IP Library › Granted Patent US 10,829,481

Granted Patent B2

US 10,829,481 · App. 16/073,503 · Granted Nov 10, 2020

Benzimidazole derivatives as modulators of ROR-gamma

Inventors: David A. Claremon (Maple Glen, PA); Lawrence Wayne Dillard (Yardley, PA); Yi Fan (Doylestown, PA); Stephen D. Lotesta (Burlington, NJ); Suresh B. Singh (Kendall Park, NJ); Colin M. Tice (Maple Glen, PA); Wei Zhao (North Potomac, MD); Linghang Zhuang (Chalfont, PA)

Assignee: Vitae Pharmaceuticals, LLC

C07D405/14 C07D405/10

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Patent No.: US 10,829,481
App. No.: 16/073,503
Granted: Nov 10, 2020
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 RORy. 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 (183)

1. A compound of the Formula VI:

or a pharmaceutically acceptable salt thereof, wherein

A is N or CH;

R 1 is (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, or cycloalkyl optionally substituted with 1 to 3 halo;

L 2 is CH 2 or CHMe;

Cy 2 is bi-cyclic heterocyclyl or bi-cyclic heteroaryl, each of which are optionally substituted with 1 to 3 groups independently selected from halo, (C 1 -C 4 )alkyl, and (C 1 -C 4 )alkoxy, wherein said (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy are optionally substituted with 1 to 3 halo;

R 7 is hydrogen or —CH 2 OH; and

R 9 is —NH(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkyl substituted with OH.

2. The compound of claim 1 , wherein the compound is of the Formula VIII:

or a pharmaceutically acceptable salt thereof, wherein Z is a 5- or 6-membered heterocyclyl ring having one or more heteroatoms selected from oxygen or nitrogen; and wherein Z is optionally substituted with (C 1 -C 4 )alkyl or 1 to 3 halo.

3. The compound of claim 2 , wherein the compound is of the Formula XI:

or a pharmaceutically acceptable salt thereof, wherein R 10 and R 11 are each independently hydrogen or halo.

4. The compound of claim 3 , wherein R 1 is halo(C 1 -C 4 )alkyl, cyclopropyl, or cyclobutyl, wherein said cyclopropyl and cyclobutyl are each optionally substituted with 1 to 3 halo.

5. The compound of claim 3 , wherein L 2 is CH 2 .

6. The compound of claim 3 , wherein R 7 is —CH 2 OH; and A is N.

7. The compound of claim 3 , wherein R 10 and R 11 are each fluoro.

8. The compound of claim 3 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

9. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 3 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 3 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

12. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

13. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

14. A compound selected from:

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(methylsulfonyl)phenyl)acetamide;

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-((2-hydroxyethyl)sulfonyl)phenyl)acetamide;

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-((2-methoxyethyl)sulfonyl)phenyl)acetamide;

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(N-methylsulfamoyl)phenyl)acetamide;

2-(4-cyanophenyl)-N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)acetamide;

ethyl 2-(4-(2-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)amino)-2-oxoethyl)phenyl)acetate;

2-(4-(2-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)amino)-2-oxoethyl)phenyl)acetic acid;

N-(2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide;

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(1-(methylsulfonyl)piperidin-4-yl)acetamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1,1-difluoroethyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N—((R)-1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-((R)-tetrahydrofuran-2-yl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-ethyl-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(1-fluorocyclobutyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(2-hydroxy-1-(4-(methylsulfonyl)phenyl)ethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(methoxymethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-ethyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

2-(tert-butyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-isopropyl-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-methyl-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-isobutyl-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(N-methylsulfamoyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1,1-difluoroethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-(4-(N-methylsulfamoyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-fluorocyclobutyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(N-methylsulfamoyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-((2-hydroxyethyl)sulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(methylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-methoxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(1-methoxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-sulfamoylbenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(propylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

methyl 2-((4-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)phenyl)sulfonyl)acetate;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(2-methoxypropan-2-yl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-methoxy-1H-benzo[d]imidazole-5-carboxamide;

2-((1S,2R)-2-cyanocyclopropyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

2-((1R,2R)-2-cyanocyclopropyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

methyl (1R,2R)-2-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-5-((4-(ethylsulfonyl)benzyl)carbamoyl)-1H-benzo[d]imidazol-2-yl)cyclopropane-1-carboxylate;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-methoxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-methoxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-methoxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-methoxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1,1-difluoroethyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-((5-(methylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(ethylsulfonyl)pyridin-2-yl)methyl)-2-(1-fluorocyclobutyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((5-(methylsulfonyl)pyridin-2-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-(methylsulfonyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-(methylsulfonyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(1-fluorocyclopropyl)-N-((1-(methylsulfonyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

methyl 2-((4-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)piperidin-1-yl)sulfonyl)acetate;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-((2-(methylamino)-2-oxoethyl)sulfonyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

methyl 2-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)-2-(1-(methylsulfonyl)piperidin-4-yl)acetate;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-(N-methylsulfamoyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-((1-((2-amino-2-oxoethyl)sulfonyl)piperidin-4-yl)methyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-((2-(methylamino)-2-oxoethyl)sulfonyl)piperidin-4-yl)methyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,3-dihydrobenzofuran-7-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-(benzo[d][1,3]dioxol-4-ylmethyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((2-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((2-oxo-1,2-dihydroquinolin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-(benzofuran-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,3-dihydrobenzofuran-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((1H-indazol-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-(benzo[d][1,3]dioxol-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((1H-pyrrolo[2,3-c]pyridin-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-((2,3-dihydrobenzofuran-7-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-2-cyclopropyl-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

2-(4-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)cyclohexyl)acetic acid;

N-((1H-benzo[d][1,2,3]triazol-6-yl)methyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)—N-(1-(4-cyanophenyl)-2-hydroxyethyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)-2-fluorophenyl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-2-ethyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-2-ethyl-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-(ethylsulfonyl)-2-hydroxybenzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

methyl 2-((4-((1-((1H-indazol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)piperidin-1-yl)sulfonyl)acetate;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((4-oxo-1,4-dihydroquinolin-7-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(difluoromethyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-2-cyclobutyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-2-cyclopropyl-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(5-(ethylsulfonyl)pyridin-2-yl)-2-hydroxyethyl)-2-(1-fluorocyclopropyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(5-(methylsulfonyl)pyridin-2-yl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((1-methyl-1H-indazol-7-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((2-methyl-2H-indazol-7-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((1,2-dimethyl-1H-benzo[d]imidazol-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((1-methyl-1H-indazol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((1H-indazol-7-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(4-(ethylsulfonyl)benzyl)-1-((2-methyl-2H-indazol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-(benzo[d]oxazol-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-cyclopropyl-1-((2,3-dihydrobenzo[b][1,4]dioxin-5-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-2-cyclopropyl-1-(1-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)ethyl)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-(benzo[c][1,2,5]oxadiazol-4-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-(benzo[d]oxazol-7-ylmethyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

2-((1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)methyl)-5-(ethylsulfonyl)pyridine 1-oxide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(dimethylamino)-N-(4-(ethylsulfonyl)benzyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((1-((2-hydroxyethyl)sulfonyl)piperidin-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(1-(methylsulfonyl)piperidin-4-yl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-hydroxy-1-(1-(methylsulfonyl)piperidin-4-yl)ethyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-3-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)-3-(4-(ethylsulfonyl)phenyl)propanoic acid;

(R)-2-(2-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamido)-2-(4-(ethylsulfonyl)phenyl)ethoxy)acetic acid;

(S)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(1-(4-(ethylsulfonyl)phenyl)-3-(methylamino)-3-oxopropyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

(S)—N-(3-amino-1-(4-(ethylsulfonyl)phenyl)-3-oxopropyl)-1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(4-((2-(methylamino)-2-oxoethyl)sulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)-2-hydroxyacetamide;

(R)—N-(1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-2-(4-(ethylsulfonyl)phenyl)-2-hydroxyacetamide;

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-((4-methyl-1-(methylsulfonyl)-1,4-diazepan-5-yl)methyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

1-((2,3-dihydrobenzofuran-4-yl)methyl)-N-(4-(ethylsulfonyl)benzyl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

methyl 1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-5-((4-(ethylsulfonyl)benzyl)carbamoyl)-1H-benzo[d]imidazole-2-carboxylate; and

1-((2,2-difluorobenzo[d][1,3]dioxol-4-yl)methyl)-N-(2-(4-(ethylsulfonyl)phenyl)-1,3-dihydroxypropan-2-yl)-2-(trifluoromethyl)-1H-benzo[d]imidazole-5-carboxamide;

or a pharmaceutically acceptable salt of any of the foregoing.

15. A composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

16. A composition comprising the compound of claim 8 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

17. A composition comprising the compound of claim 9 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

18. A composition comprising the compound of claim 10 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

19. A composition comprising the compound of claim 11 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

20. A composition comprising the compound of claim 12 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

21. A composition comprising the compound of claim 13 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

22. A composition comprising the compound of claim 14 , 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 Nov 13, 2018

From: CLAREMON, DAVID A.; DILLARD, LAWRENCE WAYNE; FAN, YI; LOTESTA, STEPHEN D.; SINGH, SURESH B.; TICE, COLIN M.; ZHAO, WEI; ZHUANG, LINGHANG

To: VITAE PHARMACEUTICALS, INC.

Reel/Frame 047482/0037 →

Continuity (3)

Provisional Application 62320893 · Apr 11, 2016

Provisional Application 62288487 · Jan 29, 2016

Related Publication 20190352286A1 · Nov 21, 2019