IP Library › Granted Patent US 12,209,088

Granted Patent B2

US 12,209,088 · App. 17/858,917 · Granted Jan 28, 2025

Hormone receptor modulators for treating metabolic conditions and disorders

Inventors: Jianhua Chao (Fremont, CA); Rakesh Jain (Fremont, CA); Lily Hu (Fremont, CA); Jason Gustaf Lewis (Fremont, CA); Helene Baribault (Fremont, CA); Jeremy Caldwell (Fremont, CA)

Assignee: ARDELYX, INC.

C07D471/08 C07D413/12 C07D413/14 C07D417/14 C07D493/08 C07F9/65583

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Quick Facts

Patent No.: US 12,209,088
App. No.: 17/858,917
Granted: Jan 28, 2025
Kind: B2

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Abstract

The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L 1 , A, X 1 , X 2 , R 1 , R 2 , and R 3 are described herein.

Claims (306)

1. A compound of Formula I:

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof;

wherein:

one of X 1 or X 2 is NR x and the other is CH 2 ;

R x is

L 1 is-(CH 2 ) m (C═O)— or —(CH 2 ) p —;

L 2 is a bond or —S(O) 2 —;

A is (C 3 -C 8 ) cycloalkyl, (C 6 -C 10 ) aryl, heterocycloalkyl, wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl, wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more R 7 ;

B is (C 6 -C 10 ) aryl that is optionally substituted with one or more R 5 ;

R 1 and R 2 are each independently H, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, (C 3 -C 7 ) cycloalkyl, or CN, wherein the cycloalkyl is optionally substituted with one or more R 9 ;

or R 1 and R 2 together when attached to the same carbon atom form a (C 3 -C 8 ) spirocycloalkyl ring optionally substituted with one or more R 8 ; or R 1 and R 2 together when attached to the same atom form a (C 3 -C 8 ) spiroheterocycloalkyl ring optionally substituted with one or more R 8 ; or R 1 and R 2 on adjacent atoms together with the atoms to which they are attached form a (C 3 -C 8 ) cycloalkyl ring optionally substituted with one or more R 8 ; or R 1 and R 2 on adjacent atoms together with the atoms to which they are attached form a heterocycloalkyl ring optionally substituted with one or more R 8 ; or R 1 and R 2 on adjacent atoms together with the atoms to which they are attached form a aryl ring optionally substituted with one or more R 8 ; or R 1 and R 2 on adjacent atoms together with the atoms to which they are attached form a heteroaryl ring optionally substituted with one or more R 8 ; or when A is cycloalkyl or heterocycloalkyl, R 1 and R 2 together with the atoms to which they are attached form a (C 3 -C 8 ) cycloalkyl ring optionally substituted with one or more R 8 ; or when cycloalkyl or heterocycloalkyl, R 1 and R 2 together with the atoms to which they are attached form a heterocycloalkyl ring optionally substituted with one or more R 8 ;

R 3 is (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, (C 1 -C 6 ) hydroxyalkyl, or (C 3 -C 7 ) cycloalkyl optionally substituted with one or more substituents each independently selected from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, and —OH;

R 4 is COOR 6a , CONR 6b R 6c , CONH(CH 2 ) n COOR 6a , CONR 6b SO 2 R 6d , CONH(CH 2 ) n SO 2 R 6e , CN, heterocycloalkyl wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S;

each R 5 is independently at each occurrence halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, CN, (C 3 -C 8 ) cycloalkyl, (C 6 -C 10 ) aryl, heterocycloalkyl wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and wherein the cycloalkyl, aryl, heterocycloalkyl or heteroaryl are optionally substituted with one or more substituents each independently selected from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, and (C 1 -C 6 ) haloalkoxy;

R 6a is H, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 3 -C 8 ) cycloalkyl, (C 6 -C 10 ) aryl, heterocycloalkyl wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, and —OH;

R 6b and R 6c are each independently H, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 3 -C 8 ) cycloalkyl, (C 6 -C 10 ) aryl, heterocycloalkyl wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, and —OH;

R 6d is (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 3 -C 8 ) cycloalkyl (C 6 -C 10 ) aryl, heterocycloalkyl wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, and —OH;

R 6e is-OH, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 3 -C 8 ) cycloalkyl, (C 6 -C 10 ) aryl, heterocycloalkyl wherein the heterocycloalkyl comprises one or two 5- to 7-membered rings and 1-4 heteroatoms selected from N, O and S, or heteroaryl wherein the heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S, and wherein the alkyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with one or more substituents each independently selected from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy, and —OH;

each R 7 is independently at each occurrence (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, or CN;

each R 8 is independently at each occurrence (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, or —OH;

each R 9 is independently at each occurrence (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, or —OH;

m is 0, 1, or 2;

n is 1 or 2; and

p is 1 or 2.

2. The compound of claim 1 , having one of the Formulae (Ia), or (Ib):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

3. The compound of claim 1 , having one of the Formulae (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii) or (Ij):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

4. The compound of claim 1 , having one of the Formulae (Ik), (II), (Im), or (In):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

5. The compound of claim 1 , wherein A is (C 6 -C 10 ) aryl.

6. The compound of claim 1 , wherein A is (C 6 -C 10 ) aryl optionally substituted with one or more R 7 .

7. The compound of claim 1 , wherein A is (C 3 -C 8 ) cycloalkyl.

8. The compound of claim 1 , wherein A is phenyl optionally substituted with one or more R 7 .

9. The compound of claim 1 , wherein A is cyclohexyl.

10. The compound of claim 1 , wherein R 1 and R 2 are each independently H, halogen, or (C 1 -C 6 ) haloalkyl.

11. The compound of claim 1 , wherein B is (C 6 -C 10 ) aryl optionally substituted with (C 1 -C 6 ) alkyl, halogen, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkoxy or CN.

12. The compound of claim 1 , wherein R 3 is (C 3 -C 7 ) cycloalkyl.

13. The compound of claim 1 , wherein R 3 is (C 3 -C 7 ) cycloalkyl substituted with halogen.

14. The compound of claim 1 , having one of the Formulae (Io), (Ip), (Iq), (Ir), (Is), or (It):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

15. The compound of claim 1 , having one of the Formulae (Iu) or (Iv):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

16. The compound of claim 1 , having one of the Formulae (ly) or (Iz):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

17. The compound of claim 1 , selected from the group consisting of:

4-[(1S,4S,5R)-5-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyloxy]-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4S,5R)-5-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyloxy]-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid;

4-[(1S,4S,5R)-5-[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazole-4-carbonyloxy]-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid;

(1S,4S,5R)-2-[4-(methanesulfonylcarbamoyl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

(1S,4S,5R)-2-{4-[(propane-1-sulfonyl) carbamoyl]phenyl}-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

(1S,4S,5R)-2-{4-[(cyclopropanesulfonyl) carbamoyl]phenyl}-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

(1S,4S,5R)-2-[2-fluoro-4-(methanesulfonylcarbamoyl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

(1S,4S,5R)-2-{2-fluoro-4-[(propane-1-sulfonyl) carbamoyl]phenyl}-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

(1S,4S,5R)-2-[4-(2H-1,2,3,4-tetrazol-5-yl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

(1S,4S,5R)-2-[2-fluoro-4-(2H-1,2,3,4-tetrazol-5-yl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate;

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid;

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3,5-difluorobenzoic acid;

4-[(1S,4S,5R)-5-{[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4S,5R)-5-{[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid;

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-methanesulfonylbenzamide;

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(propane-1-sulfonyl) benzamide;

N-(cyclopropanesulfonyl)-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzamide;

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluoro-N-(propane-1-sulfonyl) benzamide;

N-(cyclopropanesulfonyl)-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzamide; and

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3,5-difluorobenzonitrile.

18. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

19. A compound selected from the group consisting of:

4-[(1S,4R,5R)-5-{[4-cyclopropyl-1-(2,6-dichlorophenyl)-1H-pyrazol-5-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-(oxane-4-sulfonyl) benzamide;

3-{4-[(1S,4R,5R)-5-{[4-cyclopropyl-1-(2,6-dichlorophenyl)-1H-pyrazol-5-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}propanoic acid;

4-[(1S,4R,5R)-5-{[4-cyclopropyl-1-(2,6-dichlorophenyl)-1H-pyrazol-5-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4R,5R)-5-{[4-cyclopropyl-1-(2,6-dichlorophenyl)-1H-pyrazol-5-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-{[(1R,2R)-2-hydroxycyclopentyl]sulfonyl}benzamide;

(1R,2R)-2-sulfamoylcyclopentyl 4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoate;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-{[(1R,2R)-2-hydroxycyclopentyl]sulfonyl}benzamide;

(1R,2R)-2-sulfamoylcyclopentyl 4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoate;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-[2-(oxolan-3-yl) ethanesulfonyl]benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[2-(oxolan-3-yl) ethanesulfonyl]benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[(oxan-4-yl) methanesulfonyl]benzamide;

4-cyclopropyl-2-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

2-cyclopropyl-4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-[(oxan-4-yl) methanesulfonyl]benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-methylbenzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[(2,2-dimethyloxan-4-yl) sulfonyl]-2-fluorobenzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[(2,2-dimethyloxan-4-yl) sulfonyl]benzamide;

2-({4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) ethane-1-sulfonic acid;

2-({4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) acetic acid;

5-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2,3-dihydro-1H-indene-2-carboxylic acid;

4-[(1S,4R,5R)-5-({5-cyclopropyl-3-[2-fluoro-6-(propan-2-yl) phenyl]-1,2-oxazol-4-yl}methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-ethylbenzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-methylbenzoic acid;

5-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2,3-dihydro-1H-indene-1-carboxylic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2-cyclopropyl-6-fluorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

N-(cyclopropanesulfonyl)-4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzamide;

4-[(1S,4R,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dimethylphenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2-fluoro-6-methylphenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

N-(cyclopropanesulfonyl)-4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzamide;

4-[(1S,4R,5R)-5-{[3-(2-chloro-6-fluorophenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

N-(cyclopentanesulfonyl)-4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-[(oxolan-3-yl) methanesulfonyl]benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-(oxolane-3-sulfonyl) benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[(oxolan-3-yl) methanesulfonyl]benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-(oxolane-3-sulfonyl) benzamide;

3-{4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorophenyl}propanoic acid;

3-{4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}propanoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-(oxane-4-sulfonyl) benzamide;

3-{4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}propanoic acid;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-(oxane-4-sulfonyl) benzamide;

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid;

4-[(1S,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid; and

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid;

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

20. A compound selected from the group consisting of:

4-[(1S,4S,5R)-5-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyloxy]-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-42);

4-[(1S,4S,5R)-5-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyloxy]-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-43);

4-[(1S,4S,5R)-5-[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazole-4-carbonyloxy]-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-44);

(1S,4S,5R)-2-[4-(methanesulfonylcarbamoyl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-45);

(1S,4S,5R)-2-{4-[(propane-1-sulfonyl) carbamoyl]phenyl}-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-46);

(1S,4S,5R)-2-{4-[(cyclopropanesulfonyl) carbamoyl]phenyl}-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-47);

(1S,4S,5R)-2-[2-fluoro-4-(methanesulfonylcarbamoyl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-48);

(1S,4S,5R)-2-{2-fluoro-4-[(propane-1-sulfonyl) carbamoyl]phenyl}-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-49);

(1S,4S,5R)-2-[4-(2H-1,2,3,4-tetrazol-5-yl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-50);

(1S,4S,5R)-2-[2-fluoro-4-(2H-1,2,3,4-tetrazol-5-yl) phenyl]-2-azabicyclo [2.2.1]heptan-5-yl 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylate (I-51);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-52);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-53);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3,5-difluorobenzoic acid (I-54);

4-[(1S,4S,5R)-5-{[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-56);

4-[(1S,4S,5R)-5-{[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-57);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-methanesulfonylbenzamide (I-58);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(propane-1-sulfonyl) benzamide (I-59);

N-(cyclopropanesulfonyl)-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzamide (I-60);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluoro-N-(propane-1-sulfonyl) benzamide (I-61);

N-(cyclopropanesulfonyl)-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzamide (I-62);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3,5-difluorobenzonitrile (I-54a) 2-Cyano-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-101);

3-cyano-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-102);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid (I-103);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2,6-difluorobenzoic acid (I-104);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2,5-difluorobenzoic acid (I-105);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-(trifluoromethyl) benzoic acid (I-106);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-methylbenzoic acid (I-107);

3-cyclopropyl-4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl) benzoic acid (I-108);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-ethylbenzoic acid (I-109);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-2,3-difluorobenzoic acid (I-110);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-2-methylbenzoic acid (I-111);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-2-methoxybenzoic acid (I-112);

4-[(1S,4S,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-113);

4-[(1S,4S,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-benzoic acid (I-114);

4-[(1S,4S,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid (I-115);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dimethylphenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-116);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dimethylphenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-117);

4-[(1S,4S,5R)-5-{[3-(2-chloro-6-fluorophenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-118);

4-[(1S,4S,5R)-5-{[3-(2-chloro-6-fluorophenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-119);

4-[(1S,4S,5R)-5-({5-cyclopropyl-3-[2-(trifluoromethyl) phenyl]-1,2-oxazol-4-yl}methoxy)-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-120);

4-[(1S,4S,5R)-5-({5-cyclopropyl-3-[2-(trifluoromethyl) phenyl]-1,2-oxazol-4-yl}methoxy)-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-121);

4-[(1S,4S,5R)-5-{[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid (I-122);

2-cyano-4-[(1S,4S,5R)-5-{[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-123);

4-[(1S,4S,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-(1-fluorocyclopropyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid (I-124);

4-[(1S,4S,5R)-5-[(5-cyclopropyl-3-{spiro [2.5]octan-6-yl}-1,2-oxazol-4-yl) methoxy]-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-125);

4-[(1S,4S,5R)-5-[(5-cyclopropyl-3-{spiro [2.5]octan-6-yl}-1,2-oxazol-4-yl) methoxy]-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-126);

(1S,4S,5R)-2-(4-carboxyphenyl)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-ium-2-olate (I-127);

4-[(1R,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-131);

4-[(1R,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-132);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2,6-difluorobenzonitrile (I-133) (1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-[2-fluoro-4-(2H-1,2,3,4-tetrazol-5-yl) phenyl]-2-azabicyclo [2.2.1]heptane (I-134);

(2R)-6-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (I-137)

(2S)-6-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (I-138);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-hydroxy-3-methylbenzamide (I-139);

1-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}-2,2,2-trifluoroethan-1-one (I-142);

2-{N-methyl4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzenesulfonamido}acetic acid (I-143);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzene-1-sulfonic acid (I-144);

2-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}acetic acid (I-146);

3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}propanoic acid (I-147);

4-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}butanoic acid (I-148);

1-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}cyclopropane-1-carboxylic acid (I-149);

1-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}cyclobutane-1-carboxylic acid (I-150);

3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}cyclobutane-1-carboxylic acid (I-151);

3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}butanoic acid (I-152);

2-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}acetic acid (I-153);

3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}propanoic acid (I-154);

3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorophenyl}propanoic acid (I-155);

3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorophenyl}-2,2-dimethylpropanoic acid (I-156);

4-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}butanoic acid (I-157);

3-{3-cyano-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}propanoic acid (I-158);

3-{4-[(1S,4S,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}propanoic acid (I-159);

1-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}methyl) azetidine-3-carboxylic acid (I-160);

N-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}methyl)-N-hydroxyformamide (I-161);

(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-{2-fluoro-4-[2-(2H-1,2,3,4-tetrazol-5-yl) ethyl]phenyl}-2-azabicyclo [2.2.1]heptane (I-162);

2-[bis (2-hydroxyethyl) amino]ethyl 3-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}propanoate (I-163);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(2H-1,2,3,4-tetrazol-5-ylmethyl) benzamide (I-164);

2-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) acetic acid (I-165);

2-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) ethane-1-sulfonic acid (I-166);

2-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorophenyl}formamido) acetic acid (I-167);

2-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorophenyl}formamido) ethane-1-sulfonic acid (I-168);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(2-methanesulfonylethyl) benzamide (I-169);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-(2-methanesulfonylethyl) benzamide (I-170);

N-[2-(cyclopropanesulfonyl) ethyl]-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzamide (I-171);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-[2-(oxane-4-sulfonyl) ethyl]benzamide (I-172);

[2-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-methylphenyl}formamido) ethyl]phosphonic acid (I-173);

({[2-({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-methylphenyl}formamido) ethyl]({[(2,2-dimethylpropanoyl) oxy]methoxy}) phosphoryl}oxy) methyl 2,2-dimethylpropanoate (I-174);

(2-{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}ethyl) phosphonic acid (I-175);

({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}methyl) phosphonic acid (I-176);

methyl 4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoate (I-177);

N-(cyclohexanesulfonyl)-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]benzamide (I-181);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(oxane-4-sulfonyl) benzamide (I-182);

N-(cyclobutylsulfonyl)-4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl) benzamide (I-183);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(oxetan-3-ylsulfonyl) benzamide (I-184);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-((tetrahydrofuran-3-yl) sulfonyl) benzamide (I-185);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(((tetrahydrofuran-3-yl) methyl) sulfonyl) benzamide (I-186);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-((1-methylpiperidin-4-yl) sulfonyl) benzamide (I-187);

N-((1H-pyrazol-4-yl) sulfonyl)-4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl) benzamide (I-188);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(phenylsulfonyl) benzamide (I-189);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluoro-N-(isopentylsulfonyl) benzamide (I-190);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluoro-N-(pentylsulfonyl) benzamide (I-191);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluoro-N-(octylsulfonyl) benzamide (I-192);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-((2-(2-ethoxyethoxy) ethyl) sulfonyl)-3-fluorobenzamide (I-193);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-2-fluoro-N-(propylsulfonyl) benzamide (I-194);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl)-2-fluorobenzamide (I-195);

N-(cyclopropylsulfonyl)-4-((1S,4S,5R)-5-((3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl) benzamide (I-196);

N-(cyclopropylsulfonyl)-4-((1S,4S,5R)-5-((3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorobenzamide (I-197);

4-((1S,4S,5R)-5-((3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluoro-N-(propylsulfonyl) benzamide (I-198);

(1S,4S,5R)-2-(4-((cyclopropylsulfonyl) carbamoyl)-2-fluorophenyl)-2-azabicyclo [2.2.1]heptan-5-yl 3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl) isoxazole-4-carboxylate (I-199);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2-(trifluoromethyl) phenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluoro-N-(propylsulfonyl) benzamide (I-200);

N-(butylsulfonyl)-4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2-(trifluoromethyl) phenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorobenzamide (I-201);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2-(trifluoromethyl) phenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl)-3-fluorobenzamide (I-202);

4-((1S,4S,5R)-5-((3-(2-chloro-6-methylphenyl)-5-cyclopropylisoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-((tetrahydro-2H-pyran-4-yl) sulfonyl) benzamide (I-203);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(2-hydroxyethanesulfonyl) benzamide (I-210);

2-[({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) sulfonyl]ethyl acetate (I-211);

2-[({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) sulfonyl]ethyl cyclopropanecarboxylate (I-212);

2-[({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) sulfonyl]ethyl 2-methylpropanoate (I-213);

3-[({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) sulfonyl]propyl acetate (I-214);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(3-hydroxypropanesulfonyl) benzamide (I-215);

4-[({4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) sulfonyl]butan-2-yl acetate (I-216);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(3-hydroxybutanesulfonyl) benzamide (I-217);

4-({4-[{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido)sulfonyl]butan-2-yl}oxy)-4-oxobutanoic acid (I-218);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(3,4-dihydroxybutanesulfonyl) benzamide (I-219);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-{[(1s,4s)-4-hydroxycyclohexyl]sulfonyl}benzamide (I-220) and 4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-{[(1r,4r)-4-hydroxycyclohexyl]sulfonyl}benzamide (I-221);

4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-N-(dodecane-1-sulfonyl)-3-fluorobenzamide (I-222);

(2R,3S,4R,5R)—N-{10-[{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}formamido) sulfonyl]decyl}-2,3,4,5,6-pentahydroxyhexanamide (I-223);

N-{10-[{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}formamido) sulfonyl]decyl}acetamide (I-224);

N-{10-[{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}formamido) sulfonyl]decyl}-2-methoxyacetamide (I-225);

{10-[{4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}formamido) sulfonyl]decyl}diethylmethylazanium (I-226);

N-[10-(azetidin-1-yl) decanesulfonyl]-4-[(1S,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzamide (I-227);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(spiro [2.5]octan-6-yl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl) benzamide (I-228);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(spiro [2.5]octan-6-yl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl)-3-fluorobenzamide (I-229);

4-((1S,4S,5R)-5-((5-cyclopropyl-3-(spiro [2.5]octan-6-yl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluoro-N-((tetrahydro-2H-pyran-4-yl) sulfonyl) benzamide (I-230);

4-((1R,4R,5S)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl)-3-fluorobenzamide (I-231);

4-((1R,4R,5S)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl) benzamide (I-232);

(1S,4S,5R)-2-{4-[(cyclopropanesulfonyl) carbamoyl]phenyl}-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-ium-2-olate (I-234);

3-{4-[(1S,4S,5R)-5-{[3-(2-chloro-6-fluorophenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}-N-(oxane-4-sulfonyl) propanamide (I-235);

3-(4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-(methylsulfonyl) propanamide (I-236);

3-(4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-(cyclopropylsulfonyl) propanamide (I-237);

3-(4-((1S,4S,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-((tetrahydro-2H-pyran-4-yl) sulfonyl) propanamide (I-238);

3-(4-((1S,4S,5R)-5-((3-(2-chloro-6-fluorophenyl)-5-cyclopropylisoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-(methylsulfonyl) propanamide (I-239);

3-(4-((1S,4S,5R)-5-((3-(2-chloro-6-fluorophenyl)-5-cyclopropylisoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-(cyclopropylsulfonyl) propanamide (I-240);

3-(4-((1S,4S,5R)-5-((3-(2-chloro-6-methylphenyl)-5-cyclopropylisoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-(methylsulfonyl) propanamide (I-241);

3-(4-((1S,4S,5R)-5-((3-(2-chloro-6-methylphenyl)-5-cyclopropylisoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-(cyclopropylsulfonyl) propanamide (I-242);

3-(4-((1S,4S,5R)-5-((3-(2-chloro-6-methylphenyl)-5-cyclopropylisoxazol-4-yl) methoxy)-2-azabicyclo [2.2.1]heptan-2-yl)-3-fluorophenyl)-N-((tetrahydro-2H-pyran-4-yl) sulfonyl) propanamide (I-243);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-244);

4-[(1S,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-245);

3-{4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}propanoic acid (I-303);

3-{4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorophenyl}propanoic acid (I-304);

3-{4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorophenyl}propanoic acid (I-305);

4-[(1S,4R,5R)-5-{[3-(2-chloro-6-fluorophenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-306);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2-fluoro-6-methylphenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-307);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dimethylphenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-308);

4-[(1S,4R,5R)-5-{[3-(2-chloro-6-methylphenyl)-5-cyclopropyl-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-309);

4-[(1S,4R,5R)-5-({5-cyclopropyl-3-[2-fluoro-6-(propan-2-yl) phenyl]-1,2-oxazol-4-yl}methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-310);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2-cyclopropyl-6-fluorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-311);

5-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2,3-dihydro-1H-indene-1-carboxylic acid (I-312) 5-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2,3-dihydro-1H-indene-2-carboxylic acid (I-313);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid (I-314);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-315);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-methylbenzoic acid (I-316);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-3-methylbenzoic acid (I-317);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-ethylbenzoic acid (I-318);

2-cyclopropyl-4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-319);

4-cyclopropyl-2-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-320);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[(2,2-dimethyloxan-4-yl) sulfonyl]benzamide (I-329);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-[(2,2-dimethyloxan-4-yl) sulfonyl]-2-fluorobenzamide (I-330);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl)-2-fluorobenzamide (I-331);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-2-fluoro-N-((tetrahydro-2H-pyran-4-yl) sulfonyl) benzamide (I-332);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-2-fluoro-N-(((tetrahydro-2H-pyran-4-yl) methyl) sulfonyl) benzamide (I-333);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-2-fluoro-N-((tetrahydrofuran-3-yl) sulfonyl) benzamide (I-334);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-2-fluoro-N-(((tetrahydrofuran-3-yl) methyl) sulfonyl) benzamide (I-335);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-2-fluoro-N-((2-(tetrahydrofuran-3-yl) ethyl) sulfonyl) benzamide (I-336);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-(cyclopropylsulfonyl) benzamide (I-337);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-((tetrahydro-2H-pyran-4-yl) sulfonyl) benzamide (I-338);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-(((tetrahydro-2H-pyran-4-yl) methyl) sulfonyl) benzamide (I-339);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-((tetrahydrofuran-3-yl) sulfonyl) benzamide (I-340);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-(((tetrahydrofuran-3-yl) methyl) sulfonyl) benzamide (I-341);

4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl)-N-((2-(tetrahydrofuran-3-yl) ethyl) sulfonyl) benzamide (I-342);

N-(cyclopentylsulfonyl)-4-((1S,4R,5R)-5-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy)-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl) benzamide (I-343);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-N-{[(1R,2R)-2-hydroxycyclopentyl]sulfonyl}benzamide (I-344) (1R,2R)-2-sulfamoylcyclopentyl 4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]benzoate (I-345);

4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluoro-N-{[(1R,2R)-2-hydroxycyclopentyl]sulfonyl}benzamide (I-346);

(1R,2R)-2-sulfamoylcyclopentyl 4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoate (I-347)

2-({4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) acetic acid (I-358);

2-({4-[(1S,4R,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-oxo-2-azabicyclo [2.2.1]heptan-2-yl]phenyl}formamido) ethane-1-sulfonic acid (I-359);

4-[(1S,3R,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-methyl-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-360);

4-[(1R,3S,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-methyl-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-361);

4-[(1S,3R,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-methyl-2-azabicyclo [2.2.1]heptan-2-yl]-2-fluorobenzoic acid (I-362);

4-[(1S,3R,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-methyl-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-363);

4-[(1R,3S,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-methyl-2-azabicyclo [2.2.1]heptan-2-yl]-3-fluorobenzoic acid (I-364);

4-[(1S,3R,4S,5R)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-ethyl-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-365); and

4-[(1R,3S,4R,5S)-5-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-3-ethyl-2-azabicyclo [2.2.1]heptan-2-yl]benzoic acid (I-366);

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2022

From: CHAO, JIANHUA; JAIN, RAKESH; HU, LILY; LEWIS, JASON G; BARIBAULT, HELENE; CALDWELL, JEREMY

To: ARDELYX, INC.

Reel/Frame 061314/0868 →

Continuity (5)

Continuation 16990827 · Aug 11, 2020

Continuation 16327791

Provisional Application 62532983 · Jul 14, 2017

Provisional Application 62378625 · Aug 23, 2016

Related Publication 20230139597A1 · May 4, 2023

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