TRPV4 antagonists

1. A compound according to Formula I:

wherein:

R 1 is selected from:

aryl,

aryl substituted from 1 to 4 times by R a ,

heteroaryl,

heteroaryl substituted from 1 to 4 times by R a ,

bicycloheteroaryl, and

bicycloheteroaryl substituted from 1 to 4 times by R a ;

R 2 is selected from:

aryl,

aryl substituted from 1 to 4 times by R b ,

heteroaryl,

heteroaryl substituted from 1 to 4 times by R b ,

bicycloheteroaryl, and

bicycloheteroaryl substituted from 1 to 4 times by R b , and

Y 1 is selected from:

C 1-6 alkyl, and

C 1-6 alkyl substituted with from: 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OC 1-6 alkyl,

—OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and CN,

mercapto,

—S(O)H,

—S(O) 2 H,

oxo,

hydroxy,

amino,

NHR x11 ,

where R x11 is selected from C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , CN, —OC 1-5 alkyl, —OC 1-5 alkyl substituted from 1 to 6 times by fluoro and —NH 2 ,

NR x12 R x13 ,

where R x12 and R x13 are each independently selected from C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and —CN,

—C(O)NH 2 ,

aryl,

—Oaryl,

heteroaryl,

—Oheteroaryl,

—S(O) 2 NH 2 ,

—NHS(O) 2 H,

nitro, and

cyano, or

Y 1 is taken together with the adjacent —OH to form a heterocyclic ring selected from:

morpholinyl,

morpholinyl substituted by —CH 3 , and

oxazolidin-2-one;

each R a is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

cyano,

—OC 1-6 alkyl,

—OC 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

—Ophenyl,

—C(O)OC 1-6 alkyl,

—C(O)OC 1-6 alkyl substituted 1 to 5 times by fluoro, and

—Ocycloalkyl; and

each R b is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

cyano,

—OC 1-6 alkyl,

—OC 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

phenyl,

C 1-4 alkylphenyl,

—C≡C—Si(CH 3 ) 3 , and

—C≡C-cycloalkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound according to Formula (I) of claim 1 , wherein the compound is represented by the following Formula (II):

wherein:

R 21 is selected from:

aryl,

aryl substituted from 1 to 3 times by R a2 ,

heteroaryl,

heteroaryl substituted from 1 to 3 times by R a2 ,

bicycloheteroaryl, and

bicycloheteroaryl substituted from 1 to 3 times by R a2 ;

R 22 is selected from:

aryl,

aryl substituted from 1 to 3 times by R b2 ,

bicycloheteroaryl,

bicycloheteroaryl substituted from 1 to 3 times by R b2 ;

heteroaryl, and

heteroaryl substituted from 1 to 3 times by R b2 , and

Y 21 is selected from:

C 1-6 alkyl, and

C 1-6 alkyl substituted with from: 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OC 1-6 alkyl,

—OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and —CN,

mercapto,

—S(O)H,

—S(O) 2 H,

oxo,

hydroxy,

amino,

—NHR x21 ,

where R x21 is selected from C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and —CN,

—NR x22 R x23 ,

where R x22 and R x23 are each independently selected from C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and —CN,

—C(O)NH 2 ,

aryl,

—Oaryl,

heteroaryl,

—Oheteroaryl,

—S(O) 2 NH 2 ,

—NHS(O) 2 H,

nitro, and

cyano, or

Y 21 is taken together with the adjacent —OH to form a heterocyclic ring selected from:

morpholinyl,

morpholinyl substituted by —CH 3 , and

oxazolidin-2-one;

each R a2 is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

cyano,

—OC 1-6 alkyl,

—OC 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

—Ophenyl,

—C(O)OC 1-5 alkyl,

—C(O)OC 1-5 alkyl substituted 1 to 5 times by fluoro, and

—Ocycloalkyl; and

each R b2 is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

cyano,

—OC 1-6 alkyl,

—OC 1-6 alkyl substituted with from 1 to 5 substituents independently selected from: fluoro, chloro, bromo, iodo, C 1-4 alkoxy, —OH, C 1-4 alkyl, phenyl, oxo, —NO 2 , —NH 2 and —CN,

phenyl,

C 1-4 alkylphenyl,

—C≡C—Si(CH 3 ) 3 , and

—C≡C-cycloalkyl;

or a pharmaceutically acceptable salt thereof.

3. A compound according to Formula (I) of claim 1 , wherein the compound is represented by the following Formula (III):

wherein:

R 31 is selected from:

phenyl,

phenyl substituted from 1 to 3 times by R a3 ,

benzo[c][1,2,5]oxadiazolyl,

benzo[c][1,2,5]oxadiazolyl substituted from 1 to 3 times by R a3 ,

pyrimidinyl,

pyrimidinyl substituted from 1 to 3 times by R a3 ,

naphthalenyl,

naphthalenyl substituted from 1 to 3 times by R a3 ,

pyridinyl, and

pyridinyl substituted from 1 to 3 times by R a3 ;

R 32 is selected from:

phenyl,

phenyl substituted from 1 to 3 times by R b3 ,

pyridinyl,

pyridinyl substituted from 1 to 3 times by R b3 ,

benzo[c][1,2,5]oxadiazolyl,

benzo[c][1,2,5]oxadiazolyl substituted from 1 to 3 times by R b3 ,

thiophenyl,

thiophenyl substituted from 1 to 3 times by R b3 ,

thiazolyl,

thiazolyl substituted from 1 to 3 times by R b3 ,

pyrazolyl,

pyrazolyl substituted from 1 to 3 times by R b3 ,

imidazo[2,1-b]thiazolyl,

imidazo[2,1-b]thiazolyl substituted from 1 to 3 times by R b3 ,

pyrimidinyl,

pyrimidinyl substituted from 1 to 3 times by R b3 ,

pyridazinyl, and

pyridazinyl substituted from 1 to 3 times by R b3 ; and

Y 31 is selected from:

—CH 2 OH,

—CH(OH)CH 3 ,

—CH(OH)CH 2 CH 3 ,

—CH(OH)CH 2 CH 2 CH 3 ,

—CH(OH)CH 2 CH(CH 3 ) 2 ,

—C(OH)(CH 3 ) 2 ,

—CH 2 NH 2 ,

—CH 2 NHR x30 ,

—CH 2 NR x30 R x30 ,

—CH(NH 2 )CH 3 , or

Y 31 is taken together with the adjacent —OH to form a heterocyclic ring selected from:

morpholinyl,

morpholinyl substituted by —CH 3 , and

oxazolidin-2-one,

where each R x30 is independently selected from: C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and —CN;

each R a3 is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

cyano,

—CF 3 ,

—C 1-5 alkylCF 3 ,

—CHF 2 ,

—CH 2 F,

—OC 1-5 alkyl,

—OCF 3 ,

—OC 1-5 alkylCF 3 ,

—Ophenyl,

—Obenzyl,

—C 1-5 alkylCN,

—C(O)OC 1-5 alkyl,

—C(O)OH, and

—Ocycloalkyl; and

each R b3 is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

cyano,

—CF 3 ,

—C 1-5 alkylCF 3 ,

—CHF 2 ,

—CH 2 F,

—OC 1-5 alkyl,

—OCF 3 ,

—OC 1-5 alkylCF 3 ,

—C(O)CH 3 ,

—OCHF 2 ,

phenyl,

—C≡C—Si(CH 3 ) 3 ,

—C≡C-cycloalkyl, and

—C≡C-phenyl;

or a pharmaceutically acceptable salt thereof.

4. A compound according to Formula (I) of claim 1 , wherein the compound is represented by the following Formula (IV):

wherein:

R 41 is selected from:

phenyl, and

phenyl substituted from 1 to 3 times by R a4 ;

R 42 is selected from:

phenyl,

phenyl substituted from 1 to 3 times by R b4 ,

pyridinyl, and

pyridinyl substituted from 1 to 3 times by R b4 ; and

Y 41 is selected from:

—CH 2 OH,

—CH 2 NH 2 ,

—CH 2 NHR x40 ,

—CH 2 NR x40 R x40 , and

—CH(NH 2 )CH 3 , or

Y 41 is taken together with the adjacent —OH to form a heterocyclic ring selected from:

morpholinyl,

morpholinyl substituted by —CH 3 , and

oxazolidin-2-one,

where each R x40 is independently selected from: C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, —OH, —NH 2 , and —CN;

each R a4 is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

cyano,

—CF 3 ,

—C 1-5 alkylCF 3 ,

—CHF 2 ,

—CH 2 F,

—OC 1-5 alkyl,

—OCF 3 ,

—OC 1-5 alkylCF 3 ,

—Ophenyl,

—Obenzyl,

—C 1-5 alkylCN,

—C(O)OC 1-5 alkyl,

—C(O)OH, and

—Ocycloalkyl; and

each R b4 is independently selected from:

fluoro,

chloro,

bromo,

iodo,

—OH,

C 1-6 alkyl,

cyano,

—CF 3 ,

—C 1-5 alkylCF 3 ,

—CHF 2 ,

—CH 2 F,

—OC 1-5 alkyl,

—OCF 3 ,

—OC 1-5 alkylCF 3 ,

—C(O)CH 3 ,

—OCHF 2 ,

phenyl,

—C≡C—Si(CH 3 ) 3 ,

—C≡C-cycloalkyl, and

—C≡C-phenyl;

or a pharmaceutically acceptable salt thereof.

5. A compound according to Formula (I) of claim 1 selected from:

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2,4-dichlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

(3R,4S)-1-((2,4-dichlorophenyl)sulfonyl)-4-(3,4-difluorophenoxy)-3-(hydroxymethyl)pyrrolidin-3-01;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-(trifluoromethyl)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(benzo[c][1,2,5]oxadiazol-5-yloxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

5-chloro-2-(((3R,4S)-4-(3,4-difluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-methoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-ethoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

5-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)pyrimidine-2-carbonitrile;

2-(((3R,4S)-4-(2-chloro-4-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2,3-difluorobenzonitrile;

2-(((3R,4S)-4-(4-cyano-2-methylphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-(trifluoromethyl)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

6-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-naphthonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2,5-difluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2,6-difluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-(trifluoromethoxy)benzonitrile;

5-chloro-2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(3,4,5-trifluorophenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-chloro-2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,3,4-trifluorophenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-chloro-2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,4,5-trifluorophenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

2-(((3R,4S)-4-(3,4-difluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(3,4,5-trifluorophenoxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,4,5-trifluorophenoxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(2,3,4-trifluorophenoxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-chloro-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3-fluoro-4-(trifluoromethyl)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-(cyanomethyl)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3-(cyanomethyl)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

methyl 5-cyano-2-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)benzoate;

(3R,4S)-1-((2,4-dichlorophenyl)sulfonyl)-3-(hydroxymethyl)-4-((6-(trifluoromethyl)pyridin-3-yl)oxy)pyrrolidin-3-ol;

5-(((3S,4R)-1-((2,4-dichlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-3-fluoropicolinonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-fluoro-3-(trifluoromethyl)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3,4-dichlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3-fluoro-4-(trifluoromethoxy)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3-chloro-4-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-((6-(trifluoromethyl)pyridin-3-yl)oxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3-fluoro-4-methoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-isopropoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-cyclopropoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-phenoxypyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-chloro-2-methoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

4-(((3S,4R)-1-((2-chloro-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethoxy) phenoxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(p-tolyloxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-methoxyphenoxy) pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(3-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(5-cyano-2-methoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-((2-(trifluoromethyl)pyrimidin-5-yl)oxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl) pyrrolidin-3-yl)oxy)-1-naphthonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((7-chlorobenzo[c][1,2,5]oxadiazol-4-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-(benzo[c][1,2,5]oxadiazol-5-ylsulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

3-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

4-(((3S,4R)-1-((2-chloro-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-bromo-4-methoxyphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-bromo-4-(trifluoromethoxy)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-chloro-4-(trifluoromethoxy)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-bromo-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-cyano-2-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

5-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)picolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((4-(trifluoromethyl)phenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((4-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-acetyl-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

5-(((3S,4R)-1-((2,4-dichlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)picolinonitrile;

5-(((3S,4R)-1-((2-chloro-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)picolinonitrile;

5-(((3S,4R)-1-((2-chloro-4-methylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)picolinonitrile;

5-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2,4,6-trichlorophenyl)sulfonyl)pyrrolidin-3-yl)oxy)picolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2,4,6-trichlorophenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((2-chloro-4-methylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

5-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

4-(((3S,4R)-1-((4-cyano-2-methylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2-methyl-4-(trifluoromethyl)phenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

5-(((3R,4S)-4-(4-cyano-2,5-difluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((5-(trifluoromethyl)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((2-chlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chlorothiophen-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2-methyl-4-(trifluoromethyl)thiazol-5-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((2,4-dichlorothiazol-5-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-chloro-1-methyl-1H-pyrazol-5-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((6-chloroimidazo[2,1-b]thiazol-5-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((6-chloropyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2,6-dichloropyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-ethynylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2,3-dichlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((3-chloro-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2,6-dichloro-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-chloro-4-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-(difluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((6-bromopyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-chloro phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-bromo phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((4-iodophenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((4-cyano-2-methoxyphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-bromopyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

3-chloro-4-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)benzonitrile;

2-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)benzonitrile;

3-bromo-4-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

3-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((4-(2,2,2-trifluoroethyl)phenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((5-(trifluoromethyl)thiophen-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((4-cyano-2-fluorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-iodophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-chloro-4-iodophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-1-((3-fluoro-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((2-bromophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-1-((3-fluoro-4-methylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2-iodophenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((2-bromo-4-chlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-bromo-2-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-(difluoromethoxy)pyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-bromo-1-methyl-1H-pyrazol-5-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-chloro-1,3-d methyl-1H-pyrazol-5-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

(3R,4S)-4-(benzo[c][1,2,5]oxadiazol-5-yloxy)-1-((2-fluoro-4-(trifluoromethyl)phenyl)sulfonyl)-3-(hydroxymethyl)pyrrolidin-3-ol;

4-(((3S,4R)-1-((6-(difluoromethoxy)pyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((5-(trifluoromethoxy)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((2-(trifluoromethyl)pyrimidin-5-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((4-chloro-3-(trifluoromethoxy)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((5-iodopyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

5-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-6-methylpicolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-(trifluoromethoxy)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-(2,2,2-trifluoroethoxy)pyridazin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((6-(difluoromethoxy)pyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-fluorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

3-(((3S,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

4-(((3S,4S)-1-((2-chloro-4-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2,4-dichlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((4-bromo-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-bromo-4-fluorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-methoxyphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-(((3S,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3S,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-fluorobenzonitrile;

2-(((3S,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

5-fluoro-2-(((3S,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

3-chloro-4-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-chloro-2-(((3S,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-chloro-2-(((3S,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-fluoro-2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

5-chloro-2-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)benzonitrile;

2-(((3R,4S)-4-(4-chlorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-fluorobenzonitrile;

5-chloro-2-(((3R,4S)-3-hydroxy-3-(hydroxymethyl)-4-(4-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)sulfonyl)benzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-methoxybenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-5-ethoxy-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-propoxybenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-isopropoxybenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-hydroxybenzonitrile;

5-(benzyloxy)-4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

5-butoxy-4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-isobutoxybenzonitrile;

2-(((3R,4S)-4-(4-cyano-2-propoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-(2,2,2-trifluoroethoxy)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-hydroxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(2-butoxy-4-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(4-cyano-2-isobutoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

2-(((3R,4S)-4-(2-(benzyloxy)-4-cyanophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-5-(trifluoromethyl)benzonitrile;

4-(((3S,4R)-1-((4-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-3-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile;

5-(((3R,4S)-4-(4-cyano-5-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-(trifluoromethyl)pyridin-3-yl)sulfonyl) pyrrolidin-3-yl)oxy)-5-(2,2,2-trifluoroethoxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-(phenylsulfonyl) pyrrolidin-3-yl)oxy)-5-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((2,4-dichlorophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((4-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-isobutoxybenzonitrile;

4-(((3S,4R)-1-((4-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-isobutoxybenzonitrile;

5-(((3R,4S)-4-(4-cyano-5-fluoro-2-isobutoxyphenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((4-(trifluoromethyl)phenyl)sulfonyl) pyrrolidin-3-yl)oxy)-5-isobutoxybenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-(trifluoromethyl)pyridin-3-yl)sulfonyl) pyrrolidin-3-yl)oxy)-5-isobutoxybenzonitrile;

5-(((3R,4S)-4-(4-cyano-2-(2,2,2-trifluoroethoxy)phenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

4-(((3S,4R)-1-((2-cyanophenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-3-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-3-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-methylpyridazin-3-yl)sulfonyl) pyrrolidin-3-yl)oxy)-5-isobutoxybenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxybutyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxyethyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxy-3-methylbutyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(1-hydroxyethyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-((R)-1-methoxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxypropyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxy-3-methylbutyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxybutyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-methoxyphenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyanophenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-fluorophenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

3-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-((S)-1-hydroxyethyl)pyrrolidin-1-yl)sulfonyl)picolinonitrile;

4-(((3S,4R)-1-((2,4-dichlorophenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-chloro-4-cyanophenyl)sulfonyl)-4-hydroxy-4-((S)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-((R)-1-hydroxyethyl)-1-((6-(trifluoromethyl)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-1-((5-fluoropyridin-2-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-((R)-1-hydroxyethyl)-1-((6-(trifluoromethoxy)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-((R)-1-hydroxyethyl)-1-((4-iodophenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-((R)-1-hydroxyethyl)-1-((5-(trifluoromethoxy)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((5-(difluoromethyl)pyridin-2-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((6-(difluoromethyl)pyridin-3-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((6-(difluoromethoxy)pyridin-3-yl)sulfonyl)-4-hydroxy-4-((R)-1-hydroxyethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluoro-5-(2,2,2-trifluoroethoxy)benzonitrile;

4-(((3S,4R)-1-((2-cyano-4-methylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-ethylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)-[1,1′-biphenyl]-3-carbonitrile;

4-(((3S,4R)-1-((2-cyano-4-(prop-1-yn-1-yl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-ethynylphenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-cyano-4-((trimethylsilyl)ethynyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((4-(prop-1-yn-1-yl)phenyl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((6-(prop-1-yn-1-yl)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((4-cyano-2-(prop-1-yn-1-yl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((2-ethynyl-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((6-(cyclopropylethynyl)pyridin-3-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((5-(prop-1-yn-1-yl)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4R)-1-((5-ethynylpyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((5-(3,3-dimethylbut-1-yn-1-yl)pyridin-2-yl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

2-fluoro-4-(((3S,4R)-4-hydroxy-4-(hydroxymethyl)-1-((5-(phenylethynyl)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)benzonitrile;

6-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)nicotinonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethoxy)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-4-(aminomethyl)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxy-4-(((2-hydroxyethyl)amino)methyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-((methylamino)methyl) pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-((ethylamino)methyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-1-((2-cyano-4-(trifluoromethyl)phenyl)sulfonyl)-4-hydroxy-4-((isopropylamino)methyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((4-chloro-1-methyl-1H-pyrazol-5-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-fluoropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

5-(((3S,4S)-3-(aminomethyl)-4-(4-cyano-3-fluorophenoxy)-3-hydroxpyrrolidin-1-yl)sulfonyl)picolinonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-(difluoromethyl)pyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-4-hydroxy-1-((6-(trifluoromethyl)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)benzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-(difluoromethoxy)pyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-4-hydroxy-1-((5-(trifluoromethoxy)pyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-4-hydroxy-1-((6-(trifluoromethoxy)pyridin-3-yl)sulfonyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-4-hydroxy-1-((5-iodopyridin-2-yl)sulfonyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-bromopyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((4S,5R)-2-((4-chloro-2-cyanophenyl)sulfonyl)-9-methyl-6-oxa-2,9-diazaspiro[4.5]decan-4-yl)oxy)-2-fluorobenzonitrile;

4-(((4S,5S)-2-((4-chloro-2-cyanophenyl)sulfonyl)-6-oxa-2,9-diazaspiro[4.5]decan-4-yl)oxy)-2-fluorobenzonitrile;

4-(((5S,9S)-7-((4-chloro-2-cyanophenyl)sulfonyl)-2-oxo-1-oxa-3,7-diazaspiro[4.4]nonan-9-yl)oxy)-2-fluorobenzonitrile;

4-(((5R,9S)-7-((4-chloro-2-cyanophenyl)sulfonyl)-2-oxo-1-oxa-3,7-diazaspiro[4.4]nonan-9-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-4-((R)-1-aminoethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-4-((S)-1-aminoethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile; and

((3R,4S)-1-((5-chloropyridin-2-yl)sulfonyl)-4-(4-cyano-3-fluorophenoxy)-3-hydroxpyrrolidin-3-yl)methyl 2-aminoacetate;

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a compound of Formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

7. A method of treating a disease state selected from: atherosclerosis, acute respiratory distress syndrome, acute lung injury, asthma, cough, acute cough, sub-acute cough, chronic cough, pain, in a human in need thereof, which comprises administering to such human a safe and effective amount of a compound according to Formula (I) of claim 1 , or a pharmaceutically acceptable salt thereof.

8. A method according to claim 7 wherein the compound or pharmaceutically acceptable salt thereof is administered orally.

9. A method according to claim 7 wherein the compound or pharmaceutically acceptable salt thereof is administered intravenously.

10. A method according to claim 7 wherein the compound or pharmaceutically acceptable salt thereof is administered by inhalation.

11. A method according to claim 7 wherein the disease state is acute lung injury.

12. A method according to claim 7 wherein the disease state is acute respiratory distress syndrome.

13. A method of inhibiting TRPV4 activity in a human in need thereof, which comprises administering to such human a safe and effective amount of a compound according to Formula (I) claim 1 , or a pharmaceutically acceptable salt thereof.

14. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable excipient and a safe and effective amount of a compound according to Formula (I) of claim 1 or a pharmaceutically acceptable salt thereof, which process comprises bringing the compound of Formula (I) or the pharmaceutically acceptable salt thereof into association with the pharmaceutically acceptable excipient.

15. A compound according to Formula (I) of claim 1 selected from:

6-(((3R,4S)-4-(4-cyano-3-fluorophenoxy)-3-hydroxy-3-(hydroxymethyl)pyrrolidin-1-yl)sulfonyl)nicotinonitrile;

4-(((3S,4R)-1-((2-cyano-4-(trifluoromethoxy)phenyl)sulfonyl)-4-hydroxy-4-(hydroxymethyl)pyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

4-(((3S,4R)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile; and

4-(((3S,4R)-4-(aminomethyl)-1-((4-chloro-2-cyanophenyl)sulfonyl)-4-hydroxpyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

or a pharmaceutically acceptable salt thereof.

16. A compound which is:

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile;

or a pharmaceutically acceptable salt thereof.

17. The compound:

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile, according to claim 16 .

18. A pharmaceutically acceptable salt of:

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile, according to claim 16 .

19. A pharmaceutically acceptable salt according to claim 18 which is:

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile, esylate anhydrate.

20. A pharmaceutically acceptable salt according to claim 18 which is:

4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile, esylate monohydrate.

21. A method of treating a disease state selected from: atherosclerosis, acute respiratory distress syndrome, acute lung injury, asthma, cough, acute cough, sub-acute cough, chronic cough, and pain, in a human in need thereof, which comprises administering to such human a safe and effective amount of 4-(((3S,4S)-4-(aminomethyl)-1-((5-chloropyridin-2-yl)sulfonyl)-4-hydroxypyrrolidin-3-yl)oxy)-2-fluorobenzonitrile, or a pharmaceutically acceptable salt thereof.