N-alkylated indole and indazole compounds as RORgammaT inhibitors and uses thereof

1. A compound according to Formula I

or a pharmaceutically acceptable salt or solvate thereof, wherein:

Y is CH, N or CR a ;

n=0, 1, 2, 3 or 4;

A 4 is CR 4 or N,

A 5 is CR 5 ,

A 6 is CR 6 ,

A 7 is CR 7 ,

R a is (C 1-4 )alkyl;

R 1 is one of the following:

(a) phenyl substituted with one, two, or three R 8 ;

(b) phenyl that is (i) substituted with an unsubstituted (C 3-5 )heterocycloalkyl, unsubstituted (C 3-5 )heteroaryl, or (C 3-7 )cycloalkyl optionally substituted with hydroxy, and (ii) optionally substituted with one or two R 8 ;

(c) pyridinyl, quinolinyl, benzooxadiazolyl, thiophenyl, isoxazolyl, or benzothiophenyl, each optionally substituted with one, two, or three R 8 ; or

(d) pyridinyl, quinolinyl, benzooxadiazolyl, thiophenyl, isoxazolyl, or benzothiophenyl, that is (i) substituted with an unsubstituted (C 3-5 )heterocycloalkyl, unsubstituted (C 3-5 )heteroaryl, or (C 3-7 )cycloalkyl optionally substituted with hydroxy, and (ii) optionally substituted with one or two R 8 ;

R 2 is hydroxycarbonyl, hydroxycarbonyl(C 1-10 )alkyl, (C 1-10 )alkylsulfoxyaminocarbonyl, or carbamoyl;

R 3 is hydrogen, halogen, cyano, nitro, hydroxy, (C1-3)alkylC(O)O—, (C 1-4 )alkyl, or (C 1-4 )alkoxy, wherein (C 1-4 )alkyl and (C 1-4 )alkoxy are optionally substituted with one or more halogen;

R 4 , R 5 , R 6 and R 7 independently are H, halogen, amino, cyano, (C 1-4 )alkyl, (C 0-10 )alkyl)aminocarbonyl, or (di)(C 1-6 )alkylaminocarbonyl, wherein (C 1-3 )alkoxy and (C 1-4 )-alkyl are optionally substituted with one or more halogen, hydroxyl or (C 1-3 )alkoxy; or a group having the formula

optionally substituted with one or more of the following: (C 1-10 )alkyl, halogen, hydroxy, and (C 1-3 )alkoxy, wherein m is 1, 2, 3, or 4;

R 8 is halogen, cyano, hydroxy, (C 1-3 )alkoxycarbonyl, (C 1-4 )alkyl, or (C 1-3 )alkoxy, wherein (C 1-3 )alkoxycarbonyl, (C 1-4 )alkyl, and (C 1-3 )alkoxy are optionally substituted with hydroxy or one, two or three halogens; and

R 9 is hydrogen or (C 1-4 )alkyl.

2. The compound of claim 1 having Formula Ia

or a pharmaceutically acceptable salt or solvate thereof.

3. The compound of claim 1 having Formula Ib

or a pharmaceutically acceptable salt or solvate thereof.

4. The compound of claim 3 , wherein Y is N.

5. The compound of claim 3 having Formula Ic

or a pharmaceutically acceptable salt or solvate thereof.

6. The compound of claim 5 having Formula Id

or a pharmaceutically acceptable salt or solvate thereof.

7. The compound of claim 6 , wherein Y is N.

8. The compound of claim 2 having Formula Ie

wherein x is 1, 2, or 3,

or a pharmaceutically acceptable salt or solvate thereof.

9. The compound of claim 8 having Formula If

or a pharmaceutically acceptable salt or solvate thereof.

10. The compound of claim 9 having Formula Ig

or a pharmaceutically acceptable salt or solvate thereof.

11. The compound of claim 10 having Formula Ih

or a pharmaceutically acceptable salt or solvate thereof.

12. The compound of claim 1 , wherein R 1 is phenyl substituted with one or two R 8 .

13. The compound of claim 1 , wherein R 1 is phenyl substituted with one, two or three R 8 .

14. The compound of claim 13 , wherein R 2 is C(O)OH.

15. A compound selected from:

4-{1-[2-chloro-6-(trifluoromethyl)benzyl]-1H-pyrazolo[3,4-c]pyridin-3-yl}-3-fluorobenzoic acid;

4-[1-(2-bromo-6-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-{-1-[2-chloro-6-(trifluoromethyl)benzyl]-4-fluoro-1H-indazol-3-yl}-3-fluorobenzoic acid;

4-{-1-[2-chloro-6-(trifluoromethyl)benzyl]-4-fluoro-1H-indazol-3-yl}benzoic acid;

4-{-1-[2-chloro-6-(trifluoromethyl)benzyl]-4-fluoro-1H-indazol-3-yl}-2,5-difluorobenzoic acid;

4-(1-{1-[2-chloro-6-(trifluoromethyl)phenyl]ethyl}-4-fluoro-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-{(1R or 1S)-1-[2-chloro-6-(trifluoromethyl)phenyl]ethyl}-4-fluoro-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-{(1S or 1R)-1-[2-chloro-6-(trifluoromethyl)phenyl]ethyl}-4-fluoro-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-[1-(2-bromo-3-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(5-chloro-2-cyanobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

3-fluoro-4-(1-{-1-[2-(trifluoromethyl)phenyl]ethyl}-1H-pyrazolo[4,3-b]pyridin-3-yl)benzoic acid;

4-[1-(6-chloro-2-fluoro-3-methylbenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(2-chloro-3,6-difluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

3-fluoro-4-[1-(2,3,6-trifluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]benzoic acid;

3-fluoro-4-{1-[2-fluoro-6-(trifluoromethyl)benzyl]-1H-pyrazolo[4,3-b]pyridin-3-yl}benzoic acid;

4-[1-(2,6-difluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(2-chloro-6-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(6-chloro-2-fluoro-3-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(2-chloro-6-fluoro-3-methoxybenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(2,3-dichloro-6-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-[1-(1-benzothiophen-7-ylmethyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-{1-[2,6-dichloro-3-(trifluoromethyl)benzyl]-1H-pyrazolo[4,3-b]pyridin-3-yl}-3-fluorobenzoic acid;

4-[1-(3,6-dichloro-2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-{1-[2-chloro-6-(methoxycarbonyl)benzyl]-1H-pyrazolo[4,3-b]pyridin-3-yl}-3-fluorobenzoic acid;

4-[1-(2-bromo-6-chlorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl]-3-fluorobenzoic acid;

4-{1-[2-chloro-6-(trifluoromethyl)benzyl]-1H-pyrazolo[4,3-b]pyridin-3-yl}-3-fluorobenzoic acid;

4-{1-[2-chloro-6-(trifluoromethyl)benzyl]-1H-pyrrolo[3,2-b]pyridin-3-yl}-3-fluorobenzoic acid;

4-{1-[2-chloro-6-(trifluoromethyl)benzyl]-1H-pyrrolo[2,3-c]pyridin-3-yl}-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzyl)-1H-indazol-3-yl)-2-hydroxybenzoic acid;

3-Fluoro-4-[4-fluoro-1-(2-fluoro-6-methoxybenzyl)-1H-indazol-3-yl]benzoic acid;

3-fluoro-4-(4-fluoro-1-(3-(trifluoromethoxy)benzyl)-1H-indazol-3-yl)benzoic acid;

3-fluoro-4-[4-fluoro-1-(2-methoxybenzyl)-1H-indazol-3-yl]benzoic acid;

3-fluoro-4-{4-fluoro-1-[2-(1H-pyrazol-1-yl)benzyl]-1H-indazol-3-yl}benzoic acid;

4-[1-(2-cyanobenzyl)-4-fluoro-1H-indazol-3-yl]-3-fluorobenzoic acid;

3-fluoro-4-{4-fluoro-1-[2-fluoro-5-(trifluoromethoxy)benzyl]-1H-indazol-3-yl}benzoic acid;

4-[1-(2,6-dichlorobenzyl)-4-fluoro-1H-indazol-3-yl]-3-fluorobenzoic acid;

4-(1-(2,6-dichlorobenzyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3-fluorobenzoic acid;

4-(1-(2-bromo-6-(trifluoromethyl)benzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-chloro-6-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-benzyl-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-chloro-5-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-chloro-4-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-bromo-5-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(3-chloro-5-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(3, 5-dichlorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(4-bromo-2-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2,5-dichlorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

5-fluoro-4-(4-fluoro-1-(3-fluoro-5-(trifluoromethyl)benzyl)-1H-indazol-3-yl)-2-hydroxybenzoic acid;

5-fluoro-4-(4-fluoro-1-(2-fluoro-6-(trifluoromethyl)benzyl)-1H-indazol-3-yl)-2-hydroxybenzoic acid;

4-(1-(2-chloro-6-cyclopropylbenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-chloro-6-methylbenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-chloro-6-(1-hydroxycyclobutyl)benzyl)-4-fluoro-1H-indazol-3-yl)-3-fluorobenzoic acid;

5-fluoro-4-(4-fluoro-1-(2-methyl-6-(trifluoromethyl)benzyl)-1H-indazol-3-yl)-2-hydroxybenzoic acid;

5-fluoro-4-(4-fluoro-1-(2-(trifluoromethyl)benzyl)-1H-indazol-3-yl)-2-hydroxybenzoic acid;

4-(1-(2-ethyl-6-(trifluoromethyl)benzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

4-(1-(2-chloro-6-fluorobenzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid;

sodium 4-(1-(2-chloro-6-(trifluoromethyl)benzyl)-4-fluoro-6-(3-methoxyazetidine-1-carbonyl)-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoate;

4-(6-(azetidine-1-carbonyl)-1-(2-chloro-6-(trifluoromethyl)benzyl)-4-fluoro-1H-indazol-3-yl)-5-fluoro-2-hydroxybenzoic acid; and

4-(6-(azetidine-1-carbonyl)-1-(2-chloro-6-(trifluoromethyl)benzyl)-4-fluoro-1H-indazol-3-yl)-3-fluorobenzoic acid.

16. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, and one or more pharmaceutically acceptable excipients.

17. The pharmaceutical composition of claim 16 , further comprising at least one additional therapeutically active agent.

18. A method for treating a disease or condition mediated by RORgammaT in a subject comprising administering to the subject an amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, that is effective for treating the disease or condition mediated by RORgammaT in the subject, wherein the disease or condition is an autoimmune disease and wherein the compound of claim 1 is effective for treating an autoimmune disease in that subject.

19. A method for treating a disease or condition mediated by RORgammaT in a subject comprising administering to the subject an amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, that is effective for treating the disease or condition mediated by RORgammaT in the subject, wherein the disease or condition is multiple sclerosis, inflammatory bowel disease, Crohn's disease, ankylosing spondylitis, psoriasis, rheumatoid arthritis, asthma, osteoarthritis, Kawasaki disease, Hashimoto's thyroiditis or mucosal leishmaniasis.

20. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising a compound of claim 20 and one or more pharmaceutically acceptable excipients.

22. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition comprising a compound of claim 22 and one or more pharmaceutically acceptable excipients.