US2019315687A1PendingUtilityA1
Substituted Pyrrolidines and Methods of Use

Assignee: ABBVIE SARLPriority: Oct 7, 2016Filed: Jun 14, 2019Published: Oct 17, 2019
Est. expiryOct 7, 2036(~10.2 yrs left)· nominal 20-yr term from priority
Inventors:Robert J. Altenbach Andrew Bogdan Nicolas Desroy Gregory A. Gfesser Stephen N. Greszler John R. Koenig Philip R. Kym Bo Liu Marc J. Scanio Xenia B. Searle Xueqing Wang Ming C. Yeung Gang Zhao
A61P 11/00C07D 405/14A61K 45/06A61K 31/4709A61K 31/4439C07D 403/12C07D 401/14C07D 207/16C07D 401/12A61K 31/506A61K 31/40
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Claims
Abstract

wherein R1, R2, R2A, R3, R3A, R4, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.
Claims

exact text as granted — not AI-modified
What is claimed: 
     
         1 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein
 R 1  is selected from the group consisting of SO 2 R 6 , C(O)R 6 , C(O)OR 6 , and C(O)NR 7 R 8 ; 
 R 2  is C(O)OH or a bioisostere thereof, 
 R 2A  is selected from the group consisting of hydrogen, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, and C 3 -C 6  cycloalkyl; 
 R 3  is selected from the group consisting of C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein the R 3  C 1 -C 6  alkyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkoxy, OH, oxo, CN, NO 2 , F, Cl, Br and I; wherein the R 3  C 3 -C 6  cycloalkyl, phenyl, and 5-6 membered heteroaryl are optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, OH, oxo, CN, NO 2 , F, Cl, Br and I; and 
 R 3A  is selected from the group consisting of hydrogen, C 1 -C 6  alkyl, and C 1 -C 6  haloalkyl; or 
 R 3  and R 3A , together with the carbon to which they are attached, form a C 3 -C 6  cycloalkyl; wherein the C 3 -C 6  cycloalkyl formed from R 3  and R 3A  and the carbon to which they are attached is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 4  is selected from the group consisting of L 1 -C 6 -C 10  aryl, L 1 -5-11 membered heteroaryl, L 1 -4-12 membered heterocyclyl, L 1 -C 3 -C 11  cycloalkyl, and L 1 -C 4 -C 11  cycloalkenyl; wherein the R 4  C 6 -C 10  aryl, 5-11 membered heteroaryl, 4-12 membered heterocyclyl, C 3 -C 11  cycloalkyl, and C 4 -C 11  cycloalkenyl are optionally substituted with one or more substituents independently selected from the group consisting of R 9 , OR 9 , C(O)OR 9 , C(O)NR 10 R 11 , SR 9 , NR 10 R 11 , Si(R 9 ) 3 , SF 5 , SO 2 R 9 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 L 1  is absent, or is selected from the group consisting of C 1 -C 6  alkylene, C 2 -C 6  alkenylene, C 2 -C 6  alkynylene, and C 1 -C 6  alkylene-O—; wherein the L 1  C 1 -C 6  alkylene, C 2 -C 6  alkenylene, and C 2 -C 6  alkynylene, alone or as part of a group, are optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkoxy, OH, and oxo; 
 R 5  is selected from the group consisting of C 6 -C 10  membered aryl, 5-11 membered heteroaryl, 4-6 membered monocyclic heterocycle fused to a phenyl group, C 3 -C 11  cycloalkyl, and C 4 -C 11  cycloalkenyl; wherein the R 5  C 6 -C 10  membered aryl, 5-11 membered heteroaryl, 4-6 membered monocyclic heterocycle fused to a phenyl group, C 3 -C 11  cycloalkyl, and C 4 -C 11  cycloalkenyl are optionally substituted with one or more substituents independently selected from the group consisting of R 12 , OR 12 , NR 13 R 14 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 6  is selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein the R 6  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are optionally substituted with one or more substituents independently selected from the group consisting of R 15 , OR 15 , SR 15 , NR 16 R 17 , OH, CN, NO 2 , F, Cl, Br and I; wherein the R 6  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl are optionally substituted with one or more substituents independently selected from the group consisting of R 18 , OR 18 , C(O)R 18 , OC(O)R 18 , C(O)OR 18 , SO 2 R 18 , NR 19 R 20 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 7  and R 8  are each independently hydrogen or C 1 -C 6  alkyl; 
 R 9 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11 cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 9  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 21 , OR 21 , C(O)R 21 , OC(O)R 21 , C(O)OR 21 , C(O)NR 22 R 23 , SO 2 R 21 , NR 22 R 23 , OH, oxo, CN, NO 2 , F, Cl, Br and I; wherein each R 9  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R 24 , OR 24 , C(O)R 24 , OC(O)R 24 , C(O)OR 24 , SO 2 R 24 , NR 25 R 26 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 10  and R 11 , at each occurrence, are each independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, phenyl, and 5-6 membered heteroaryl; wherein each R 10  and R 11  phenyl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 12 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 12  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, N(C 1 -C 6  alkyl) 2 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 13  and R 14 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 15 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 5  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of OH, oxo, CN, NO 2 , F, Cl, Br and I; wherein each R 15  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, oxo, OH, CN, NO 2 , F, Cl, Br and I; 
 R 16  and R 17 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 18 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 6 -C 10  membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 18  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 6 -C 10  membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, 5-6 membered heteroaryl, OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 19  and R 20 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 21 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 21  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 22  and R 23 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 24 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  alkoxy- C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; and 
 R 25  and R 26 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl, 
 in combination with a pharmaceutically acceptable carrier. 
 
       
     
     
         2 . The composition of  claim 1 , wherein the composition comprises one potentiator, and one or more additional correctors. 
     
     
         3 . The composition of  claim 1 , wherein the composition comprises one or more additional therapeutic agents. 
     
     
         4 . The composition of  claim 3 , wherein the additional therapeutic agents are selected from the group consisting of CFTR modulators and CFTR amplifiers. 
     
     
         5 . The composition of  claim 3 , wherein the additional therapeutic agents are CFTR modulators. 
     
     
         6 . The composition of  claim 1 , wherein the compound is selected from the group consisting of:
 rac-(2R,3S,5R)-3-tert-butyl-1-(cyclopentylacetyl)-4-[(2,5-dichlorophenyl)methoxy]-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-4-[(5-chloro-2-methoxyphenyl)methoxy]-1-(cyclohexanecarbonyl)-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(2,5-dichlorophenyl)methoxy]-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[6-methyl-4-(trifluoromethyl)pyridin-2-yl]oxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-4-[(4,6-dimethoxypyrimidin-2-yl)oxy]-1-[di(propan-2-yl)carbamoyl]-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-[di(propan-2-yl)carbamoyl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2R*,3S*,4R*,5R*)-3-tert-butyl-1-[di(propan-2-yl)carbamoyl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S*,3R*,4S*,5S*)-3-tert-butyl-1-[di(propan-2-yl)carbamoyl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(4,6-dimethoxypyrimidin-5-yl)methoxy]-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(4,6-dimethoxypyrimidin-2-yl)methoxy]-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-(dimethylamino)-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-methoxyphenyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}pyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-4-[(4-chloro-2-methoxyphenyl)methoxy]-1-(cyclohexanecarbonyl)-5-(2-methoxyphenyl)pyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-[2-(dimethylamino)pyridin-3-yl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}pyrrolidine-2-carboxylic acid;   rac-(2R,3S,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-N-(methanesulfonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxamide;   rac-(2R,3S,5R)-3-tert-butyl-4-[(5-chloro-2-methoxyphenyl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2R,3S,4R,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-N-(2-methoxyethanesulfonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxamide;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-N-(1-methylcyclopropane-1-sulfonyl)-5-phenylpyrrolidine-2-carboxamide;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-N-(cyclopropanesulfonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxamide;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-N-(ethanesulfonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxamide;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-N-(dimethylsulfamoyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxamide;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-N-(methanesulfonyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxamide;   (2R,3S,4R,5R)-3-tert-butyl-1-[(1S,3S)-3-methoxycyclohexane-1-carbonyl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2R,3S,4R,5R)-3-tert-butyl-1-[(1S,3S)-3-methoxycyclohexane-1-carbonyl]-4-{[6-methyl-4-(trifluoromethyl)pyridin-2-yl]oxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-(tert-butyl)-4-((2-methoxy-5-(trifluoromethyl)benzyl)oxy)-1-((1R,3R)-3-methoxycyclohexanecarbonyl)-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-[(1S,3S)-3-methoxycyclohexane-1-carbonyl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-[(1R,3R)-3-methoxycyclohexane-1-carbonyl]-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-[(1S,3S)-3-methoxycyclohexane-1-carbonyl]-4-{[2-methoxy-4-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-[(1R,3R)-3-methoxycyclohexane-1-carbonyl]-4-{[2-methoxy-4-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-tert-butyl-1-[(cyclobutyloxy)carbonyl]-4-{[2-methoxy-4-(trifluoromethyl)phenyl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   rac-(2R,3S,4R,5R)-3-tert-butyl-4-[(5-chloro-2-methoxyphenyl)methoxy]-1-[(cyclobutyloxy)carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxyphenyl)methoxy]-3-tert-butyl-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxyphenyl)methoxy]-3-tert-butyl-1-[(1R,3R)-3-methoxycyclohexane-1-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(4-methoxy[1,1′-biphenyl]-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(4-methoxy[1,1′-biphenyl]-3-yl)methoxy]-1-[(1R,3R)-3-methoxycyclohexane-1-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxypyridin-3-yl)methoxy]-3-tert-butyl-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-5-phenylpyridin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclohexyl-2-methoxypyridin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclopentyl-2-methoxypyridin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-1-[(1R,3R)-3-methoxycyclohexane-1-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxypyridin-3-yl)methoxy]-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)-4-[(2-methoxy-5-phenylpyridin-3-yl)methoxy]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(5-cyclopentyl-2-methoxypyridin-3-yl)methoxy]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-{[5-(bicyclo[2.2.1]heptan-2-yl)-2-methoxypyridin-3-yl]methoxy}-3-tert-butyl-1-(cyclohexanecarbonyl)-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(5-cyclopentyl-2-methoxypyridin-3-yl)methoxy]-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-{[5-(bicyclo[2.2.1]heptan-2-yl)-2-methoxypyridin-3-yl]methoxy}-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)-4-{[2-methoxy-5-(pyrrolidin-1-yl)pyridin-3-yl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-1-[(1R,3R)-3-methoxycyclohexane-1-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(2-fluoro-4-methylphenyl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(2-fluorophenyl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(4-fluoro-2-methylphenyl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(2,4-difluorophenyl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(3,6-dihydro-2H-pyran-4-yl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(3-methoxyphenyl)pyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(4-methylphenyl)pyridin-3-yl]methoxy}-5-phenyl-1-{[propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(6-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-fluorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-(2-fluorophenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-(2-fluorophenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxypyridin-3-yl)methoxy]-3-tert-butyl-5-(2-fluorophenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-fluorophenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-(3-chiorophenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(piperidin-1-yl)pyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(pyrrolidin-1-yl)pyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(3,3-difluoroazetidin-1-yl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(3,3-difluoropyrrolidin-1-yl)-2-methoxypyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-phenyl-1-{[(prop-2-en-1-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxane-2-carbonyl]-5-phenylpyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-cyclopropylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-cyclobutyl-5-methoxypyridin-4-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-cyclobutylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]phenyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-[2-(3,6-dihydro-2H-pyran-4-yl)phenyl]-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3S)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-(oxane-4-carbonyl)-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3R)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-cyclopropylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[2-(trifluoromethyl)pyridin-3-yl]pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[2-(trifluoromethyl)pyridin-3-yl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[3-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(3-bromophenyl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-cyclopropylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(3-bromophenyl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chlorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-5-(2-bromophenyl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-cyclopropylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2R)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(oxane-4-carbonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2R)-oxane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-cyclopropylphenyl)-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-cyclobutylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chlorophenyl)-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-cyclopropylphenyl)-4-[(2-methoxyquinolin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}-5-[2-(trifluoromethyl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]-5-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-cyclopropylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-cyclopropylphenyl)-1-(oxane-4-carbonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-1-(ethoxycarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(1R,2S,4S)-7-oxabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxolane-2-carbonyl]-5-[2-(trifluoromethyl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[2-(trifluoromethyl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-tert-butylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclobutanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclobutanecarbonyl)-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-3-tert-butyl-1-(cyclopentanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-[2-(difluoromethyl)phenyl]-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4R,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2,6-difluorophenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-cyclopropylphenyl)-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-cyclopropylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-5-(2-cyclopropylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxypyridin-3-yl)methoxy]-3-tert-butyl-5-(2-cyclopropylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)phenyl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-4-(trifluoromethyl)phenyl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-ethylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-([1,1′-biphenyl]-2-yl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-(2-cyclopropylphenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(2-bromophenyl)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-ethylphenyl)-4-{[2-methoxy-4-(trifluoromethyl)phenyl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-ethylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-2-methoxypyridin-3-yl)methoxy]-3-tert-butyl-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[5-(2-cyanopropan-2-yl)-2-methoxyphenyl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxyquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(4′-fluoro[1,1′-biphenyl]-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3′-chloro[1,1′-biphenyl]-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-(1-methyl-1H-pyrazol-4-yl)phenyl]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-[3′-(dimethylamino)[1,1′-biphenyl]-2-yl]-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2′-methyl[1,1′-biphenyl]-2-yl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-[2-(pyridin-4-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-[2-(pyrimidin-5-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-[2-(furan-3-yl)phenyl]-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-(1-methyl-1H-pyrrol-3-yl)phenyl]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2′-chloro[1,1′-biphenyl]-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-[3′-(trifluoromethoxy)[1,1′-biphenyl]-2-yl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(4′-chloro[1,1′-biphenyl]-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-[2-(2H-1,3-benzodioxol-5-yl)phenyl]-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2′-fluoro[1,1′-biphenyl]-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-[2-(6-methoxypyridin-3-yl)phenyl]-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-[4′-(trifluoromethoxy)[1,1′-biphenyl]-2-yl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(4′-cyano[1,1′-biphenyl]-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-{2-[6-(trifluoromethyl)pyridin-3-yl]phenyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-[2-(5-ethoxypyridin-3-yl)phenyl]-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(naphthalen-1-yl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-5-(naphthalen-1-yl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-5-(1-benzofuran-7-yl)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-(2-methylpropyl)phenyl]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-cyclopropylphenyl)-1-(6-methoxypyridine-2-sulfonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(1-methylcyclobutyl)phenyl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2,3-dihydro-1-benzofuran-7-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclopropyl-2-methoxypyridin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-(5,6,7,8-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-(5,6,7,8-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-7-methylquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(6-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(3,4-dihydro-2H-pyran-6-carbonyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-chloro-2-methoxypyridin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethoxy)phenyl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)—N-(6-aminopyridine-2-sulfonyl)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-cyclopropylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxamide;   (2S,3R,4S,5S)-3-tert-butyl-4-[(6-tert-butyl-3-methoxypyridin-2-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-({[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]( 2 H 2 )methyl}oxy)-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[{2-[( 2 H 3 )methyloxy]-5-(trifluoromethyl)pyridin-3-yl}( 2 H 2 )methyl]oxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(5-chloro-2-methylphenyl)-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(5-chloro-2-methylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chloro-2-methylphenyl)-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(3-chloro-2-methylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[{2-[( 2 H 3 )methyloxy]-5-(trifluoromethyl)phenyl}( 2 H 2 )methyl]oxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[(5-tert-butyl-2-methoxyphenyl)( 2 H 2 )methyl]oxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-chloro-5,7-dimethylquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-5,8-dimethylquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-5,7-dimethylquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-(2-methoxyphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-methoxyphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-5-(2-methoxyphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-6,8-dimethylquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(1-methylcyclopropyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-8-methylquinolin-3-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(1-methylcyclobutyl)phenyl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(2-methoxy-5,8-dimethylquinolin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-({2-[2-methoxy-5-(trifluoromethyl)phenyl]prop-2-en-1-yl}oxy)-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-1-(cyclohexanecarbonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-[(2-methoxy-5,7-dimethylquinolin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(2-methoxy-5,7-dimethylquinolin-3-yl)methoxy]-1-{[(propan-2-yl)oxy]carbonyl}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-ethylphenyl)-4-[(2-methoxyquinolin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(1-methyl-1H-benzimidazol-2-yl)methoxy]-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-1-(cyclohexanecarbonyl)-3-(2-methoxypropan-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-(2-methoxypropan-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-{[(propan-2-yl)oxy]carbonyl}-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-(2-methoxypropan-2-yl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{2-[2-methoxy-5-(trifluoromethyl)phenyl]propoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{(2S)-2,3-dihydroxy-2-[2-methoxy-5-(trifluoromethyl)phenyl]propoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{(2R)-2,3-dihydroxy-2-[2-methoxy-5-(trifluoromethyl)phenyl]propoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{2-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxoethoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-{[(1,1,1-trifluoropropan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-({[(2R)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{2-hydroxy-2-[2-methoxy-5-(trifluoromethyl)phenyl]ethoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{2-methoxy-2-[2-methoxy-5-(trifluoromethyl)phenyl]ethoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-3-(2-methoxypropan-2-yl)-1-[(2S)-oxane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{(2R)-2-[2-methoxy-5-(trifluoromethyl)phenyl]propoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{(2S)-2-[2-methoxy-5-(trifluoromethyl)phenyl]propoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-({[(2S)-1,1,1-trifluoropropan-2-yl]oxy}carbonyl)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-[1-(trifluoromethyl)cyclopropane-1-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-[1-(trifluoromethyl)cyclopentane-1-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-({3-[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]prop-2-yn-1-yl}oxy)-5-phenyl-1-{[(propan-2-yl)oxy]carbonyl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-ethylphenyl)-4-({3-[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]prop-2-yn-1-yl}oxy)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-4-{[5-(trifluoromethyl)-1-benzofuran-3-yl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-ethylphenyl)-4-{3-[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]propoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(5-iodo-2-methylphenyl)-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-[(1R,2R)-2-(trifluoromethyl)cyclohexane-1-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}-1-[(1S,2S)-2-(trifluoromethyl)cyclohexane-1-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{2-[(5-chloro-2-methoxypyridin-3-yl)oxy]ethoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-tert-butyl-2-methoxyphenyl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-[2-( 2 H 3 )methylphenyl]-1-[(2S,3S)-(2,3- 2 H 2 )oxane-2-carbonyl](2- 2 H)pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-1-(cyclohexanecarbonyl)-4-{[2-methoxy-5-(1-methylcyclopropyl)pyridin-3-yl]methoxy}-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{2-[2-methoxy-5-(trifluoromethyl)phenoxy]ethoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-4-[(5-bromo-1-benzofuran-2-yl)methoxy]-3-tert-butyl-1-[(2S)-oxane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(6-tert-butyl-2-methoxypyridin-3-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(6-tert-butyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-5-(2-ethylphenyl)-1-[(2S)-oxane-2-carbonyl]-4-{[7-(trifluoromethyl)-1-benzofuran-2-yl]methoxy}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-chloro-1-benzofuran-2-yl)methoxy]-5-(2-ethylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(naphthalene-1-sulfonyl)-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-2-methoxypyridin-3-yl)methoxy]-1-(cyclohexanecarbonyl)-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; and   (2S,3R,4S,5S)-3-tert-butyl-4-[(5-cyclobutyl-1-benzofuran-2-yl)methoxy]-1-[(2S)-oxane-2-carbonyl]-5-{2-[(propan-2-yl)oxy]pyridin-3-yl}pyrrolidine-2-carboxylic acid.   
     
     
         7 . The composition of  claim 1 , wherein the compound is selected from the group consisting of:
 (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3 S)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3R)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[3-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid; and   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid.   
     
     
         8 . The composition of  claim 1 , wherein the compound is either
 (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3S)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; or   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3R)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof.   
     
     
         9 . The composition of  claim 1 , wherein the compound is (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[3-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The composition of  claim 1 , wherein the compound is (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The composition of  claim 1 , wherein the compound is (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. 
     
     
         12 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (III), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein
 R 1  is selected from the group consisting of SO 2 R 6 , C(O)R 6 , C(O)OR 6 , and C(O)NR 7 R 8 ; 
 R 4  is selected from the group consisting of L 1 -C 6 -C 10  aryl, L 1 -5-11 membered heteroaryl, L 1 -4-12 membered heterocyclyl, L 1 -C 3 -C 11  cycloalkyl, and L 1 -C 4 -C 11  cycloalkenyl; wherein the R 4  C 6 -C 10  aryl, 5-11 membered heteroaryl, 4-12 membered heterocyclyl, C 3 -C 11  cycloalkyl, and C 4 -C 11  cycloalkenyl are optionally substituted with one or more substituents independently selected from the group consisting of R 9 , OR 9 , C(O)OR 9 , C(O)NR 10 R 11 , SR 9 , NR 10 R 11 , Si(R 9 ) 3 , SF 5 , SO 2 R 9 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 L 1  is absent, or is selected from the group consisting of C 1 -C 6  alkylene, C 2 -C 6  alkenylene, C 2 -C 6  alkynylene, and C 1 -C 6  alkylene-O—; wherein the L 1  C 1 -C 6  alkylene, C 2 -C 6  alkenylene, and C 2 -C 6  alkynylene, alone or as part of a group, are optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkoxy, OH, and oxo; 
 R 5  is selected from the group consisting of C 6 -C 10  membered aryl, 5-11 membered heteroaryl, 4-6 membered monocyclic heterocycle fused to a phenyl group, C 3 -C 11  cycloalkyl, and C 4 -C 11  cycloalkenyl; wherein the R 5  C 6 -C 10  membered aryl, 5-11 membered heteroaryl, 4-6 membered monocyclic heterocycle fused to a phenyl group, C 3 -C 11  cycloalkyl, and C 4 -C 11  cycloalkenyl are optionally substituted with one or more substituents independently selected from the group consisting of R 12 , OR 12 , NR 13 R 14 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 6  is selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein the R 6  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl are optionally substituted with one or more substituents independently selected from the group consisting of R 15 , OR 15 , SR 15 , NR 16 R 17 , OH, CN, NO 2 , F, Cl, Br and I; wherein the R 6  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl are optionally substituted with one or more substituents independently selected from the group consisting of R 18 , OR 18 , C(O)R 18 , OC(O)R 18 , C(O)OR 18 , SO 2 R 18 , NR 19 R 20 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 7  and R 8  are each independently hydrogen or C 1 -C 6  alkyl; 
 R 9 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 9  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R 21 , OR 21 , C(O)R 21 , OC(O)R 21 , C(O)OR 21 , C(O)NR 22 R 23 , SO 2 R 21 , NR 22 R 23 , OH, oxo, CN, NO 2 , F, Cl, Br and I; wherein each R 9  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R 24 , OR 24 , C(O)R 24 , OC(O)R 24 , C(O)OR 24 , SO 2 R 24 , NR 25 R 26 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 10  and R 11 , at each occurrence, are each independently selected from the group consisting of hydrogen, C 1 -C 6  alkyl, phenyl, and 5-6 membered heteroaryl; wherein each R 10  and R 11  phenyl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 12 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 12  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, N(C 1 -C 6  alkyl) 2 , OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 13  and R 14 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 15 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 15 C 1 -C 6  alkyl, C 2 -C 6  alkenyl, and C 2 -C 6  alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of OH, oxo, CN, NO 2 , F, Cl, Br and I; wherein each R 15  6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, oxo, OH, CN, NO 2 , F, Cl, Br and I; 
 R 16  and R 17 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 18 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 6 -C 10  membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 18  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 6 -C 10  membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  alkoxy, 5-6 membered heteroaryl, OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 19  and R 20 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 21 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; wherein each R 21  C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of OH, oxo, CN, NO 2 , F, Cl, Br and I; 
 R 22  and R 23 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl; 
 R 24 , at each occurrence, is independently selected from the group consisting of C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, C 1 -C 6  alkoxy- C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, 6-10 membered aryl, 5-11 membered heteroaryl, C 3 -C 11  cycloalkyl, C 4 -C 11  cycloalkenyl, and 4-12 membered heterocyclyl; and 
 R 25  and R 26 , at each occurrence, are each independently hydrogen or C 1 -C 6  alkyl. 
 
       
     
     
         13 . The composition of  claim 12 , wherein the composition comprises one potentiator, and one or more additional correctors. 
     
     
         14 . The composition of  claim 12 , wherein the composition comprises one or more additional therapeutic agents. 
     
     
         15 . The composition of  claim 14 , wherein the additional therapeutic agents are selected from the group consisting of CFTR modulators and CFTR amplifiers. 
     
     
         16 . The composition of  claim 14 , wherein the additional therapeutic agents are CFTR modulators. 
     
     
         17 . The composition of  claim 12 , wherein the compound is selected from the group consisting of:
 (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2R)-oxolane-2-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3 S)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3R)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[3-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid;   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid; and   (2S,3R,4S,5 S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid.   
     
     
         18 . The composition of  claim 12 , wherein the compound is either
 (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3S)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; or   (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(3R)-oxolane-3-carbonyl]-5-[2-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof.   
     
     
         19 . The composition of  claim 12 , wherein the compound is (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-1-[(2S)-oxolane-2-carbonyl]-5-[3-(propan-2-yl)phenyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The composition of  claim 12 , wherein the compound is (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxolane-2-carbonyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. 
     
     
         21 . The composition of  claim 12 , wherein the compound is (2S,3R,4S,5S)-3-tert-butyl-4-{[2-methoxy-5-(trifluoromethyl)pyridin-3-yl]methoxy}-5-(2-methylphenyl)-1-[(2S)-oxane-2-carbonyl]pyrrolidine-2-carboxylic acid; or a pharmaceutically acceptable salt thereof.
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