Granted Patent B2

US 9,745,265 · App. 14/421,048 · Granted Aug 29, 2017

Abstract

Claims (199)

1. A compound according to Formula I

or a pharmaceutically acceptable salt or solvate thereof, wherein:

Y is CH, CR a , or N;

n=0, 1, 2, or 3;

A 4 is N,

A 5 is CR 5 ,

A 6 is CR 6 ,

A 7 is CR 7 ,

R a is (C 1-4 )alkyl or (C 3-7 )cycloalkyl;

R 1 is

(i) (C 3-12 )carbocyclyl(C 0-4 )alkyl, or

(ii) a 4- to 12-membered heterocyclyl(C 0-4 )alkyl,

each being substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally one, two, or three other occurrences of R 8 ;

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

R 3 is hydrogen, halogen, cyano, nitro, hydroxy, (C 1-4 )alkylcarbonyloxy, (C 1-4 ) alkylsulfonylamino, (C 1-4 ) alkylcarbonylamino, (C 0-4 ) alkylamino, (C 1-4 )alkyl, hydroxyl(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 5 -R 7 independently are hydrogen, halogen, amino, cyano, hydroxy, (C 1-3 )alkoxy, (C 1-4 )-alkyl, (C 1-6 )alkylcarbonylamino, (C 1-4 )alkylamino, amino(C 1-4 )alkyl or —C(O)H, wherein (C 1-3 )alkoxy, (C 1-4 )alkyl, (C 1-4 )alkylamino and amino(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, or (C 1-3 )alkoxy, and wherein m is 1, 2, 3, or 4; or

R 6 is additionally selected from:

(i) (C 3-7 )cycloalkyl or (C 3-5 )heterocycloalkyl, both optionally substituted with one or more groups selected from halogen, amino, hydroxyl, oxo (═O), H 2 NC(O), (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen or hydroxyl;

(ii) (C 2-9 )heteroaryl, optionally substituted with one or more groups selected from halogen, amino, cyano, hydroxyl, H 2 NC(O), (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen, amino or hydroxyl;

(iii) (C 6-14 ) aryl, optionally substituted with one or more groups selected from halogen, amino, cyano, hydroxyl, H 2 NC(O), (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen, amino or hydroxyl;

(iv) (C 3-5 )heterocycloalkylcarbonyl or (C 3-5 )heterocycloalkylcarbonyl(C 1-4 )alkyl, optionally substituted with one or more groups selected from halogen, amino, hydroxyl, oxo (═O), H 2 NC(O), (C 1-3 )alkoxycarbonyl, (di)(C 1-6 )alkylaminocarbonyl, (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-3 )alkoxycarbonyl, (di)(C 1-6 )alkylaminocarbonyl, (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen, amino or hydroxyl;

(v) (C 3-5 )heterocycloalkylamino, (C 3-5 )cycloalkylaminocarbonyl, di(C 3-5 )cycloalkylaminocarbonyl, (C 3-5 )cycloalkylcarbonylamino, (C 3-5 )cycloalkyl(C 1-4 )alkyl, (C 3-5 )cycloalkylamino, or (C 3-5 )cycloalkylcarbonyl, each of which is optionally substituted with one or more groups selected from halogen, amino, hydroxyl, oxo (═O), H 2 NC(O), (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen or hydroxyl;

(vi) (C 2-9 )heteroaryl(C 1-4 )alkyl or (C 2-9 )heteroarylcarbonyl, optionally substituted with one or more groups selected from halogen, amino, cyano, hydroxyl, H 2 NC(O), (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen, amino or hydroxyl;

(vii) (C 2-4 )alkynyl, optionally substituted with hydroxyl or amino; or

(viii) (C 1-6 )alkylsulfonylamino(C 0-4 )alkyl,

(C 1-6 )alkylaminocarbonylamino,

(C 1-6 )alkoxycarbonylamino(C 0-4 )alkyl,

Hydroxycarbonyl(C 1-4 )alkylamino,

(C 0-6 )alkylaminocarbonyl(C 1-6 )alkyl, or

di(C 1-6 )alkylaminocarbonyl(C 1-6 )alkyl,

each optionally substituted with one or more (C 1-4 )alkyl, hydroxyl or amino; and

R 8 is halogen, cyano, oxo (═O), di(C 1-3 )alkylamino, (C 1-3 )alkoxycarbonyl, (di)(C 1-6 )alkylaminocarbonyl, (C 1-4 )alkyl, (C 3-7 )cycloalkyl, (C 3-5 )heterocycloalkyl, (C 1-4 )alkenyl, (C 3-6 )cycloalkoxy or (C 1-3 )alkoxy, wherein (C 1-3 )alkoxycarbonyl, (di)(C 1-6 )alkylaminocarbonyl, (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one, two or three halogens.

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, 3, or 4;

at least one occurrence of R 8 is (C 3-7 )cycloalkyl;

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; wherein at least one occurrence of R 8 is (C 3-7 )cycloalkyl.

10. The compound of claim 9 having Formula Ig

or a pharmaceutically acceptable salt or solvate thereof; wherein at least one occurrence of R 8 is (C 3-7 )cycloalkyl.

11. The compound of claim 10 having Formula Ih

or a pharmaceutically acceptable salt or solvate thereof; wherein R 8 is (C 3-7 )cycloalkyl.

12. The compound of claim 1 , wherein Y is N.

13. The compound of claim 1 , wherein R 1 is

(i) (C 3-7 )cycloalkyl or (C 3-5 )heterocycloalkyl, both being substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally one, two, or three other occurrences of R 8 ;

(ii) (C 2-9 )heteroaryl(C 0-4 )alkyl, being substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally with one, two, or three other occurrences of R 8 ; or

(iii) (C 6-14 )aryl(C 0-4 )alkyl, being substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally with one, two, or three other occurrences of R 8 .

14. The compound of claim 13 , wherein R 1 is (i) (C 2-9 )heteroaryl, or (ii) (C 6-14 )aryl, both substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally one, two, or three other occurrences of R 8 .

15. The compound of claim 14 , wherein R 1 is (C 6-14 ) aryl substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally one other occurrence of R 8 .

16. The compound of claim 15 , wherein R 1 is phenyl substituted with (i) one occurrence of R 8 that is (C 3-7 )cycloalkyl and (ii) optionally one other occurrence of R 8 .

17. The compound of claim 16 , wherein R 2 is C(O)OH.

18. The compound of claim 1 , wherein R 6 is

19. A compound selected from:

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

4-(1-(2-chloro-6-cyclypropoxybenzoyl)-1H-indazol-3-yl)benzoic acid;

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

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-4-formyl-1H-indazol-3-yl)benzoic acid;

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

3-fluoro-4-(1-(2-phenylpropanoyl)-1H-indazol-3-yl)benzoic acid;

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

3-fluoro-4-[1-(pyridin-3-ylcarbonyl)-1H-indazol-3-yl]benzoic acid;

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

3-fluoro-4-[1-(naphthalen-1-ylcarbonyl)-1H-indazol-3-yl]benzoic acid;

3-fluoro-4-{1-[(1-methyl-1H-indol-2-yl)carbonyl]-1H-indazol-3-yl}benzoic acid;

4-{1-[(2-bromo-3-methylphenyl)carbonyl]-1H-indazol-3-yl}-3-fluorobenzoic acid;

4-[1-(2,3-dihydro-1H-inden-4-ylcarbonyl)-1H-indazol-3-yl]-3-fluorobenzoic acid;

4-(1-{[3-(tertbutoxycarbonyl)-3-azabicyclo[3.1.0]hex-6-yl]carbonyl}-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-[1-(2,3-dihydro-1-benzofuran-7-ylcarbonyl)-1H-indazol-3-yl]-3-fluorobenzoic acid;

4-[1-(1-benzofuran-7-ylcarbonyl)-1H-indazol-3-yl]-3-fluorobenzoic acid;

4-{1-[(2-bromo-3-chlorophenyl)carbonyl]-1H-indazol-3-yl}-3-fluorobenzoic acid;

3-fluoro-4-(1-(tetrahydrofuran-2-carbonyl)-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(morpholine-4-carbonyl)-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-((2S,6R)-2,6-dimethylmorpholine-4-carbonyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(4-oxopiperidine-1-carbonyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

2-acetamido-4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-2-(methylsulfonamido)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl) benzoyl)-6-(3-hydroxyazetidin-1-yl)-1H-indazol-3-yl)benzoic acid;

4-(6-(azetidin-1-yl)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(cyclopropylamino)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(oxetan-3-ylamino)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-hydroxypyrrolidin-1-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-morpholino-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(methoxycarbonylamino)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(N-methylacetamido)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(cyclopropanecarboxamido)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(methylsulfonamido)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-methylureido)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(6-acetamido-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(N-methylmethylsulfonamido)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(1,3-dimethylureido)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(2-oxo-imidazolidin-1-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(2-oxoazetidin-1-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(6-(2-carboxyethylamino)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-methyl-2-oxoimidazolidin-1-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(2-oxopyrrolidin-1-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(morpholine-4-carbonyl)-1H-indazol-3-yl)benzoic acid;

3-(4-carboxyphenyl)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazole-6-carboxylic acid;

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

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(cyclopropyl(methyl)carbamoyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(cyclopropyl(hydroxy)methyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3-fluorobenzoic acid;

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

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(hydroxy(oxazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridine-3-yl)-3-fluorobenzoic acid;

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

sodium 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(5-methyloxazol-2-yl)-1H-indazol-3-yl)benzoate;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(5-methyloxazol-2-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-hydroxyprop-1-ynyl)-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-hydroxybut-1-ynyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(6-(3-aminoprop-1-ynyl)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-ethynyl-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-methyl-1,2,4-oxadiazol-5-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(5-(hydroxymethyl)oxazol-2-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(1-methyl-1H-imidazol-4-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(oxazol-2-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(6-(5-bromooxazol-2-yl)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

(E)-4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(N′-cyano-N,N-dimethylcarbamimidoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(4H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(1-methyl-1H-imidazol-2-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-[1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-6-(1-methyl-1H-imidazol-5-yl)-1H-indazol-3-yl]benzoic acid;

4-[1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-6-(5-methylthiophen-3-yl)-1H-indazol-3-yl]benzoic acid;

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

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

4-[1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-6-(1-methyl-1H-imidazol-4-yl)-1H-indazol-3-yl]benzoic acid;

4-[1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-6-(1,3-thiazol-4-yl)-1H-indazol-3-yl]benzoic acid;

4-(6-[4-(aminomethyl)pyridin-2-yl]-1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-1H-indazol-3-yl)benzoic acid;

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

4-[1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-6-(1,3-thiazol-5-yl)-1H-indazol-3-yl]benzoic acid;

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

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

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

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

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

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

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

4-[1-{[2-chloro-6-(trifluoromethyl)phenyl]carbonyl}-6-(1-methyl-1H-pyrazol-5-yl)-1H-indazol-3-yl]benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(methylsulfonamidomethyl)-1H-indazol-3-yl)benzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(2,5-dioxoimidazolidin-4-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

4-(5-(tert-butoxycarbonylamino)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-3-fluorobenzoic acid;

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

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

4-(5-acetamido-1-(2-chloro-6-(trifluoromethyl)-benzoyl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-5-(methylamino)-1H-pyrrolo[2,3-c]pyridin-3-yl)-3-fluorobenzoic acid;

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

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

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

4-(1-(6-chloro-2,3-dihydrobenzo[b][1,4]dioxine-5-carbonyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3-fluorobenzoic acid;

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

4-(4-chloro-1-(2-chloro-6-cyclopropylbenzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

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

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

4-(1-(2-chloro-6-cyclopropylbenzoyl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

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

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

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3,5-dimethylmorpholine-4-carbonyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3-fluorobenzoic acid;

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

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-2-methyl-1H-indol-3-yl)-3-fluorobenzoic acid;

4-(2-methyl-1-(2-(trifluoromethyl)benzoyl)-1H-indol-3-yl)benzoic acid;

4-(1-(2-chloro-6-cyclopropylbenzoyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3,5-difluorobenzoic acid;

4-(1-(2-chloro-6-cyclopropylbenzoyl)-1H-indazol-3-yl)-3,5-difluorobenzoic acid;

4-(1-(2-chloro-6-cyclopropylbenzoyl)-4-fluoro-1H-indazol-3-yl)-3,5-difluorobenzoic acid;

4-(1-(2-chloro-6-cyclopropylbenzoyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)-3,5-difluorobenzoic acid;

4-(1-(2-chloro-6-cyclobutylbenzoyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3,5-difluorobenzoic acid;

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

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

4-(6-(azetidine-1-carbonyl)-1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indol-3-yl)-3-fluorobenzoic acid;

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(3-methoxy-azetidine-1-carbonyl)-1H-indol-3-yl)-3-fluorobenzoic acid;

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

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

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

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

4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-6-(oxetan-3-yl)-1H-indazol-3-yl)-3-fluorobenzoic acid;

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

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

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

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

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

4-(1-(2-chloro-6-cyclobutylbenzoyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-3,5-difluorobenzoic acid.

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

21. The pharmaceutical composition of claim 20 , further comprising at least one additional therapeutically active agent.

22. 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.

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

24. The compound of claim 10 , wherein R 3 is hydrogen or halogen.

25. The compound of claim 24 , wherein R 5 and R 7 are hydrogen or halogen.

26. The compound of claim 25 , wherein R 6 is (C 3-5 )heterocycloalkylcarbonyl or (C 3-5 )heterocycloalkylcarbonyl(C 1-4 )alkyl, optionally substituted with one or more groups selected from halogen, amino, hydroxyl, oxo (═O), H 2 NC(O)—, (C 1-3 )alkoxycarbonyl, (di)(C 1-6 )alkylaminocarbonyl, (C 1-4 )alkyl or (C 1-3 )alkoxy, wherein (C 1-3 )alkoxycarbonyl, (di)(C 1-6 )alkylaminocarbonyl, (C 1-4 )alkyl and (C 1-3 )alkoxy are optionally substituted with one or more halogen, amino or hydroxyl.

27. The compound of claim 26 , wherein R 8 is halogen, (C 1-4 )alkyl, or (C 3-7 )cycloalkyl, wherein the (C 1-4 )alkyl is optionally substituted with one, two or three halogens.

28. A pharmaceutical composition comprising a compound of claim 27 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

29. 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 19 , or a pharmaceutically acceptable salt 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.

Assignments (8)