IP Library › Granted Patent US 11,299,479

Granted Patent B1

US 11,299,479 · App. 17/068,518 · Granted Apr 12, 2022

Bisamide sarcomere activating compounds and uses thereof

Inventors: Luke Ashcraft (San Francisco, CA); Alessandro Boezio (Somerville, MA); John Butler (Somerville, MA); Aroop Chandra (South San Francisco, CA); Chihyuan Chuang (Millbrae, CA); Scott E. Collibee (San Carlos, CA); Mikkel V. Debenedetto (Shrewsbury, MA); Vincent DiMassa (South San Francisco, CA); Russell Graceffa (Hampton, NH); Justin Malinowski (Charlestown, MA); David Moebius (Westwood, MA); Bradley Paul Morgan (Moraga, CA); Joshua Payette (Santa Clara, CA); Antonio Romero (San Mateo, CA); David St. Jean, Jr. (Natick, MA); Richard Vargas (Bedford, MA); John Yeoman (Medford, MA); Hanmo Zhang (Chestnut Hill, MA); Alan Cheng (San Francisco, CA); Felix Gonzalez Lopez De Turiso (Cambridge, MA); Michael Garrett Johnson (San Francisco, CA)

Assignees: CYTOKINETICS, INC.; AMGEN INC.

C07D403/12 A61P9/00 C07D207/16 C07D209/02 C07D209/52 C07D401/06 C07D401/12 C07D401/14 C07D403/14 C07D405/12 C07D413/12 C07D413/14 C07D417/14

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Quick Facts

Patent No.: US 11,299,479
App. No.: 17/068,518
Granted: Apr 12, 2022
Kind: B1

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Abstract

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.

Claims (574)

1. A method of treating heart disease in a mammal comprising administering to the mammal a therapeutically effective amount of at least one compound, or pharmaceutically acceptable salt thereof, according to Formula (I):

wherein

Q is

X 1 is CR 2 ;

X 2 , X 4 and X 5 are each independently CR 3 ;

X 3 is CR 3a ;

R 1a is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and halogen;

R 1 is selected from the group consisting of C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl optionally substituted with 1 or 2 groups selected from hydroxy, halogen, and C 1 -C 4 alkyl, hydroxy C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, hydroxy C 3 -C 7 cycloalkylC 1 -C 4 alkyl, and 4 to 7 member heterocycloalkyl having 1 or 2 ring heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with 1 or 2 groups selected from oxo, hydroxy, halogen, and C 1 -C 4 alkyl;

R 2 is selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkoxy, and SF 5 ;

R 1 and R 2 , taken in combination, form a divalent group selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —OCH 2 —, —CH 2 OCH 2 —, —OCH 2 CH 2 , —CH 2 N(H)CH 2 —, and —CH 2 N(C 1 -C 4 alkyl)CH 2 —, each of which is optionally substituted with C 1 -C 4 alkyl or hydroxyC 1 -C 4 alkyl and wherein the oxygen of —OCH 2 CH 2 — or —OCH 2 — is attached to the CR 2 carbon;

R 3 is independently selected at each occurrence from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkoxy, and SF 5 ;

R 3a is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkoxy, or SF 5 ;

Z 1 is N or CR 5 ;

Z 2 is N or CR 6 ;

Z 3 is N or CR 7 , wherein 0, 1, or 2 of Z 1 , Z 2 , and Z 3 can be N;

R 4 is hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, cyano, benzoyl, SO 2 —R 8 or 4 to 7 member heterocycloalkyl having a ring heteroatom selected from N, O, and S which heterocycloalkyl is substituted with 0, 1, or 2 groups independently selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C(O)C 1 -C 6 alkyl, and SO 2 —R 8 , and wherein when R 4 is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl, it is optionally substituted with one or two groups independently selected from hydroxy, cyano, CO 2 H, CO 2 C 1 -C 6 alkyl, and C(O)NH 2 ;

R 5 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy, amino, mono- or di-C 1 -C 6 alkylamino, C 3 -C 7 cycloalkylamino or —N(H)C(O)C 1 -C 4 alkyl, where each alkyl or cycloalkyl is optionally substituted with hydroxy;

R 6 is hydrogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or halogen;

R 7 is hydrogen, C 1 -C 6 alkyl, or SO 2 C 1 -C 6 alkyl;

R 8 is C 1 -C 6 alkyl, NR 8d R 8e , C 3 -C 7 cycloalkyl, haloC 1 -C 6 alkyl or benzyl, wherein each alkyl, cycloalkyl or haloalkyl is optionally substituted with hydroxy, CO 2 H, CO 2 C 1 -C 6 alkyl or C(O)NH 2 ; or

R 8 is a group of the formula:

wherein

p is 1 or 2;

R 8a is hydrogen, C 1 -C 6 alkyl, benzyl, or phenyl optionally substituted with C 1 -C 6 alkyl or halogen;

R 8b is hydrogen, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, cyano, amino, N(H)C(O)C 1 -C 6 alkyl, N(H)C(O)C 3 -C 7 cycloalkyl, N(H)C(O)haloC 1 -C 6 alkyl, CO 2 H, C(O)NH 2 , C(O)NH(C 1 -C 6 alkyl), C(O)N(C 1 -C 6 alkyl) 2 , C(O)C 1 -C 6 alkyl, C(O)haloC 1 -C 6 alkyl, SO 2 C 1 -C 6 alkyl, phenyl optionally substituted with halogen, C 1 -C 4 alkyl, or haloC 1 -C 4 alkyl, benzyl optionally substituted with halogen, phenoxy optionally substituted with halogen, 4 to 7 member heterocycloalkyl having 1 or 2 ring heteroatoms selected from N, O, and S, or 5 or 6 member heteroaryl having 1 ring heteroatom selected from N, O, or S and 0, 1, or 2 additional ring nitrogen atoms, which heteroaryl is optionally substituted with 1 or 2 C 1 -C 6 alkyl, and wherein the alkoxy is optionally substituted with halogen, phenyl or halogen-substituted phenyl;

R 8c is hydrogen, halogen, hydroxy or C 1 -C 6 alkyl; or

CR 8b R 8c , taken in combination, forms a spirocyclic 3 to 6 member carbocycle or a 4 to 6 member heterocycle having a ring heteroatom selected from N, O, and S, which spirocycle is optionally substituted with hydroxy, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl or C 1 -C 4 alkoxy;

R 8d is hydrogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, or 4 to 7 member heterocycloalkyl having 1 ring heteroatoms selected from N, O, and S and 0 or 1 additional ring nitrogen atoms, which heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from hydroxy, halogen, oxo, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 8e is hydrogen or C 1 -C 6 alkyl; or

NR 8d R 8e , taken in combination, forms a 4 to 7 member heterocycloalkyl optionally comprising an additional ring heteroatom selected from N, O, and S, which heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from hydroxy, halogen, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy and heteroaryl, which heteroaryl has 5 or 6 ring atoms and has one ring heteroatom selected from N, O, and S and 0 or 1 additional ring nitrogen atom, or

NR 8d R 8e , taken in combination, forms a 5 or 6 member heteroaryl optionally comprising 1 additional ring heteroatom selected from N, O, and S;

R 13a is hydrogen or C 1 -C 6 alkyl;

R 13 and R 14 , taken in combination with the interposed C and N atoms, form a saturated 5 member heterocycle which heterocycle further comprises 0 or 1 additional ring heteroatoms selected from N, O, and S, which heterocycle is optionally fused to a benzo ring or to a saturated carbocycle having 3 to 7 ring atoms, or which heterocycle is optionally taken together with a saturated carbocyle having 3 to 7 ring atoms to form a spirocyclic ring, and wherein the heterocycle is optionally substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxy, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 7 cycloalkyl, 0-C(O)pyridine substituted with C 1 -C 4 alkyl and haloC 1 -C 4 alkyl; and

R 15 is hydrogen or halogen;

with the proviso that

(1) when R 4 is halogen, trifluoromethyl, or cyano and R 6 is hydrogen or halogen, then R 2 is not hydrogen or R 1 is not methyl,

(2) when R 5 is C 1 -C 6 alkoxy, then R 4 is not hydrogen or halogen, and

(3) when R 4 is C 1 -C 6 alkoxy or C 1 -C 6 alkyl, then R 2 is not hydrogen.

2. The method of claim 1 , wherein

R 2 is hydrogen, halogen, C 1 -C 4 alkyl, cyclopropyl, haloC 1 -C 4 alkyl, C 1 -C 4 alkoxy, or haloC 1 -C 4 alkoxy; and

R 3 is independently selected at each occurrence from the group consisting of hydrogen, halogen, C 1 -C 4 alkyl, cyclopropyl, haloC 1 -C 4 alkyl, C 1 -C 4 alkoxy, and haloC 1 -C 4 alkoxy.

3. The method of claim 1 , wherein

R 2 is hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy;

X 2 is CH;

R 3a is C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, haloC 1 -C 6 alkoxy, or SF 5 ;

X 4 is CR 3 ;

R 3 is hydrogen or halogen; and

X 5 is CH.

4. The method of claim 1 , wherein

R 2 is hydrogen, halogen, methyl, ethyl, methoxy, or ethoxy;

X 2 and X 5 are each CH;

R 3a is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, or SF 5 ;

X 4 is CR 3 ; and

R 3 is hydrogen or halogen.

5. The method of claim 1 , wherein R 1 is selected from the group consisting of C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylmethyl, and 4 to 6 member heterocycloalkyl having a ring heteroatom selected from N and O, which heterocycloalkyl is optionally substituted with 1 or 2 groups selected from oxo, halogen, and hydroxy, and wherein the alkyl or cycloalkyl is optionally substituted with hydroxy.

6. The method of claim 1 , wherein R 1 is C 1 -C 4 alkyl, trifluoromethyl, C 3 -C 5 cycloalkyl, C 3 -C 5 cycloalkylmethyl, oxetanyl, tetrahydrofuryl, or azetidinyl, wherein each alkyl, cycloalkyl, oxetanyl, or azetidinyl is optionally substituted with hydroxy or halogen.

7. The method of claim 1 , wherein R 1 is methyl, isopropyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, oxetanyl, difluoromethyl, 1-hydroxycyclopropyl, 3-hydroxycyclobutyl, 3-hydroxy-3-methylcyclobutyl, 3-fluorooxetanyl, or oxopyrrolidinyl.

8. The method of claim 1 , wherein R 13a is hydrogen; and R 13 and R 14 , taken in combination with the interposed C and N atoms, form a saturated 5 member heterocycle, which heterocycle further comprises 0 or 1 additional ring heteroatoms selected from N, O, and S, wherein the heterocycle is optionally fused to a saturated carbocycle having 3 to 7 ring atoms, or which heterocycle is optionally taken together with a saturated carbocyle having 3 to 7 ring atoms to form a spirocyclic ring, and wherein the heterocycle is optionally substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxy, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, and C 3 -C 7 cycloalkyl.

9. The method of claim 1 , wherein R 13a is hydrogen; and R 13 and R 14 , taken in combination with the interposed C and N atoms, form a heterocyclic ring selected from the group consisting of pyrrolidine and thiazolidine, wherein the heterocyclic ring is optionally fused to a cyclopropyl ring and the heterocyclic ring is further optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen, hydroxy, methyl, hydroxymethyl, methoxy, and cyclopropyl.

10. The method of claim 1 , wherein R 13a is hydrogen; and R 13 and R 14 , taken in combination with the interposed C and N atoms, form a pyrrolidine ring, wherein the pyrrolidine ring is optionally fused to a cyclopropyl ring and the pyrrolidine ring is further optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen, hydroxy, methyl, hydroxymethyl, and cyclopropyl.

11. The method of claim 1 , wherein

Q is

Z 2 is N or CR 6 ; Z 3 is N or CR 7 , wherein 0 or 1 of Z 2 and Z 3 can be N;

R 4 is C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, SO 2 —R 8 , or 4 to 7 member heterocycloalkyl having a ring heteroatom selected from N, O and S which heterocycloalkyl is substituted with 0, 1 or 2 groups independently selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C(O)C 1 -C 6 alkyl, and SO 2 R 8 and wherein each alkyl or cycloalkyl is optionally substituted with hydroxy, cyano, CO 2 H, or C(O)NH 2 ;

R 5 is hydrogen, C 1 -C 4 alkyl, amino, mono- or di-C 1 -C 4 alkylamino, C 3 -C 6 cycloalkylamino, or —N(H)C(O)C 1 -C 4 alkyl, where each alkyl or cycloalkyl is optionally substituted with hydroxy;

R 6 is hydrogen, C 1 -C 4 alkyl, haloC 1 -C 6 alkyl, or halogen;

R 7 is hydrogen or C 1 -C 4 alkyl; and

R 8 is C 1 -C 6 alkyl, NR 8d R 8e , C 3 -C 7 cycloalkyl or haloC 1 -C 6 alkyl, wherein each alkyl, cycloalkyl or haloalkyl is optionally substituted with hydroxy, CO 2 H, CO 2 C 1 -C 6 alkyl, or C(O)NH 2 ; or

R 8 is a group of the formula:

p is 1 or 2;

R 8a is hydrogen, C 1 -C 6 alkyl or phenyl substituted with halogen;

R 8b is hydrogen, halogen, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 5 cycloalkyl, cyano, amino or SO 2 C 1 -C 6 alkyl;

R 8c is hydrogen, halogen, hydroxyl, or C 1 -C 6 alkyl; or

CR 8b R 8c , taken in combination, forms a spirocyclic 3 to 6 member carbocycle or a 4 to 6 member heterocycle having a ring heteratom selected from N, O, and S, which spirocycle is optionally substituted with hydroxy, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl or C 1 -C 4 alkoxy;

R 8d is hydrogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, or 4 to 7 member heterocycloalkyl having a ring heteroatoms selected from N, O and S and 0 or 1 additional ring nitrogen atoms, which heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from hydroxy, halogen, oxo, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 8e is hydrogen or C 1 -C 6 alkyl; or

NR 8d R 8e , taken in combination, forms a 4 to 7 member heterocycloalkyl optionally comprising 1 additional ring heteroatom selected from N, O and S, which heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from hydroxy, halogen, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy and heteroaryl, which heteroaryl has 5 or 6 ring atoms and has one ring heteroatom selected from N, O, and S and 0 or 1 additional ring nitrogen atom, or

NR 8d R 8e , taken in combination, forms a 5 or 6 member heteroaryl, which heteroaryl optionally comprises 1 additional ring heteroatom selected from N, O, and S.

12. The method of claim 1 , wherein

Q is

Z 2 is CH or N;

Z 3 is CH or N; and

R 8 is C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl or haloC 1 -C 6 alkyl; or

R 8 is a group of the formula:

R 8b is halogen, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 5 cycloalkyl, cyano, or amino;

R 8c is hydrogen, halogen, hydroxyl, or C 1 -C 6 alkyl; or

CR 8b R 8c , taken in combination, forms a spirocyclic 3 to 4 member carbocycle or a 4 or 5 member heterocycle having a ring heteroatom selected from N, O, and S, which spirocycle is optionally substituted with hydroxy, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, or C 1 -C 4 alkoxy.

13. The method of claim 1 , according to the formula:

wherein

R 1 is selected from the group consisting of C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylmethyl, and 4 to 6 member heterocycloalkyl having a ring heteroatom selected from N and O, which heterocycloalkyl is optionally substituted with 1 or 2 groups selected from oxo or hydroxy, and wherein the alkyl or cycloalkyl is optionally substituted with hydroxy;

R 2 is hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy;

R 3a is C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, or SF 5 ;

X 4 is CR 3 ;

R 3 is hydrogen or halogen;

Z 2 is CH or N;

Z 3 is CH or N;

R 8 is C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl or haloC 1 -C 6 alkyl; or

R 8 is a group of the formula:

R 8b is halogen, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 5 cycloalkyl, cyano, or amino;

R 8c is hydrogen, halogen, hydroxy or C 1 -C 6 alkyl; or

W is CH 2 ; and

R 15a and R 15b are independently selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 4 alkyl, hydroxyC 1 -C 4 alkyl, C 1 -C 4 alkoxy, and C 3 -C 6 cycloalkyl; or

R 15a and R 15b , taken in combination with the carbon atom to which they are attached, form a spirocyclic cyclopropyl ring; and

R 16 is hydrogen; or

R 15a and R 16 , taken in combination with the carbon atoms to which they are attached, form a fused cyclopropyl ring.

14. The method of claim 13 , wherein

X 4 is CR 3 ;

R 3 is hydrogen or halogen;

W is CH 2 ;

Z 2 is N; and

Z 3 is CH.

15. A method of treating heart disease in a mammal comprising administering to the mammal a therapeutically effective amount of at least one compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-2-cyclopropyl-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-4,4-difluoro-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-3,3,3-trifluoro-1-(4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-2-methylpropyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

(1-((3-((3-cyano-1-azetidinyl)sulfonyl)-5-fluorophenyl)carbonyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)-2-(2-(ethylamino)-5-methylbenzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N-((1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-D-prolinamide;

1-(2-(cyclopropylamino)-5-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N—((R)-cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1S)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(4R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-1-(2-(ethylamino)-5-methylbenzoyl)-4-hydroxy-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N—((S)-cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)-2-(2-(cyclobutylamino)-5-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

1-(2-(cyclobutylamino)-5-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-3-methyl-1-(4-(trifluoromethyl)phenyl)butyl)-D-prolinamide;

1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-N-((1R)-1-(2-fluoro-4-methylphenyl)ethyl)-D-prolinamide;

1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-N-((1R)-1-(4-(difluoromethyl)-2-fluorophenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-(ethylamino)-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N—((R)-cyclopropyl(4-(pentafluoro-lambda˜6˜-sulfanyl)phenyl)methyl)-D-prolinamide;

N-((1S)-1-(4-chlorophenyl)-2-hydroxyethyl)-1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(5-(methylsulfonyl)-2-(2-propanylamino)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N-((1R)-1-(4-chlorophenyl)ethyl)-1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-(ethylamino)-5-(methylsulfonyl)benzoyl)-D-prolinamide;

methyl ((3-(((1R,3R,5R)-3-(((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)carbamoyl)-2-azabicyclo[3.1.0]hexan-2-yl)carbonyl)phenyl)sulfonyl)acetate;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(5-(methylsulfonyl)-2-(2-propanylamino)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-(3-fluoro-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1S)-1-(4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-(cyclopropylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-(3-((2-hydroxyethyl)sulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-((2-methyl-2-propanyl)amino)-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N-((1R)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-(ethylamino)-5-methylbenzoyl)-D-prolinamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-1-(2-(ethylamino)-5-methylbenzoyl)-4-hydroxy-D-prolinamide;

N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-((2-hydroxyethyl)sulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(N—((R)-(4-chloro-3-fluorophenyl)(cyclopropyl)methyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(trifluoromethyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-((2-hydroxyethyl)amino)-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-N-((1R)-1-(4-(difluoromethyl)phenyl)ethyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-1-(3,5-difluorophenyl)propyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-(trifluoromethyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(3-(ethylsulfonyl)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(3-(methylsulfonyl)benzoyl)-1,3-thiazolidine-4-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-(ethylsulfonyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-(cyclopropylsulfonyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-sulfamoylbenzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-(3-methyl-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(3-(dimethylsulfamoyl)benzoyl)-N-((1R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-(methylamino)-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-((2-hydroxyethyl)amino)-5-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1S)-2-hydroxy-1-(3-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((5-(ethylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclobutyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((5-(cyclopropylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1S)-1-(3,5-difluorophenyl)propyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(4-(difluoromethyl)-2,5-difluorophenyl)methyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-(3-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(3-(1-carbamoylcyclopropyl)benzoyl)-N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(dimethylsulfamoyl)benzoyl)-N-((1R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-2-methylpropyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-((2-methyl-2-propanyl)amino)-5-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(3-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(4-(difluoromethyl)-2,5-difluorophenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-(methylsulfonyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1S)-1-(2-fluoro-4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-1-(3,5-difluorophenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2-fluorophenyl)(3-oxetanyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(cyclopropylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(ethylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-(3-(2-methyl-2-propanyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-1-((6-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)-2-(2-(ethylamino)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(3-fluoro-5-(methylsulfonyl)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1S)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-2-methylpropyl)-D-prolinamide;

N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-1-((4-(methylsulfonyl)-2-pyridinyl)carbonyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(cyclopropylsulfonyl)benzoyl)-D-prolinamide;

N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-1-(3-sulfamoylbenzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-(methylamino)-5-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-((5-(cyclobutylamino)-2-methyl-4-pyridinyl)carbonyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((4-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclobutyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(3S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-3-(trifluoromethyl)-L-prolinamide;

(3R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-3-(trifluoromethyl)-D-prolinamide;

(3S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-3-(trifluoromethyl)-L-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)((3R)-5-oxo-3-pyrrolidinyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(1-(cyclopropylsulfonyl)-3-fluoro-3-azetidinyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-((2-hydroxyethyl)sulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(trifluoromethyl)benzoyl)-D-prolinamide;

N—((R)-(4-chloro-3-fluorophenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

N-((1R)-1-(4-chloro-3-fluorophenyl)propyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-fluoro-1-((6-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(1-amino-2-methyl-1-oxo-2-propanyl)benzoyl)-N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-3-fluorophenyl)(3-oxetanyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((2-(difluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-fluoro-1-((4-(methylsulfonyl)-2-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)-4-fluoro-N—((R)-(3-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(ethylsulfonyl)benzoyl)-N—((R)-3-oxetanyl(4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-3,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-fluoro-1-(3-sulfamoylbenzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-((2,2,2-trifluoroethyl)sulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(3-fluoro-1-(methylsulfonyl)-3-azetidinyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((4-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-methyl-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((2-(cyclopropylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-(4-chloro-2-fluorophenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

N-((1R)-1-(4-chlorophenyl)-2-hydroxyethyl)-1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-D-prolinamide;

((3-(((1R,3R,5R)-3-(((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)carbamoyl)-2-azabicyclo[3.1.0]hexan-2-yl)carbonyl)phenyl)sulfonyl)acetic acid;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-methoxy-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(cyclopropylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((S)-(4-chloro-2,5-difluorophenyl)(1-hydroxycyclopropyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4,4-difluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-(3-methyl-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N-((1S)-1-(4-chlorophenyl)ethyl)-1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-D-prolinamide;

(1R,2R,5S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-3-(3-sulfamoylbenzoyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-1,3-thiazolidine-4-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2-fluorophenyl)(cyclopropyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(2-amino-5-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(1-carbamoylcyclopropyl)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-(2-(2,2,2-trifluoroacetamido)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-(4-chloro-2-fluorophenyl)(3-oxetanyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-(difluoromethyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)pyrrolidine-2-carboxamide;

(4S)—N—((R)-(4-chloro-3-fluorophenyl)(3-oxetanyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-(3-cyanobenzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-cyclopropylbenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

1-(3-(methylsulfonyl)benzoyl)-N—((R)-3-oxetanyl(4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)-2-(2-acetamidobenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(3-(methylsulfonyl)benzoyl)-N—((R)-3-oxetanyl(4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-chlorobenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(ethylsulfonyl)benzoyl)-N—((S)-(2-fluoro-4-(trifluoromethyl)phenyl)(1-hydroxycyclopropyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(ethylamino)-2-methyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-2-hydroxy-1-(3-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((2-(ethylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,2R,5S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-3-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide;

(1R,3R,5R)—N-((1S,2S)-1-(4-chloro-2,5-difluorophenyl)-2-hydroxypropyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-hydroxy-1-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-D-prolinamide;

(4R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-4-hydroxy-1-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-D-prolinamide;

(2R,4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)pyrrolidine-2-carboxamide;

(1R,3R,5R)—N—((R)-(4-chlorophenyl)(3-oxetanyl)methyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N-((1S,2S)-1-(4-chloro-2,5-difluorophenyl)-2-hydroxypropyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,2R,5S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(3-(methylsulfonyl)benzoyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide;

N—((S)-(4-chloro-3-fluorophenyl)(cyclopropyl)methyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((4-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)-1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-4-fluoro-N-((1R)-1-(3-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(2-cyano-2-propanyl)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(2-propanyl)benzoyl)-D-prolinamide;

(4S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-D-prolinamide;

N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-1-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(3-fluoro-1-(methylsulfonyl)-3-azetidinyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-(4-chloro-3-fluorophenyl)(cyclopropyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(4S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

1-((3-(5-azaspiro[2.3]hex-5-ylsulfonyl)phenyl)carbonyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

1-(3-(dimethylsulfamoyl)benzoyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(4-(methylsulfonyl)picolinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4,4-difluoro-1-(3-sulfamoylbenzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(3-fluoro-1-(3-oxetanylsulfonyl)-3-azetidinyl)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(1-cyanocyclopropyl)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-((5-(cyclopropylamino)-2-methyl-4-pyridinyl)carbonyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-fluoro-5-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(3-((3-hydroxy-3-methyl-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((4-cyclopropyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-(4-methyl-3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(3R,5R)-5-(((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)carbamoyl)-1-((2-(difluoromethyl)-4-pyridinyl)carbonyl)-3-pyrrolidinyl 2-(difluoromethyl)-4-pyridinecarboxylate;

N—((R)-(4-chloro-2-fluorophenyl)(cyclopropyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-((2-(difluoromethyl)-4-pyridinyl)carbonyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(methylsulfonyl)benzoyl)-N—((R)-((3R)-5-oxo-3-pyrrolidinyl)(4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1S,2R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-(3-(methylsulfonyl)benzoyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-3-fluorophenyl)(cyclopropyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((6-(trifluoromethyl)-4-pyrimidinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-fluoro-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((6-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(cyclopropylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(3R,5R)-5-(((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)carbamoyl)-1-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-3-pyrrolidinyl 2-(trifluoromethyl)-4-pyridinecarboxylate;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(3-(1-amino-2-methyl-1-oxo-2-propanyl)benzoyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((2-(trifluoromethyl)-4-pyrimidinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-1-((2-(difluoromethyl)-4-pyridinyl)carbonyl)-4-hydroxy-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((2-(2-propanyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((6-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-hydroxy-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-fluoro-1-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-D-prolinamide;

(1R,2R,5S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-3-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide;

(1R,3R,5R)—N-((1R)-1-(4-chloro-2,5-difluorophenyl)ethyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((S)-(2-fluoro-4-(trifluoromethyl)phenyl)((3R)-1-methyl-5-oxo-3-pyrrolidinyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-(ethylamino)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-(3-(ethylsulfonyl)benzoyl)-N—((S)-(1-hydroxycyclobutyl)(4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(2,2,2-trifluoro-1,1-dihydroxyethyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((4-(methylsulfonyl)-2-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)-4-fluoro-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((6-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-cyclobutylbenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-(3-sulfamoylbenzoyl)-D-prolinamide;

1-(3-(1-carbamoylcyclopropyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)—N-((1R)-1-(4-chloro-2,5-difluorophenyl)ethyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((5-((2-hydroxyethyl)amino)-2-methyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-((2-hydroxyethyl)amino)-2-methyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-N—((R)-3-oxetanyl(4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-((1R)-2,2,2-trifluoro-1-hydroxyethyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-((1S)-2,2,2-trifluoro-1-hydroxyethyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(2-(3-cyano-1-azetidinyl)-5-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-(2,2,2-trifluoroacetamido)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-ethoxy-5-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((4-ethyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-((1R)-2,2,2-trifluoro-1-hydroxyethyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-((1S)-2,2,2-trifluoro-1-hydroxyethyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((S)-(2-fluoro-4-(trifluoromethyl)phenyl)(1-hydroxycyclopropyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2,6-difluoro-3-(methylsulfonyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-fluoro-5-sulfamoylbenzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-2-thiophenyl)carbonyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((6-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

N—((S)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((6-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-cyano-2,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,2R,5S)-3-(3-(dimethylsulfamoyl)benzoyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-3-azabicyclo[3.1.0]hexane-2-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((4-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)((3R)-1-methyl-5-oxo-3-pyrrolidinyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(3-fluoro-3-oxetanyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(dimethylamino)benzoyl)-D-prolinamide;

(5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-5-methyl-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(3R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-3-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((4-cyclopropyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-((3-(5-azaspiro[2.3]hex-5-ylsulfonyl)phenyl)carbonyl)-N-((1R)-1-(4-chlorophenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1S,3R,5S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-(3-(3-fluoro-3-oxetanyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((4-methyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N-((1S,2S)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-2-hydroxypropyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-methoxy-5-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((2,6-dimethyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(1-cyanocyclopropyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(difluoromethyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(3-benzoylbenzoyl)-N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-((5-cyclopropyl-3-pyridinyl)carbonyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-methoxy-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((6-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-5-methyl-1-(3-(methylsulfonyl)benzoyl)-L-prolinamide;

(1R,3R,5R)—N-(4-chloro-2,5-difluorobenzyl)-2-(3-(ethylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((2-methyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-methyl-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(3-((3-cyano-1-azetidinyl)sulfonyl)benzoyl)-N-((1R)-2,2-dimethyl-1-(4-(trifluoromethyl)phenyl)propyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-3-fluorophenyl)(cyclopropyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N-((1S)-1-(4-chloro-3-fluorophenyl)propyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

N-((1R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)propyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

N-((1S)-1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

1-((3-(5-azaspiro[2.3]hex-5-ylsulfonyl)phenyl)carbonyl)-N-((1R)-1-(3,4-dichlorophenyl)ethyl)-D-prolinamide;

N-((1R)-1-(4-chloro-2,5-difluorophenyl)ethyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-4-hydroxy-1-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-ethyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-4-hydroxy-1-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((2-(2-methyl-2-propanyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(methoxy(methyl)sulfamoyl)benzoyl)-N-(4-(trifluoromethyl)benzyl)-D-prolinamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-(difluoromethyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((4-methyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((4-ethyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-methyl-5-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((6-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((S)-(3-fluoro-3-oxetanyl)(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((S)-(3-fluoro-3-oxetanyl)(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(dimethylsulfamoyl)benzoyl)-N-((1S)-2-hydroxy-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(trifluoromethyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-4-(difluoromethyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((S)-(2-fluoro-4-(trifluoromethyl)phenyl)((3S)-5-oxo-3-pyrrolidinyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(cyclopropylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(2-chloro-5-sulfamoylbenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(4-fluoro-3-(methylsulfonyl)benzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(3-methyl-3-oxetanyl)benzoyl)-D-prolinamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-methyl-3-(3-(methylsulfonyl)benzoyl)-2-oxo-4-imidazolidinecarboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-2-((5-methyl-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(4R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-methyl-3-(3-(methylsulfonyl)benzoyl)-2-oxo-4-imidazolidinecarboxamide;

(4S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-methyl-3-(3-(methylsulfonyl)benzoyl)-2-oxo-4-imidazolidinecarboxamide;

1-(3-cyanobenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-methyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(1-(methylsulfonyl)-3-azetidinyl)benzoyl)-D-prolinamide;

(4S)-4-fluoro-N—((S)-(3-fluoro-3-oxetanyl)(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((4-cyclopropyl-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-methylbenzoyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(2-methyl-5-sulfamoylbenzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-methyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-((4-cyclopropyl-2-pyridinyl)carbonyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(4-(difluoromethyl)-2-fluorophenyl)methyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(4S)—N—((R)-(4-chloro-2,5-difluorophenyl)(3-oxetanyl)methyl)-4-hydroxy-1-((2-(trifluoromethyl)-4-pyridinyl)carbonyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(3-thiophenyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-(4-methyl-3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,4-difluorophenyl)(3-oxetanyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1S,3R,5S)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((2-methyl-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(1H-pyrazol-4-yl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-2-fluorophenyl)(3-oxetanyl)methyl)-2-((2-(2-methyl-2-propanyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(1H-pyrazol-3-yl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-methoxyphenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((2-(2-propanyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(methyl(2-propyn-1-yl)sulfamoyl)benzoyl)-N-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-D-prolinamide;

(1R,5R)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-1-carboxamide;

(1R,3R,5R)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-(3-(S-methylsulfonimidoyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(2-aminobenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(3R)—N—((R)-cyclopropyl(4-(trifluoromethyl)phenyl)methyl)-3-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N-((1S,2R)-1-(4-chloro-2,5-difluorophenyl)-2-hydroxypropyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-D-prolinamide;

N—((S)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-D-prolinamide;

(1S,3R,5S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

methyl N-((3-(((2R)-2-((4-(trifluoromethyl)benzyl)carbamoyl)-1-pyrrolidinyl)carbonyl)phenyl)sulfonyl)glycinate;

N-((1R)-1-(4-chloro-3-fluorophenyl)propyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(2-chloro-4-fluoro-5-sulfamoylbenzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1S,3R,5S)—N—((R)-(4-chloro-2,5-difluorophenyl)(cyclopropyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-methoxybenzoyl)-D-prolinamide;

1-((3-((3-cyano-1-azetidinyl)sulfonyl)phenyl)carbonyl)-N-((1R)-1-phenylethyl)-D-prolinamide;

(1R,3R,5R)-2-((4-ethyl-2-pyridinyl)carbonyl)-N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2-fluoro-4-(trifluoromethyl)phenyl)(3-oxetanyl)methyl)-2-((6-(trifluoromethyl)-2-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(5S)—N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-5-methyl-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(4S)—N—((R)-cyclopropyl(3-fluoro-4-methylphenyl)methyl)-4-fluoro-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

1-(3-(ethylsulfonyl)benzoyl)-N-(4-(trifluoromethyl)benzyl)-D-prolinamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(2-hydroxy-2-propanyl)benzoyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-(4-chloro-3-fluorophenyl)(cyclopropyl)methyl)-2-((2-(methylsulfonyl)-4-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

1-(3-(1-acetyl-3-fluoro-3-azetidinyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-methyl-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((S)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-(3-(dimethylsulfamoyl)benzoyl)-D-prolinamide;

1-(4-amino-3-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-D-prolinamide;

N-((1R)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-2-methylpropyl)-1-(3-(methylsulfonyl)benzoyl)-D-prolinamide;

(1R,3R,5R)-2-(2-methoxy-5-(methylsulfonyl)benzoyl)-N—((R)-3-oxetanyl(4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

N—((S)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-1-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-D-prolinamide;

(1R,3R,5R)—N—((R)-cyclopropyl(3-fluoro-4-methylphenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((S)-(4-chloro-2,5-difluorophenyl)(3-fluorooxetan-3-yl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(2-amino-5-(methylsulfonyl)benzoyl)-N—((R)-cyclopropyl(2-fluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-(2-(hydroxymethyl)-5-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)(oxetan-3-yl)methyl)-2-(2-methoxyisonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)(oxetan-3-yl)methyl)-2-(5-methylthiophene-2-carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((S)-1-(4-chloro-2,5-difluorophenyl)-2,2-difluoroethyl)-2-(5-(methylsulfonyl)nicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)(oxetan-3-yl)methyl)-2-(3-(2-hydroxypropan-2-yl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)(oxetan-3-yl)methyl)-2-(5-methyl-1H-indazole-7-carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)-2-(5-chloro-1H-indazole-7-carbonyl)-N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-(5-(1-hydroxyethyl)-2-methylisonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)((1s,3S)-3-hydroxycyclobutyl)methyl)-1-(3-(methylsulfonyl)benzoyl)pyrrolidine-2-carboxamide;

(R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)((1r,3R)-3-hydroxycyclobutyl)methyl)-1-(3-(methylsulfonyl)benzoyl)pyrrolidine-2-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)((1r,3R)-3-hydroxy-3-methylcyclobutyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)((1s,3S)-3-hydroxycyclobutyl)methyl)-2-(2-(difluoromethyl)isonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((R)-(2,5-difluoro-4-(trifluoromethyl)phenyl)((1r,3R)-3-hydroxycyclobutyl)methyl)-2-(2-(difluoromethyl)isonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide;

(1R,3R,5R)—N—((S)-(2,5-difluoro-4-(trifluoromethyl)phenyl)((R)-5-oxopyrrolidin-3-yl)methyl)-2-(2-(trifluoromethyl)isonicotinoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide; and

(1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethoxy)phenyl)methyl)-2-(3-(methylsulfonyl)benzoyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide.

16. The method of claim 1 , wherein the at least one compound is (1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide or a pharmaceutically acceptable salt thereof.

17. A method of modulating the cardiac sarcomere in a mammal comprising administering to the mammal a therapeutically effective amount of at least one compound, or pharmaceutically acceptable salt thereof, according to Formula (I):

wherein

Q is

X 1 is CR 2 ;

X 2 , X 4 and X 5 are each independently CR 3 ;

X 3 is CR 3a ;

R 1a is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and halogen;

R 1 is selected from the group consisting of C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl optionally substituted with 1 or 2 groups selected from hydroxy, halogen, and C 1 -C 4 alkyl, hydroxy C 3 -C 7 cycloalkyl, C 3 C 7 cycloalkylC 1 -C 4 alkyl, hydroxy C 3 -C 7 cycloalkylC 1 -C 4 alkyl, and 4 to 7 member heterocycloalkyl having 1 or 2 ring heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with 1 or 2 groups selected from oxo, hydroxy, halogen, and C 1 -C 4 alkyl;

R 1 and R 2 , taken in combination, form a divalent group selected from —CH 2 , —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —OCH 2 —, —CH 2 OCH 2 —, —OCH 2 CH 2 , —CH 2 N(H)CH 2 —, and —CH 2 N(C 1 -C 4 alkyl)CH 2 —, each of which is optionally substituted with C 1 -C 4 alkyl or hydroxyC 1 -C 4 alkyl and wherein the oxygen of —OCH 2 CH 2 — or —OCH 2 — is attached to the CR 2 carbon;

R 3a is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkoxy, or SF 5 ;

Z 1 is N or CR 5 ;

Z 2 is N or CR 6 ;

Z 3 is N or CR 7 , wherein 0, 1, or 2 of Z 1 , Z 2 and Z 3 can be N;

R 6 is hydrogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or halogen;

R 7 is hydrogen, C 1 -C 6 alkyl, or SO 2 C 1 -C 6 alkyl;

R 8 is a group of the formula:

wherein

p is 1 or 2;

R 8a is hydrogen, C 1 -C 6 alkyl, benzyl, or phenyl optionally substituted with C 1 -C 6 alkyl, or halogen;

R 8b is hydrogen, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, cyano, amino, N(H)C(O)C 1 -C 6 alkyl, N(H)C(O)C 3 -C 7 cycloalkyl, N(H)C(O)haloC 1 -C 6 alkyl, CO 2 H, C(O)NH 2 , C(O)NH(C 1 -C 6 alkyl), C(O)N(C 1 -C 6 alkyl) 2 , C(O)C 1 -C 6 alkyl, C(O)haloC 1 -C 6 alkyl, SO 2 C 1 -C 6 alkyl, phenyl optionally substituted with halogen, C 1 -C 4 alkyl or haloC 1 -C 4 alkyl, benzyl optionally substituted with halogen, phenoxy optionally substituted with halogen, 4 to 7 member heterocycloalkyl having 1 or 2 ring heteroatoms selected from N, O and S, or 5 or 6 member heteroaryl having 1 ring heteroatom selected from N, O or S and 0, 1 or 2 additional ring nitrogen atoms, which heteroaryl is optionally substituted with 1 or 2 C 1 -C 6 alkyl, and wherein the alkoxy is optionally substituted with halogen, phenyl, or halogen-substituted phenyl;

R 8c is hydrogen, halogen, hydroxyl, or C 1 -C 6 alkyl; or

CR 8b R 8c , taken in combination, forms a spirocyclic 3 to 6 member carbocycle or a 4 to 6 member heterocycle having a ring heteroatom selected from N, O and S, which spirocycle is optionally substituted with hydroxy, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, or C 1 -C 4 alkoxy;

R 8d is hydrogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, or 4 to 7 member heterocycloalkyl having 1 ring heteroatoms selected from N, O and S and 0 or 1 additional ring nitrogen atoms, which heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from hydroxy, halogen, oxo, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;

R 8e is hydrogen or C 1 -C 6 alkyl; or

NR 8d R 8e , taken in combination, forms a 4 to 7 member heterocycloalkyl optionally comprising an additional ring heteroatom selected from N, O and S, which heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from hydroxy, halogen, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy and heteroaryl, which heteroaryl has 5 or 6 ring atoms and has one ring heteroatom selected from N, O, and S and 0 or 1 additional ring nitrogen atom, or

NR 8d R 8e , taken in combination, forms a 5 or 6 member heteroaryl optionally comprising 1 additional ring heteroatom selected from N, O, and S;

R 13a is hydrogen or C 1 -C 6 alkyl;

R 13 and R 14 , taken in combination with the interposed C and N atoms, form a saturated 5 member heterocycle which heterocycle further comprises 0 or 1 additional ring heteroatoms selected from N, O and S, which heterocycle is optionally fused to a benzo ring or to a saturated carbocycle having 3 to 7 ring atoms, or which heterocycle is optionally taken together with a saturated carbocyle having 3 to 7 ring atoms to form a spirocyclic ring, and wherein the heterocycle is optionally substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxy, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 7 cycloalkyl, 0-C(O)pyridine substituted with C 1 -C 4 alkyl, and haloC 1 -C 4 alkyl; and

R 15 is hydrogen or halogen;

with the proviso that

(1) when R 4 is halogen, trifluoromethyl, or cyano and R 6 is hydrogen or halogen, then R 2 is not hydrogen or R 1 is not methyl,

(2) when R 5 is C 1 -C 6 alkoxy, then R 4 is not hydrogen or halogen, and

(3) when R 4 is C 1 -C 6 alkoxy or C 1 -C 6 alkyl, then R 2 is not hydrogen,

to modulate the cardiac sarcomere in the mammal.

18. The method of claim 17 , wherein the at least one compound is (1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide or a pharmaceutically acceptable salt thereof.

19. A method for potentiating cardiac myosin in a mammal comprising administering to the mammal a therapeutically effective amount of at least one compound, or pharmaceutically acceptable salt thereof, according to Formula (I):

wherein

Q is R

X 1 is CR 2 ;

X 2 , X 4 and X 5 are each independently CR 3 ;

X 3 is CR 3a ;

R 1a is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, and halogen;

R 1 is selected from the group consisting of C 1 -C 6 alkyl, halo C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl optionally substituted with 1 or 2 groups selected from hydroxy, halogen, and C 1 -C 4 alkyl, hydroxy C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, hydroxy C 3 -C 7 cycloalkylC 1 -C 4 alkyl, and 4 to 7 member heterocycloalkyl having 1 or 2 ring heteroatoms independently selected from N, O and S, which heterocycloalkyl is optionally substituted with 1 or 2 groups selected from oxo, hydroxy, halogen, and C 1 -C 4 alkyl;

R 1 and R 2 , taken in combination, form a divalent group selected from —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —OCH 2 —, —CH 2 OCH 2 —, —OCH 2 CH 2 , —CH 2 N(H)CH 2 — and —CH 2 N(C 1 -C 4 alkyl)CH 2 —, each of which is optionally substituted with C 1 -C 4 alkyl or hydroxyC 1 -C 4 alkyl and wherein the oxygen of —OCH 2 CH 2 — or —OCH 2 — is attached to the CR 2 carbon;

R 3a is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 4 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkoxy, or SF 5

Z 1 is N or CR 5 ;

Z 2 is N or CR 6 ;

Z 3 is N or CR 7 , wherein 0, 1, or 2 of Z 1 , Z 2 , and Z 3 can be N;

R 4 is hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, cyano, benzoyl, SO 2 —R 8 or 4 to 7 member heterocycloalkyl having a ring heteroatom selected from N, O and S which heterocycloalkyl is substituted with 0, 1, or 2 groups independently selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C(O)C 1 -C 6 alkyl, and SO 2 —R 8 , and wherein when R 4 is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl, it is optionally substituted with one or two groups independently selected from hydroxy, cyano, CO 2 H, CO 2 C 1 -C 6 alkyl and C(O)NH 2 ;

R 6 is hydrogen, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or halogen;

R 7 is hydrogen, C 1 -C 6 alkyl, or SO 2 C 1 -C 6 alkyl;

R 8 is a group of the formula:

wherein

p is 1 or 2;

R 8a is hydrogen, C 1 -C 6 alkyl, benzyl, or phenyl optionally substituted with C 1 -C 6 alkyl or halogen;

R 8b is hydrogen, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, cyano, amino, N(H)C(O)C 1 -C 6 alkyl, N(H)C(O)C 3 -C 7 cycloalkyl, N(H)C(O)haloC 1 -C 6 alkyl, CO 2 H, C(O)NH 2 , C(O)NH(C 1 -C 6 alkyl), C(O)N(C 1 -C 6 alkyl) 2 , C(O)C 1 -C 6 alkyl, C(O)haloC 1 -C 6 alkyl, SO 2 C 1 -C 6 alkyl, phenyl optionally substituted with halogen, C 1 -C 4 alkyl or haloC 1 -C 4 alkyl, benzyl optionally substituted with halogen, phenoxy optionally substituted with halogen, 4 to 7 member heterocycloalkyl having 1 or 2 ring heteroatoms selected from N, O and S, or 5 or 6 member heteroaryl having 1 ring heteroatom selected from N, O or S and 0, 1 or 2 additional ring nitrogen atoms, which heteroaryl is optionally substituted with 1 or 2 C 1 -C 6 alkyl, and wherein the alkoxy is optionally substituted with halogen, phenyl or halogen-substituted phenyl;

R 8c is hydrogen, halogen, hydroxy or C 1 -C 6 alkyl; or

R 8e is hydrogen or C 1 -C 6 alkyl; or

NR 8d R 8e , taken in combination, forms a 5 or 6 member heteroaryl optionally comprising 1 additional ring heteroatom selected from N, O, and S;

R 13a is hydrogen or C 1 -C 6 alkyl;

R 13 and R 14 , taken in combination with the interposed C and N atoms, form a saturated 5 member heterocycle which heterocycle further comprises 0 or 1 additional ring heteroatoms selected from N, O and S, which heterocycle is optionally fused to a benzo ring or to a saturated carbocycle having 3 to 7 ring atoms, or which heterocycle is optionally taken together with a saturated carbocycle having 3 to 7 ring atoms to form a spirocyclic ring, and wherein the heterocycle is optionally substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxy, oxo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 7 cycloalkyl, 0-C(O)pyridine substituted with C 1 -C 4 alkyl and haloC 1 -C 4 alkyl; and

R 15 is hydrogen or halogen;

with the proviso that

(1) when R 4 is halogen, trifluoromethyl or cyano and R 6 is hydrogen or halogen, then R 2 is not hydrogen or R 1 is not methyl,

(2) when R 5 is C 1 -C 6 alkoxy, then R 4 is not hydrogen or halogen, and

(3) when R 4 is C 1 -C 6 alkoxy or C 1 -C 6 alkyl, then R 2 is not hydrogen,

to potentiate cardiac myosin in the mammal.

20. The method of claim 19 , wherein the at least one compound is (1R,3R,5R)—N—((R)-cyclopropyl(2,5-difluoro-4-(trifluoromethyl)phenyl)methyl)-2-((5-(methylsulfonyl)-3-pyridinyl)carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 , wherein R 4 is halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, cyano, benzoyl, SO 2 —R 8 or 4 to 7 member heterocycloalkyl having a ring heteroatom selected from N, O, and S which heterocycloalkyl is substituted with 0, 1, or 2 groups independently selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C(O)C 1 -C 6 alkyl, and SO 2 —R 8 , and wherein when R 4 is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl, it is optionally substituted with one or two groups independently selected from hydroxy, cyano, CO 2 H, CO 2 C 1 -C 6 alkyl, and C(O)NH 2 .

22. The method of claim 17 , wherein R 4 is halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, cyano, benzoyl, SO 2 —R 8 or 4 to 7 member heterocycloalkyl having a ring heteroatom selected from N, O, and S which heterocycloalkyl is substituted with 0, 1, or 2 groups independently selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C(O)C 1 -C 6 alkyl, and SO 2 —R 8 , and wherein when R 4 is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl, it is optionally substituted with one or two groups independently selected from hydroxy, cyano, CO 2 H, CO 2 C 1 -C 6 alkyl, and C(O)NH 2 .

23. The method of claim 19 , wherein R 4 is halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloC 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, cyano, benzoyl, SO 2 —R 8 or 4 to 7 member heterocycloalkyl having a ring heteroatom selected from N, O and S which heterocycloalkyl is substituted with 0, 1, or 2 groups independently selected from the group consisting of halogen, oxo, C 1 -C 6 alkyl, C(O)C 1 -C 6 alkyl, and SO 2 —R 8 , and wherein when R 4 is C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl, it is optionally substituted with one or two groups independently selected from hydroxy, cyano, CO 2 H, CO 2 C 1 -C 6 alkyl and C(O)NH 2 .

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 28, 2020

From: ASHCRAFT, LUKE; CHANDRA, AROOP; CHUANG, CHIHYUAN; COLLIBEE, SCOTT E.; DIMASSA, VINCENT; MORGAN, BRADLEY P.; ROMERO, ANTONIO

To: CYTOKINETICS, INC.

Reel/Frame 054755/0732 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 28, 2020

From: ST. JEAN, DAVID J., JR.; BUTLER, JOHN R.; DEBENEDETTO, MIKKEL V.; GRACEFFA, RUSSELL; MALINOWSKI, JUSTIN; MOEBIUS, DAVID C.; PAYETTE, JOSHUA; VARGAS, RICHARD; YEOMAN, JOHN; ZHANG, HANMO; BOEZIO, ALESSANDRO A.; CHENG, ALAN; GONZALEZ LOPEZ DE TURISO, FELIX; JOHNSON, MICHAEL GARRETT

To: AMGEN INC.

Reel/Frame 054755/0761 →

Continuity (3)

Division 16833336 · Mar 27, 2020

Division 16129862 · Sep 13, 2018

Provisional Application 62557846 · Sep 13, 2017

Cited By (5)

US 12,187,700 US 12,195,427 US 12,486,278 US 12,692,229 US 12,703,684