IP Library › Granted Patent US 11,008,340

Granted Patent B2

US 11,008,340 · App. 15/776,836 · Granted May 18, 2021

Modulators of ROR-gamma

Inventors: David A. Claremon (Maple Glen, PA); Lawrence Wayne Dillard (Yardley, PA); Yi Fan (Doylestown, PA); Lanqi Jia (Horsham, PA); Suresh B. Singh (Kendall Park, NJ); Colin M. Tice (Maple Glen, PA); Zhenrong Xu (Chalfont, PA); Jing Yuan (Lansdale, PA); Linghang Zhuang (Chalfont, PA)

Assignee: Vitae Pharmaceuticals, LLC

C07D513/04 C07D217/04 C07D217/24 C07D231/56 C07D239/88 C07D401/06 C07D401/12 C07D401/14 C07D405/12 C07D471/04

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Quick Facts

Patent No.: US 11,008,340
App. No.: 15/776,836
Granted: May 18, 2021
Kind: B2

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Abstract

Provided are novel compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

Claims (236)

1. A compound having the Formula IIIa, IVa, Va′, VIa′, VIIa″, VIIb″, VIIc″, VIIIa″, VIIIb″, or IXa′:

or a pharmaceutically acceptable salt thereof, wherein

p is independently 0 or 1;

L 2 is a bond or is selected from CH 2 , CH 2 CH 2 , CHMe, O, C(═O), CH(OH), and CH 2 O, wherein the oxygen or carbon atom in CH 2 O can be attached to Cy 2 ;

Cy 1 is selected from aryl, heteroaryl, heterocyclyl, and cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl, and cycloalkyl are each substituted with 1 to 3 groups independently selected from R 5 , wherein at least one R 5 is —SO 2 —(C 1 -C 3 )alkyl;

Cy 2 is selected from aryl, heteroaryl, monocyclic cycloalkyl, and monocyclic heterocyclyl, wherein the aryl, heteroaryl, monocyclic cycloalkyl, and monocyclic heterocyclyl are each optionally substituted with 1 to 3 groups independently selected from R 6 ;

R 2a is H, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 1 -C 4 )haloalkyl, or monocyclic cycloalkyl;

R 5 and R 6 are each independently selected from halogen, —CN, —OR c , —NR d R e , —S(O) k R c , —NR c S(O) 2 R c , —S(O) 2 NR d R e , —C(═O)OR c , —OC(═O)OR c , —OC(═O)R c , —OC(═S)OR c , —C(═S)OR c , —OC(═S)R c , —C(═O)NR d R e , —NR c C(═O)R c , —C(═S)NR d R e , —NR c C(═S)R c , —NR c C(═O)OR c , —OC(═O)NR d R e , —NR c (C═S)OR c , —OC(═S)NR d R e , —NR c C(═O)NR d R e , —NR c (C═S)NR d R e , —C(═S)R c , —C(═O)R c , (C 1 -C 6 )alkyl, cycloalkyl, —(CH 2 ) 14 -cycloalkyl, heterocyclyl, —(CH 2 ) 1-4 -heterocyclyl, aryl, —NHC(═O)-heterocyclyl, —NHC(═O)-cycloalkyl, —(CH 2 ) 1-4 -aryl, heteroaryl and —(CH 2 ) 1-4 -heteroaryl,

wherein the alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl portion present in each of said (C 1 -C 6 )alkyl, cycloalkyl, —(CH 2 ) 1-4 -cycloalkyl, heterocyclyl, —(CH 2 ) 1-4 -heterocyclyl, aryl, —(CH 2 ) 1-4 -aryl, heteroaryl and —(CH 2 ) 1-4 -heteroaryl substituent for R 6 are optionally substituted with halogen, OR c , —NO 2 , —CN, —NR c C(═O)R c , —NR d R e , —S(O) k R c , —C(═O)OR c , —C(═O)NR d R e , —C(═O)R c , (C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, or halo(C 1 -C 3 )alkoxy;

each R c is independently selected from hydrogen and (C 1 -C 6 )alkyl optionally substituted with hydroxy, (C 1 -C 2 )alkoxy, —C(O)NH 2 , —C(O)O(C 1 -C 3 )alkyl, or 1 to 3 halogen;

each R d and R e is independently selected from hydrogen and (C 1 -C 6 )alkyl;

k is 0, 1 or 2;

any heterocyclyl or heteroaryl portion of Cy 1 or Cy 2 is further optionally substituted with ═O;

R 7 is hydrogen, OR c , or (C 1 -C 3 )alkyl, wherein the (C 1 -C 3 )alkyl is optionally substituted with OR c or —NR d R e ; and

R 10 is (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )haloalkoxy, halo, cyano, or monocyclic cycloalkyl.

2. The compound of claim 1 , wherein R 10 is (C 1 -C 4 )alkyl; and L 2 is CH 2 O, wherein the methylene portion of CH 2 O is attached to Cy 2 .

3. The compound of claim 1 , wherein R 2 is (C 1 -C 4 )alkyl or cyclopropyl.

4. The compound of claim 1 , wherein R 7 is hydrogen, —O(C 1 -C 3 )alkyl, or (C 1 -C 3 )alkyl, wherein the (C 1 -C 3 )alkyl is optionally substituted with OH, NH 2 or N(C 1 -C 3 alkyl) 2 .

5. The compound of claim 1 , wherein Cy 1 is aryl or heteroaryl, each substituted with 1 to 3 groups independently selected from R 5 .

6. The compound of claim 1 , wherein Cy 1 is phenyl or pyridinyl, each substituted with 1 to 3 groups independently selected from R 5 .

7. The compound of claim 1 , wherein Cy 2 is phenyl, pyrimidinyl, cyclohexyl, pyridinyl, tetrahydropyranyl, or piperidinyl, each optionally substituted with 1 to 3 groups independently selected from R 6 .

8. The compound of claim 1 , wherein Cy 2 is phenyl or cyclohexyl, each optionally substituted with 1 to 3 groups independently selected from R 6 .

9. The compound of claim 1 , wherein

R 5 is selected from halogen, —CN, —OR c , —NR d R e , —NR c S(O) 2 R c , —S(O) 2 NR d R e , —C(═O)OR c , —C(═O)NR d R e , —NR c C(═O)R c , —NR c C(═O)OR c , —OC(═S)NR d R e , —C(═O)R c , —SO 2 —(C 1 -C 3 )alkyl, and (C 1 -C 4 )alkyl optionally substituted with halogen; and

R 6 is selected from halogen, —CN, —OR c , —NR d R e , —NR c S(O) 2 R c , —S(O) 2 NR d R e , —C(═O)OR c , —OC(═O)OR c , —OC(═O)R c , —C(═O)NR d R e , —NR c C(═O)R c , —C(═S)NR d R e , —NR c C(═S)R c , —NR c C(═O)OR c , —OC(═O)NR d R e , —NR c (C═S)OR c , —OC(═S)NR d R e , —NR c C(═O)NR d R e , —NR c (C═S)NR d R e , —C(═S)R c , —C(═O)R c , —SO 2 —(C 1 -C 3 )alkyl, and (C 1 -C 4 )alkyl optionally substituted with halogen.

10. The compound of claim 1 , wherein

R 5 is —SO 2 —(C 1 -C 3 )alkyl;

R 6 is selected from CN, halo, —C(═O)OR c , OR c , and (C 1 -C 4 )alkyl optionally substituted with halogen; and

R c is (C 1 -C 4 )alkyl optionally substituted with halogen.

11. The compound of claim 1 , wherein R 10 is (C 1 -C 4 )alkyl or halo.

12. The compound of claim 1 , wherein L 2 is a bond or is selected from CH 2 , O, and CH 2 O, wherein the carbon atom in CH 2 O is attached to a carbon atom on Cy 2 .

13. A compound selected from one of the following or a pharmaceutically acceptable salt thereof:

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1 ((tetrahydro-2H-pyran-4-yl)methoxy)isoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((4-(trifluoromethyl)phenoxy)isoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((4-(trifluoromethyl)cyclohexyl)oxy)isoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((4-(trifluoromethyl)benzyl)oxy)isoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-3-methyl-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-((4-(trifluoromethyl)benzyl)oxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

3-chloro-N-(4-(ethylsulfonyl)benzyl)-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

3-chloro-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-((-4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

1-((3,3-difluorocyclobutyl)methoxy)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methylisoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-((4-fluorobenzyl)oxy)-3-methylisoquinoline-6-carboxamide;

1-((4,4-difluorocyclohexyl)methoxy)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methylisoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-(4-(trifluoromethoxy)phenoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-((-4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)oxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-((6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-((-6-(trifluoromethyl)tetrahydro-2H-pyran-3-yl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methyl-1-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)methoxy)isoquinoline-6-carboxamide;

3-ethyl-N-(4-(ethylsulfonyl)benzyl)-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

3-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-3-methyl-1-((4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-3-methoxy-1-((-4-(trifluoromethyl)cyclohexyl)methoxy)isoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-((4-(trifluoromethyl)phenoxy)methyl)isoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-2-methyl-4-((4-(trifluoromethyl)benzyl)oxy)quinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-2-methyl-4-((4-(trifluoromethyl)cyclohexyl)methoxy)quinoline-7-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-methyl-4-((4-(trifluoromethyl)benzyl)oxy)quinoline-7-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-methyl-4-((4-(trifluoromethyl)cyclohexyl)methoxy)quinoline-7-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-4-((4-(trifluoromethyl)cyclohexyl)methoxy)quinazoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-((4-(trifluoromethyl)cyclohexyl)methoxy)quinazoline-7-carboxamide;

2-(5-cyanopyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-2-(4-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

ethyl (S)-2-(6-((4-(ethylsulfonyl)benzyl)carbamoyl)-1-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)pyrimidine-5-carboxylate;

ethyl 2-(6-((4-(ethylsulfonyl)benzyl)carbamoyl)-1-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)pyrimidine-5-carboxylate;

ethyl 2-(6-((4-(ethylsulfonyl)benzyl)carbamoyl)-1-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate;

2-(4-fluorobenzyl)-1-methyl-N-(4-(methylsulfonyl)benzyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-cyanobenzyl)-1-methyl-N-(4-(methylsulfonyl)benzyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-2-(4-fluorobenzyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-chlorobenzyl)-1-methyl-N-(4-(methylsulfonyl)benzyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-cyanobenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-chlorobenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-2-((5-methylpyrimidin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-2-(4-fluorobenzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-cyanobenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-((5-cyanopyridin-2-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-((6-cyanopyridin-3-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)ethyl)-1-isopropyl-2-((5-methylpyrazin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide 2-(4-chlorobenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-chlorobenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-((5-chloropyridin-2-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-4,4-dimethyl-2-((5-methylpyrazin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-(4-cyanobenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

methyl 4-((6-((4-(ethylsulfonyl)benzyl)carbamoyl)-1-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidine-1-carboxylate;

2-((6-(difluoromethoxy)pyridin-3-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

2-((5-bromopyrimidin-2-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

1-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

1-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

1-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide;

7-(5-cyanopyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

7-(5-chloropyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-7-(5-(trifluoromethyl)pyrimidin-2-yl)-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

ethyl 2-(3-((4-(ethylsulfonyl)benzyl)carbamoyl)-8-isopropyl-5,8-dihydro-1,7-naphthyridin-7(6H)-yl)pyrimidine-5-carboxylate;

ethyl 2-(3-((4-(ethylsulfonyl)benzyl)carbamoyl)-8-isopropyl-5,8-dihydro-1,7-naphthyridin-7(6H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate;

N-(4-(ethylsulfonyl)benzyl)-7-(4-fluorobenzyl)-8-isopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

7-(4-cyanobenzyl)-N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

7-(4-chlorobenzyl)-N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-8-isopropyl-7-((4-(trifluoromethyl)cyclohexyl)methyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-8-isopropyl-7-((4-(trifluoromethyl)cyclohexyl)methyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxamide;

3-cyclopropyl-N-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-indazole-6-carboxamide

3-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-indazole-6-carboxamide;

3-cyclopropyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-indazole-6-carboxamide;

3-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzyl)-2H-indazole-6-carboxamide;

3-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-indazole-6-carboxamide;

3-cyclopropyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-indazole-6-carboxamide;

3-cyclopropyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)benzyl)-2H-indazole-6-carboxamide;

3-cyclopropyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-pyrazolo[4,3-b]pyridine-6-carboxamide;

3-cyclopropyl-N-(4-(ethylsulfonyl)benzyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-pyrazolo[4,3-b]pyridine-6-carboxamide;

3-cyclopropyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-pyrazolo[4,3-b]pyridine-6-carboxamide;

3-cyclopropyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-((4-(trifluoromethyl)cyclohexyl)methyl)-2H-pyrazolo[4,3-b]pyridine-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-methyl-7-((4-(trifluoromethyl)cyclohexyl)methoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-methyl-7-((4-(trifluoromethyl)cyclohexyl)methoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-methyl-7-((4-(trifluoromethyl)benzyl)oxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-methyl-7-((4-(trifluoromethyl)benzyl)oxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-7-((4-(trifluoromethyl)cyclohexyl)methoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-methyl-7-(4-(trifluoromethyl)phenoxy)-1H-pyrrolo[2,3-c]pyridine-3-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-7-((4-(trifluoromethyl)cyclohexyl)methoxy)-1H-pyrrolo[2,3-c]pyridine-3-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-methyl-7-((4-(trifluoromethyl)benzyl)oxy)-1H-pyrrolo[2,3-c]pyridine-3-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-methyl-7-((4-(trifluoromethyl)cyclohexyl)methoxy)-1H-pyrrolo[2,3-c]pyridine-3-carboxamide;

N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1-methyl-7-((4-(trifluoromethyl)cyclohexyl)methoxy)-1H-pyrrolo[2,3-c]pyridine-3-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-2,5-dimethyl-4-((4-(trifluoromethyl)benzyl)oxy)thieno[2,3-d]pyrimidine-6-carboxamide

N-(4-(ethylsulfonyl)benzyl)-2,5-dimethyl-4-((4-(trifluoromethyl)cyclohexyl)methoxy)thieno[2,3-d]pyrimidine-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2,5-dimethyl-4-((4-(trifluoromethyl)benzyl)oxy)thieno[2,3-d]pyrimidine-6-carboxamide;

N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2,5-dimethyl-4-((4-(trifluoromethyl)cyclohexyl)methoxy)thieno[2,3-d]pyrimidine-6-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-2-(5-fluoropyrimidin-2-yl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(5-cyanopyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(5-chloropyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(5-cyclopropylpyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(5-ethoxypyrimidin-2-yl)-N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(5-chloropyrimidin-2-yl)-4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(5-(trifluoromethyl)pyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(5-cyclopropylpyrimidin-2-yl)-4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-1-oxo-2-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(3-methyl-5-(trifluoromethyl)pyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(4-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

ethyl 2-(7-((4-(ethylsulfonyl)benzyl)carbamoyl)-4-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)pyrimidine-5-carboxylate;

4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(5-morpholinopyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(5-(6-methoxypyridin-2-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(5-(6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(3-methyl-5-(trifluoromethyl)pyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(5-(2-methoxypyridin-4-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-2-(5-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

ethyl 2-(7-((4-(ethylsulfonyl)benzyl)carbamoyl)-4-isopropyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate;

N-(4-(ethylsulfonyl)benzyl)-2-(4-fluorobenzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(4-cyanobenzyl)-N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(4-chlorobenzyl)-N-(4-(ethylsulfonyl)benzyl)-4-isopropyl-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(tetrahydro-2H-pyran-4-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(4-(ethylsulfonyl)benzyl)-2-(5-(oxazol-2-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(4,4-difluorocyclohexyl)-4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(5-(oxazol-2-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide; and

4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(5-(oxazol-2-yl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

ethyl 2-(4-ethyl-7-((1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyrimidine-5-carboxylate;

4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(4-(trifluoromethyl)cyclohexyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-4-(trifluoromethyl)-2-(5-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(3-cyano-5-(trifluoromethyl)pyridin-2-yl)-4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

2-(3-cyano-5-(trifluoromethyl)pyridin-2-yl)-4-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide; and

N-(4-(ethylsulfonyl)benzyl)-8,8-dimethyl-6-(5-(trifluoromethyl)pyrimidin-2-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxamide.

14. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignments (2)

CHANGE OF NAME Recorded Mar 20, 2019

From: VITAE PHARMACEUTICALS, INC.

To: VITAE PHARMACEUTICALS, LLC

Reel/Frame 050150/0044 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 7, 2018

From: CLAREMON, DAVID A.; DILLARD, LAWRENCE WAYNE; FAN, YI; JIA, LANQI; SINGH, SURESH B.; TICE, COLIN M.; XU, ZHENRONG; YUAN, JING; ZHUANG, LINGHANG

To: VITAE PHARMACEUTICALS, INC.

Reel/Frame 046814/0306 →

Continuity (3)

Provisional Application 62320805 · Apr 11, 2016

Provisional Application 62257964 · Nov 20, 2015

Related Publication 20190322687A1 · Oct 24, 2019