomers, polymorphs,

stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, which is 4-[l-[2,6-bis(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid; methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoate; 4-[l-(2-chloro-6-moφholino-benzoyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluoro-benzoic acid;

methyl 4-[l-[2-chloro-6-(trifluoromethyl)benzoyl]-4,4-difluoro-6,7-dihydro-5H-indazol- 3 -yl] -3 -fluoro-benzoate ;

4-[l-(2,4-dichloropyridine-3-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]benzoic acid and 4-[l-[2-chloro-4-(trifluoromethyl)pyridine-3-carbonyl]-4,5,6,7-tetrahydroindazol-3-yl]-3- fluoro-benzoic acid.

10. A process of preparation of compounds of formula (I) as claimed in any of claims 1 to 9 or its tautomers, polymorphs, stereoisomers, prodrugs, solvate, co-crystals or pharmaceutically acceptable salts thereof.

11. A pharmaceutical composition comprising, as an active ingredient, at least one compound of formula (I), as claimed in any of the claims 1 to 9, or its tautomers, polymorphs, stereoisomers, prodrugs, solvate or a pharmaceutically acceptable salts thereof, together with one or more pharmaceutically acceptable carriers or excipients.

12. The pharmaceutical composition of claim 11, further comprising at least one additional therapeutically active agent.

13. A method of treating a retinoic acid-related orphan receptor gamma (RORy) mediated disease, disorder, syndrome or condition in a subject comprising administering an effective amount of a compound according to any one of claims 1 to 9.

14. The method according to claim 13, wherein the disease is an inflammatory or autoimmune disease.

15. The method according to claim 13, wherein the disease, disorder, syndrome or condition is rheumatoid arthritis, psoriasis, systemic lupus erythromatosis, lupus nephritis, scleroderma, chronic obstructive pulmonary disease (COPD), asthma, allergic rhinitis, allergic eczema, multiple sclerosis, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, type I diabetes, inflammatory bowel disease, graft versus host disease, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, uveitis, non-radio graphic spondyloarthropathy, chronic pain, acute pain, inflammatory pain, arthritic pain, neuropathic pain, post-operative pain, surgical pain, visceral pain, dental pain, premenstrual pain, central pain, cancer pain, pain due to burns, migraine or cluster headaches, nerve injury, neuritis, neuralgias, poisoning, ischemic injury, interstitial cystitis, viral, parasitic or bacterial infection, post-traumatic injury, or pain associated with irritable bowel syndrome.

16. A method of treatment of disease, disorder, syndrome or condition is selected from the group consisting of chronic obstructive pulmonary disease (COPD), asthma, cough, pain, inflammatory pain, chronic pain, acute pain, arthritis, osteoarthritis, multiple sclerosis, rheumatoid arthritis, colitis, ulcerative colitis and inflammatory bowel disease comprising administering to a subject in need thereof a compound according to any one of claims 1 to 9.