Compounds, pharmaceutical composition and methods for use in treating inflammatory diseases
Compounds of formula I are useful in treating and/or preventing inflammatory diseases.
1. A method for treating in a patient the development of an inflammatory disease, comprising the administration, to a patient in need thereof, of a pharmaceutically effective amount of a compound of formula Ia-1b′:
or a pharmaceutically acceptable salt thereof, wherein
R 1 and R 2 are H,
D is C═O;
L 2 is single bond;
R is H or linear or branched alkyl, aryl, acyloxyalkyl or dioxolene;
Ar 1 is a 5- to 6-membered aryl or heteroaryl group, 3- to 6-membered cycloalkyl group, or a linear or branched C 3 -C 6 alkyl group, each of which being optionally substituted by one or more group(s) selected from halo, cyano, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, hydroxyl, alkoxy, haloalkoxy, amino, alkylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, haloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino, or two substituents form an alkylenedioxy group or a haloalkylenedioxy group, each of said aryl or heteroaryl substituents being optionally substituted by one or more further substituents selected from halo, cyano, alkyl, haloalkyl, hydroxyl, alkoxy, and haloalkoxy;
Ar 2 is an aryl or heteroaryl, cycloalkyl, monocyclic heterocyclyl or C 2 -C 6 alkyl group, each of which being optionally substituted by one or more group(s) selected from halo, cyano, nitro, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, benzoxazol-2-yl, heteroarylalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, cycloalkylalkyloxy, heterocyclyloxy, aryloxy, heteroaryloxy, alkoxyalkyl, haloalkoxyalkyl, arylalkyloxy, heteroarylalkyloxy, aryloxyalkyl, heteroaryloxyalkyl, amino, alkylamino, arylcarbonyl, carboxy, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, alkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, arylcarbamoyl, heteroarylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, sulfamoyl, alkylsulfamoyl, arylsulfamoyl, heteroarylsulfamoyl, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, oxo, or two substituents form an alkylenedioxy group or a haloalkylenedioxy group, or fused to the aryl, heteroaryl or cycloalkyl group may be one or more aryl or heteroaryl moiety, each of said substituents being optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aryloxy, aralkyloxy optionally substituted by a fluoro group, carboxy, alkoxycarbonyl, alkylcarbonyloxy, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, carbamoylamino, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, heterocyclylsulfonyl, arylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino, oxo, and haloalkoxyalkyl;
R 3 is H, cyano, alkyl, hydroxyalkyl, aralkyl, alkoxyalkyl, acetyl or arylsulfonyl;
R 3′ is H or C 1 -C 4 alkyl; and
R 4 is H, cyano, C 1 -C 4 alkyl;
under the condition that the compound of formula (Ia-1b′) is not
(2S)-methyl 1-benzoyl-5-mesitylpyrrolidine-2-carboxylate,
(2S)-methyl 1-benzoyl-5-(2,4,6-triethylphenyl)pyrrolidine-2-carboxylate,
(2S,5S)-1-benzoyl-5-mesitylpyrrolidine-2-carboxylic acid,
(2S)-methyl 1-benzoyl-5-propylpyrrolidine-2-carboxylate,
(2S,5S)-methyl 1-benzoyl-5-propylpyrrolidine-2-carboxylate,
(2S,5R)-methyl 1-benzoyl-5-propylpyrrolidine-2-carboxylate,
(2S,5R)-5-(tert-butyl)-1-(4-phenylbutanoyl)pyrrolidine-2-carboxylic acid,
(2S,5R)-methyl 5-(tert-butyl)-1-(4-phenylbutanoyl)pyrrolidine-2-carboxylate,
(2R,5R)-1-(4-bromothiophene-2-carbonyl)-5-phenylpyrrolidine-2-carboxylic acid,
(2R,5S)-1-(3-bromo-2,6-dimethoxybenzoyl)-5-phenylpyrrolidine-2-carboxylic acid, or
1-[7-(4-tert-butyl-phenoxy)-1-cyclopentylmethyl-isoquinoline-3-carbonyl]-(5R)-phenyl-pyrrolidine-(2S)-carboxylic acid,
and under the condition that:
Ar 2 is not phthalazin-6-yl, pyrido[2,3-d]pyridazin-2-yl, pyrido[2,3-d]pyridazin-3-yl, or pyrazino[2,3-d]pyridazin-2-yl; and/or
R 3 is not a mono substituted hydroxymethyl.
2. The method according to claim 1 , wherein the compound has the formula Ib-1b′:
or a pharmaceutically acceptable salt thereof, wherein
D, L 2 , Ar 1 , Ar 2 , R, R 1 , R 2 , R 3 , R 3′ and R 4 are as previously defined.
3. The method according to claim 2 , wherein the compound has the formula Ib-1d:
or a pharmaceutically acceptable salt thereof, wherein
Ar 1 , Ar 2 , R 1 , R 2 and R are as previously defined.
4. The method according to claim 3 , wherein the compound has the formula Ib-1e:
or a pharmaceutically acceptable salt thereof, wherein
Ar 2 , R 1 , R 2 and R are as previously defined; and
R 8 , R 8′ , R 9 , R 9′ and R 10 are independently selected from H, halo, cyano, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, hydroxyl, haloalkoxy, alkylamino, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, haloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, or one or more of R 8 and R 9 , or R 9 and R 10 , or R 10 and R 9′ , or R 9′ and R 8′ form an alkylenedioxy group or a haloalkylenedioxy group together with the phenyl group they are attached to, each of said substituents being optionally substituted by one or more further substituents selected from halo, cyano, alkyl, haloalkyl, hydroxyl, alkoxy and haloalkoxy.
5. The method according to claim 4 , wherein the compound has the formula Ib-1g:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are independently selected from H, halo, cyano, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, hydroxyl, haloalkoxy, alkylamino, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, haloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, or one or more of R 8 and R 9 , or R 9 and R 10 , or R 10 and R 9′ , or R 9′ and R 8′ form an alkylenedioxy group or a haloalkylenedioxy group together with the phenyl group they are attached to, each of said substituents being optionally substituted by one or more further substituents selected from halo, cyano, alkyl, haloalkyl, hydroxyl, alkoxy and haloalkoxy; and
R 11 , R 11′ , R 12 , R 12′ and R 16 are independently selected from H, halo, cyano, nitro, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, heterocyclyloxy, aryloxy, heteroaryloxy, alkoxyalkyl, haloalkoxyalkyl, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, aryloxyalkyl, heteroaryloxyalkyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, alkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, arylcarbamoyl, heteroarylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, sulfamoyl, alkylsulfamoyl, arylsulfamoyl, heteroarylsulfamoyl, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, or one or more of R 11 and R 12 , or R 12 and R 16 , or R 16 and R 12 ′, or R 12 ′ and R 11′ form an alkylenedioxy group or a haloalkylenedioxy group together with the phenyl group they are attached to, or one or more of R 11 and R 12 , or R 12 and R 16 , or R 16 and R 12 ′, or R 12 ′ and R 11′ form together an aryl or heteroaryl moiety fused to the phenyl group they are attached to, each of said substituents being optionally substituted by one or more further substituents selected from halo, cyano, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, aryl optionally substituted by one a chloro or methyl group, heteroaryl, heteroalkyl, hydroxyl, alkoxy, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aryloxy, aralkyloxy optionally substituted by one fluoro, amino, alkylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, carbamoylamino, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino and oxo.
6. The method according to claim 5 , wherein the compound has the formula Ib-1g1:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined; and
R 16 is as previously defined.
7. The method according to claim 6 , wherein the compound has the formula Ib-1g1a:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined; and
R 17 , R 17′ , R 18′ and R 19 are independently selected from H, halo, cyano, alkyl, haloalkyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, hydroxyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, alkoxyalkyl, cycloalkylalkyloxy, aryloxy, aralkyloxy, alkylamino, alkylsulfonyl, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino.
8. The method according to claim 5 , wherein the compound has the formula Ib-1g2:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined; and
R 12 and R 12′ are as previously defined.
9. The method according to claim 5 , wherein the compound has the formula Ib-1h:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined;
L 4 is a single bond, —C(O)—, —O—, —O—C 1 -C 3 -alkylene or —C 1 -C 3 -alkylene-O— optionally substituted by one or more group selected from fluoro or methyl;
R 11 , R 11′ , R 12 and R 12′ are as previously defined; and
R 13 , R 13′ , R 14 , R 14′ and R 15 are independently selected from H, halo cyano, alkyl, haloalkyl, cyanomethyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, alkoxyalkyl, cycloalkylalkyloxy, aralkyloxy optionally substituted by one fluoro, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino.
10. The method according to claim 9 , wherein the compound has the formula Ib-1h1:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined; and
R 12 R 13 , R 13′ , R 14 , R 14′ and R 15 are as previously defined.
11. The method according to claim 5 , wherein the compound has the formula Ib-1h′:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined;
R 12 is as previously defined;
R 16 is selected from the group of heteroaryl moieties consisting of:
wherein the arrow marks the attachment point to the phenyl ring; and
R 17 , R 17′ , R 18 , R 18′ and R 19 are independently selected from H, halo, cyano, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, alkoxyalkyl, cycloalkylalkyloxy, aralkyloxy, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino.
12. The method according to claim 5 , wherein the compound has the formula Ib-1h″:
or a pharmaceutically acceptable salt thereof, wherein
R 8 is F or Cl and R 9 is H, or both R 8 and R 9 are F;
R is H, methyl, ethyl or tert-butyl; and
A 0 , A 0′ , A 1 , A 2 , A 3 , A 4 and A 5 are selected from the combinations 1 to 24:
Combination
No.
A 0
A 0′
A 1
A 2
A 3
A 4
A 5
1
CH
CH
C—OCH 3
CH
C—NHSO 2 CH 3
CH
CH
2
CH
CH
C—CH 3
C—NHSO 2 CH 3
CH
CH
CH
3
CH
CH
C—OCH 3
N
CH
CH
CH
4
CH
CH
C—OCH 3
N
C—OCH 3
N
CH
5
C—OCH 3
CH
CH
N
C—OCH 3
N
CH
6
CH
CH
C—OCH 3
N
N
C—OCH 3
CH
7
CH
CH
C—OCH 3
CH
CH
C—CN
CH
8
CH
CH
C—CH 3
CH
CH
C—CN
CH
9
C—F
CH
C—OCH 3
N
N
C—OCH 3
CH
10
CH
CH
CH
N
CH
CH
C—OCH 3
11
CH
CH
CH
CH
C—NHSO 2 CH 3
CH
CH
12
CH
CH
CH
C—NHSO 2 CH 3
CH
CH
CH
13
CH
CH
CH
N
C—OCH 3
N
C—OCH 3
15
CH
CH
C—OCH 3
N
CH
N
CH
16
CH
C—OCH 3
C—OCH 3
CH
CH
CH
CH
17
C—OCH 3
CH
CH
N
CH
CH
C—OCH 3
18
C—OCH 3
CH
C—OCH 3
N
C—OCH 3
N
CH
19
CH
CH
C—OCH 3
CH
C—NHCOCH 3
CH
CH
20
CH
CH
C—CN
CH
C—OCH 3
C—OCH 3
CH
21
CH
CH
C—OCH 3
CH
C—N(CH 3 )SO 2 CH 3
CH
CH
23
CH
CH
C—OCH 3
N
CH
N
C—OCH 3
24
CH
CH
C—OCH3
CH
N
CH
CH.
13. The method according to claim 5 , wherein the compound has the formula Ib-1i:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined;
L 4 is a single bond, —C(O)—, —O—, —O—C 1 -C 3 -alkylene or —C 1 -C 3 -alkylene-O— optionally substituted by one or more group selected from fluoro or methyl;
R 12 and R 12′ are as previously defined;
R 13 , R 13′ , R 14 , R 14′ and R 15 are independently selected from H, halo cyano, alkyl, haloalkyl, cyanomethyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, alkoxyalkyl, cycloalkylalkyloxy, aralkyloxy optionally substituted by one fluoro, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino; and
R 16 is as previously defined.
14. The method according to claim 4 , wherein the compound has the formula Ib-1j:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined; and
L 4 is a single bond, —C(O)—, —O—, —O—C 1 -C 3 -alkylene or —C 1 -C 3 -alkylene-O— optionally substituted by one or more group selected from fluoro or methyl;
R 11 , R 11′ and R 12′ are independently selected from H, halo, cyano, nitro, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, heterocyclyloxy, aryloxy, heteroaryloxy, alkoxyalkyl, haloalkoxyalkyl, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, aryloxyalkyl, heteroaryloxyalkyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, alkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, arylcarbamoyl, heteroarylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, sulfamoyl, alkylsulfamoyl, arylsulfamoyl, heteroarylsulfamoyl, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, or R 12′ and R 11′ form an alkylenedioxy group or a haloalkylenedioxy group together with the phenyl group they are attached to, or R 12′ and R 11′ form together an aryl or heteroaryl moiety fused to the phenyl group they are attached to, each of said substituents being optionally substituted by one or more further substituents selected from halo, cyano, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, aryl optionally substituted by one a chloro or methyl group, heteroaryl, heteroalkyl, hydroxyl, alkoxy, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aryloxy, aralkyloxy optionally substituted by one fluoro, amino, alkylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, carbamoylamino, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino and oxo;
R 13 , R 13′ , R 14 , R 14′ and R 15 are are independently selected from H, halo cyano, alkyl, haloalkyl, cyanomethyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, cycloalkyloxy, alkoxyalkyl, cycloalkylalkyloxy, aralkyloxy optionally substituted by one fluoro, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino.
15. The method according to claim 4 , wherein the compound has the formula Ib-1k:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined;
R 12′ is H, fluoro, chloro, CF 3 , methyl or methoxy; and
R 17 , R 17′ , R 18′ and R 19 are independently selected from H, halo, cyano, nitro, alkyl, haloalkyl, alkoxyalkyl, alkoxy, cycloalkylalkyloxy, haloalkoxy, alkoxyalkoxy, amino, alkylcarbonylamino, alkylsulfonyl or alkylsulfonylamino.
16. The method according to claim 4 , wherein the compound has the formula Ib-1l:
or a pharmaceutically acceptable salt thereof, wherein
R is as previously defined;
R 8 , R 8′ , R 9 , R 9′ and R 10 are as previously defined; and
R 20 is an aryl or heteroaryl, each of said aryl or heteroaryl being optionally substituted by one or more substituent(s) selected from halo, alkyl, haloalkyl, cyano, nitro, phenyl optionally substituted by one chloro, alkoxy, heterocyclylsulfonyl, alkylsulfamoyl or alkylsulfonylamino.
17. The method according to claim 1 , wherein the compound has the formula Ic-1b′:
or a pharmaceutically acceptable salt thereof, wherein
D, L 2 , Ar 1 , R, R 1 , R 2 , R 3 , R 3′ and R 4 are as previously defined.
18. The method according to claim 1 , wherein the compound has the formula Id-1b′:
or a pharmaceutically acceptable salt thereof, wherein
D, L 2 , Ar 1 , R, R 1 , R 2 , R 3 , R 3′ and R 4 are as previously defined.
19. The method according to claim 1 , wherein the compound has the formula Ie-1b′:
or a pharmaceutically acceptable salt thereof, wherein
D, L 2 , Ar 1 , Ar 2 , R, R 1 , R 2 , R 3 , R 3′ and R 4 are as previously defined.
20. The method according to claim 1 , wherein the compound is selected from the group consisting of:
1 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
2 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
3 (2S,5R)-1-(3-((4-chlorobenzyl)oxy)-5-methoxybenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
4 (2S,5R)-5-(2-chlorophenyl)-1-(2′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
5 (2S,5R)-5-(2-chlorophenyl)-1-(4′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
6 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-5-phenethoxybenzoyl)pyrrolidine-2-carboxylic acid
8 (2S,5R)-1-([1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
9 (2S,5R)-5-(2-chlorophenyl)-1-(3-(3,3-diphenylpropoxy)-5-methoxybenzoyl)pyrrolidine-2-carboxylic acid
10 (2S,5R)-5-(2-chlorophenyl)-1-(3′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
11 (2S,5R)-5-(2-chlorophenyl)-1-(3′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
12 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-5-((4-(methylsulfonyl)benzyl)oxy)benzoyl)pyrrolidine-2-carboxylic acid
13 (2S,5R)-5-(2-chlorophenyl)-1-(3′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
14 (2S,5R)-5-(2-chlorophenyl)-1-(3,5-dimethoxybenzoyl)pyrrolidine-2-carboxylic acid
15 (2S,5R)-5-(2-chlorophenyl)-1-(4-(phenoxymethyl)benzoyl)pyrrolidine-2-carboxylic acid
16 (2S,5R)-5-(2-chlorophenyl)-1-(4-((2-fluorobenzyl)oxy)benzoyl)pyrrolidine-2-carboxylic acid
17 (2S,5R)-1-(3-chloro-5-methoxybenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
18 (2S,5R)-5-(2-chlorophenyl)-1-(4′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
19 (2S,5R)-5-(2-chlorophenyl)-1-(4-phenethoxybenzoyl)pyrrolidine-2-carboxylic acid
21 (2S,5R)-5-(2-chlorophenyl)-1-(3,5-diethoxybenzoyl)pyrrolidine-2-carboxylic acid
23 (2S,5R)-5-(2-chlorophenyl)-1-(3-phenethoxybenzoyl)pyrrolidine-2-carboxylic acid
24 (2S)-1-([1,1′-biphenyl]-4-carbonyl)-4-benzyl-5-phenylpyrrolidine-2-carboxylic acid
25 (2S,5R)-5-(2-chlorophenyl)-1-(1,2,3,4-tetrahydronaphthalene-2-carbonyl)pyrrolidine-2-carboxylic acid
26 (2S,5R)-5-(2-chlorophenyl)-1-(4-isobutylbenzoyl)pyrrolidine-2-carboxylic acid
27 (2S,5R)-5-(2-chlorophenyl)-1-(2,2-difluorobenzo[d][1,3]dioxole-6-carbonyl)pyrrolidine-2-carboxylic acid
28 (2S,5R)-1-([1,1′-biphenyl]-4-carbonyl)-5-phenylpyrrolidine-2-carboxylic acid
29 (2S,5R)-5-(2-chlorophenyl)-1-(3-fluoro-5-methoxybenzoyl)pyrrolidine-2-carboxylic acid
30 (2S,5R)-5-(2-chlorophenyl)-1-(6-phenylnicotinoyl)pyrrolidine-2-carboxylic acid
31 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-5-(2-methoxyethoxy)benzoyl)pyrrolidine-2-carboxylic acid
32 (2S,5R)-5-(2-chlorophenyl)-1-(3′-methoxy-[1,1′-biphenyl]-3-carbonyl)pyrrolidine-2-carboxylic acid
33 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-5-(trifluoromethyl)benzoyl)pyrrolidine-2-carboxylic acid
34 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-methoxyphenyl)-5-phenyl-1H-pyrazole-3-carbonyl)pyrrolidine-2-carboxylic acid
35 (2S,5R)-5-(2-chlorophenyl)-1-(4-isopropoxybenzoyl)pyrrolidine-2-carboxylic acid
36 (2S,5R)-5-(2-chlorophenyl)-1-(3-((3,5-dimethylisoxazol-4-yl)methoxy)-5-methoxybenzoyl)pyrrolidine-2-carboxylic acid
37 (2S,5R)-5-(2-chlorophenyl)-1-(2,3-dihydro-1H-indene-2-carbonyl)pyrrolidine-2-carboxylic acid
38 (2S,5R)-5-(2-chlorophenyl)-1-(3-methyl-5-(trifluoromethoxy)benzoyl)pyrrolidine-2-carboxylic acid
39 (2S,5R)-1-(3-(benzyloxy)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
40 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
41 (2S,5R)-5-(2-chlorophenyl)-1-(2-phenylpyrimidine-5-carbonyl)pyrrolidine-2-carboxylic acid
42 (2S,5R)-5-(2-chlorophenyl)-1-(4-(trifluoromethoxy)benzoyl)pyrrolidine-2-carboxylic acid
43 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
44 4-((2S,5R)-2-carboxy-5-(2-chlorophenyl)pyrrolidine-1-carbonyl)-2,6-dimethoxypyrimidin-1-ium formate
45 (2S,5R)-5-(2-chlorophenyl)-1-(4-phenylbutanoyl)pyrrolidine-2-carboxylic acid
46 (2S,5R)-5-(2-chlorophenyl)-1-(3-methyl-5-(trifluoromethyl)benzoyl)pyrrolidine-2-carboxylic acid
47 4 (2S,5R)-1-([1,1′-biphenyl]-4-carbonyl)-5-(3-chloropyridin-2-yl)pyrrolidine-2-carboxylic acid
48 (2S,5R)-5-(2-chlorophenyl)-1-(3-hydroxy-5-(trifluoromethyl)benzoyl)pyrrolidine-2-carboxylic acid
49 (2S,5S)-5-(2-chlorophenyl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
50 (2S,5R)-1-(3,5-dimethoxybenzoyl)-5-phenylpyrrolidine-2-carboxylic acid
51 (S)-5-([1,1′-biphenyl]-3-yl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
52 (2S,5R)-5-(2-chlorophenyl)-1-(3-phenylpropanoyl)pyrrolidine-2-carboxylic acid
53 (2S,5S)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
54 (2S,5R)-1-([1,1′-biphenyl]-4-carbonyl)-5-(pyridin-2-yl)pyrrolidine-2-carboxylic acid
55 (2S,5R)-5-(2-chlorophenyl)-1-(5-phenylpicolinoyl)pyrrolidine-2-carboxylic acid
57 (2S,5R)-5-(2-fluorophenyl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
59 (2R,5S)-1-([1,1′-biphenyl]-4-carbonyl)-5-phenylpyrrolidine-2-carboxylic acid
61 (2R,5S)-5-phenyl-1-(2-phenylacetyl)pyrrolidine-2-carboxylic acid
62 (2S,5R)-1-(3-methoxybenzoyl)-5-(2-methoxyphenyl)pyrrolidine-2-carboxylic acid
63 (2R,5S)-5-(2-chlorophenyl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
65 (2S)-5-(4-chlorophenyl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
66 (2S)-5-([1,1′-biphenyl]-4-yl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
67 (2S,5R)-methyl 5-(2-chlorophenyl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylate
69 (2S)-5-cyclohexyl-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
71 (2S,5S)-5-(2-chlorophenyl)-1-(3,5-dimethoxybenzoyl)pyrrolidine-2-carboxylic acid
72 (2S,5R)-5-([1,1′-biphenyl]-2-yl)-1-(3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
75 (2S,5R)-5-(2-chlorophenyl)-1-(6-phenylpyrimidine-4-carbonyl)pyrrolidine-2-carboxylic acid
76 (2S,5R)-5-(2-chlorophenyl)-1-(6-(2-fluorophenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
77 (2S,5R)-5-(2-chlorophenyl)-1-(6-(2-chlorophenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
78 (2S,5R)-5-(2-chlorophenyl)-1-(6-(2-methoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
79 (2S,5R)-5-(2-chlorophenyl)-1-(6-(3-fluorophenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
80 (2S,5R)-5-(2-chlorophenyl)-1-(6-(3-methoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
81 (2S,5R)-5-(2-chlorophenyl)-1-(6-(4-methoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
82 (2S,5R)-5-(2-chlorophenyl)-1-(6-(4-fluorophenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
83 (2S,5R)-5-(2-chlorophenyl)-1-(2-(2-chlorophenyl)pyrimidine-5-carbonyl)pyrrolidine-2-carboxylic acid
84 (2S,5R)-5-(2-chlorophenyl)-1-(2-methyl-6-phenylnicotinoyl)pyrrolidine-2-carboxylic acid
85 (2S,5R)-1-(4-chloro-2-(pyridin-3-yl)pyrimidine-5-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
86 (2S,5R)-1-(4-chloro-2-(pyridin-2-yl)pyrimidine-5-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
87 (2S,5R)-1-(4-chloro-2-(pyridin-4-yl)pyrimidine-5-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
88 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridin-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
89 (2S,5R)-1-(4-((4-chlorophenoxy)methyl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
90 (2S,5R)-5-(2-chlorophenyl)-1-(4-((4-fluorophenoxy)methyl)benzoyl)pyrrolidine-2-carboxylic acid
91 (2S,5R)-5-(2-chlorophenyl)-1-(4-((4-methoxyphenoxy)methyl)benzoyl)pyrrolidine-2-carboxylic acid
92 (2S,5R)-1-(4-((2-chlorophenoxy)methyl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
93 (2S,5R)-5-(2-chlorophenyl)-1-(4-((2-methoxyphenoxy)methyl)benzoyl)pyrrolidine-2-carboxylic acid
94 (2S,5R)-5-(2-chlorophenyl)-1-(4-((3-methoxyphenoxy)methyl)benzoyl)pyrrolidine-2-carboxylic acid
95 (2S,5R)-1-(4-((3-chlorophenoxy)methyl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
96 (2S,5R)-5-(2-chlorophenyl)-1-(4-((p-tolyloxy)methyl)benzoyl)pyrrolidine-2-carboxylic acid
97 (2S,5R)-5-(2-chlorophenyl)-1-(4-((3-methoxybenzyl)oxy)benzoyl)pyrrolidine-2-carboxylic acid
98 (2S,5R)-1-(4-((3-chlorobenzyl)oxy)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
99 (2S,5R)-5-(2-chlorophenyl)-1-(4-((3,5-dimethylisoxazol-4-yl)methoxy)benzoyl)pyrrolidine-2-carboxylic acid
100 (2S,5R)-5-(2-chlorophenyl)-1-(4-((3,5-dimethyl-1H-pyrazol-1-yl)methoxy)benzoyl)pyrrolidine-2-carboxylic acid
101 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridin-2-ylmethoxy)benzoyl)pyrrolidine-2-carboxylic acid
102 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridin-4-ylmethoxy)benzoyl)pyrrolidine-2-carboxylic acid
103 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridin-3-ylmethoxy)benzoyl)pyrrolidine-2-carboxylic acid
104 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-methyl-1H-pyrazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
105 (2S,5R)-5-(2-chlorophenyl)-1-(4-(isoxazol-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
106 (2S,5R)-1-(4-(4H-1,2,4-triazol-4-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
107 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
108 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-oxo-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
109 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
110 (2S,5R)-1-(4-(1H-pyrazol-1-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
111 (2S,5R)-5-(2-chlorophenyl)-1-(4-(oxazol-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
112 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3,5-dimethyl-1H-pyrazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
113 (2S,5R)-5-(2-chlorophenyl)-1-(2′,5′-dichloro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
114 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
115 (2S,5R)-5-(2-chlorophenyl)-1-(4-(furan-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
116 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
117 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3-fluoropyridin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
118 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
119 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-(dimethylamino)pyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
120 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
121 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-methylpyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
122 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
123 (2S,5R)-5-(2-chlorophenyl)-1-(4′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
124 (2S,5R)-5-(2-chlorophenyl)-1-(4′-cyano-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
125 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
126 (2S,5R)-1-(4′-chloro-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
127 (2S,5R)-1-(3′-chloro-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
128 (2S,5R)-1-(2′-chloro-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
129 (2S,5R)-5-(2-chlorophenyl)-1-(4′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
130 (2S,5R)-5-(2-chlorophenyl)-1-(3′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
131 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
132 (2S,5R)-5-(2-chlorophenyl)-1-(4-(naphthalen-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
133 (2S,5R)-5-(2-chlorophenyl)-1-(3′,5′-difluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
134 (2S,5R)-5-(2-chlorophenyl)-1-(2′-hydroxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
135 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(trifluoromethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
136 (2S,5R)-1-(2′-(benzyloxy)-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
137 (2S,5R)-5-(2-chlorophenyl)-1-(2′-phenoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
138 (2S,5R)-5-(2-chlorophenyl)-1-(2′-isopropoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
139 (2S,5R)-5-(2-chlorophenyl)-1-(2′-isobutoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
140 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(cyclopropylmethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
141 (2S,5R)-5-(2-chlorophenyl)-1-(2′-((4-fluorobenzyl)oxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
142 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-chloropyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
143 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-fluoropyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
144 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-chloropyridin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
145 (2S,5R)-1-(4-(2-chloro-3-fluoropyridin-4-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
146 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-chloropyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
147 (2S,5R)-1-(4-(6-(benzyloxy)pyridin-3-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
148 (2S,5R)-1-(4-(1H-pyrazol-4-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
149 (2S,5R)-5-(2-chlorophenyl)-1-(4-(thiophen-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
150 (2S,5R)-5-(2-chlorophenyl)-1-(4-cyclohexylbenzoyl)pyrrolidine-2-carboxylic acid
151 (2S,5R)-5-(2-chlorophenyl)-1-(4′-(methylsulfonyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
153 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(methylsulfonyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
154 (2S,5R)-5-(2-chlorophenyl)-1-(4-(tetrahydro-2H-pyran-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
156 (2S,5R)-5-(2-chlorophenyl)-1-(4-phenoxybenzoyl)pyrrolidine-2-carboxylic acid
157 (2S,5R)-1-(4-benzylbenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
158 (2S,5R)-1-(4-benzoylbenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
159 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyrimidin-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
160 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4,6-dimethoxypyrimidin-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
161 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,4-dimethoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
162 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
163 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-(dimethylamino)pyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
164 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-morpholinopyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
165 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-(piperidin-1-yl)pyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
168 (2S,5R)-5-(2-chlorophenyl)-1-(cyclohexanecarbonyl)pyrrolidine-2-carboxylic acid
169 (2S,5R)-5-(2-chlorophenyl)-1-(4-methylpentanoyl)pyrrolidine-2-carboxylic acid
172 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4-methylpiperidin-1-yl)-3-nitrobenzoyl)pyrrolidine-2-carboxylic acid
173 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-oxopiperidin-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
174 (2S,5R)-5-(2-chlorophenyl)-1-(3-methyl-4-morpholinobenzoyl)pyrrolidine-2-carboxylic acid
175 (2S,5R)-5-(2-chlorophenyl)-1-(4-(piperidin-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
176 (2S,5R)-5-(2-chlorophenyl)-1-(4-morpholinobenzoyl)pyrrolidine-2-carboxylic acid
177 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-cyanophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
178 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4-chlorophenyl)cyclohexanecarbonyl)pyrrolidine-2-carboxylic acid
179 (2S,5R)-5-(2-chlorophenyl)-1-(4-phenylcyclohexanecarbonyl)pyrrolidine-2-carboxylic acid
184 (2R,5S)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
189 (2S,5R)-5-(2-chlorophenyl)-1-(6-(2-fluorophenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
191 (2S,5R)-5-(2-chlorophenyl)-1-(5-methoxy-6-phenylnicotinoyl)pyrrolidine-2-carboxylic acid
192 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methoxyphenoxy)benzoyl)pyrrolidine-2-carboxylic acid
193 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3-methoxypyridin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
194 (2S)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-4,4-dimethylpyrrolidine-2-carboxylic acid
195 (2S)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-4-methylpyrrolidine-2-carboxylic acid
196 (2S,5R)-5-(2-chlorophenyl)-1-(2-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
197 (2S,5R)-5-(2-chlorophenyl)-1-(2′-cyano-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
198 (2S,5R)-5-(2-chlorophenyl)-1-(2′,6′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
199 (2S,5R)-5-(2-chlorophenyl)-1-(2′,4′-dichloro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
200 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(trifluoromethyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
201 (2S,5R)-5-(2-chlorophenyl)-1-(2,2′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
202 (2S,5R)-1-(4′-chloro-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
203 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4-methoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
204 (2S,5R)-5-(2-chlorophenyl)-1-(2′,4′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
205 (2S,5R)-1-([1,1′-biphenyl]-4-carbonyl)-5-(pyridin-3-yl)pyrrolidine-2-carboxylic acid
206 (2R,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
207 (2S,5R)-5-(2-chlorophenyl)-1-(1-phenyl-1H-benzo[d]imidazole-5-carbonyl)pyrrolidine-2-carboxylic acid
208 (2S,5R)-methyl 5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylate
211 (2S,4S,5R)-5-(2-chlorophenyl)-4-(hydroxymethyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
217 (2S,4S,5S)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-4-(phenylsulfonyl)pyrrolidine-2-carboxylic acid
220 (2S,5R)-5-(2-chlorophenyl)-4-cyano-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
221 (2S,3R,5R)-5-(2-chlorophenyl)-3-cyano-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
224 (2S,5R)-1-(2-chloro-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
225 (2S,5R)-1-(2′-chloro-2-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
226 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(2-methoxyethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
227 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methylthiophen-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
228 (2S,5R)-5-(2-chlorophenyl)-1-(2′,6′-dichloro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
229 (2S,5R)-1-(2′-chloro-4′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
230 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(pyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
231 (2S,5R)-1-(2′-carbamimidoyl-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
232 (2S,5R)-5-(2-fluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
233 (2S,5R)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(o-tolyl)pyrrolidine-2-carboxylic acid
234 (2S,5R)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-methoxyphenyl)pyrrolidine-2-carboxylic acid
235 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(methoxymethyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
236 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
237 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(2-methoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
238 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-methoxypyrazin-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
239 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-(2-methoxyethoxy)pyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
240 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3-methoxypyrazin-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
241 (2S,5R)-1-(4-(2-chloro-4-(dimethylamino)pyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
242 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyrimidin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
243 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(dimethylamino)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
244 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methoxypyrimidin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
245 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(2-methoxypyrimidin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
246 (2S,5R)-5-(2-fluorophenyl)-1-(4-(2-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
247 (2S,5R)-1-(4-(2,4-dimethoxypyrimidin-5-yl)benzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
248 (2S,5R)-5-(2-chlorophenyl)-1-(2-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
249 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
251 (2S,5R)-5-(2-chlorophenyl)-1-(5-phenylpyrazine-2-carbonyl)pyrrolidine-2-carboxylic acid
252 (2S,5R)-5-(2-chlorophenyl)-1-(5-methoxy-6-(2-methoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
253 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-methoxypyrimidin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
254 (2S,5R)-5-(2-chlorophenyl)-1-(4-(pyridazin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
255 (2S,5R)-1-(4-(1H-1,2,3-triazol-1-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
256 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
257 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-methoxyphenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
258 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methoxyphenyl)piperazine-1-carbonyl)pyrrolidine-2-carboxylic acid
259 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-methoxypyrimidin-5-yl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
260 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4-methoxypyrimidin-5-yl)piperazine-1-carbonyl)pyrrolidine-2-carboxylic acid
261 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(4-methylpiperidin-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
262 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(1-methylpiperidin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
263 (2S,5R)-5-(2-chlorophenyl)-1-(2-cyano-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
264 (2S,5R)-5-(2-chlorophenyl)-1-(2-isobutoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
265 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,4-dichloropyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
266 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,4-dimethoxypyrimidin-5-yl)-3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
267 (2S,5R)-1-(4-(2-chloro-4-methoxypyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
268 (2S,3S,5S)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-3-methylpyrrolidine-2-carboxylic acid
269 (2S,5R)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
270 (2S,5R)-1-(2′-(2-amino-2-oxoethoxy)-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
271 (2S,5R)-5-(2-chlorophenyl)-1-(2-(cyclopropylmethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
272 (2S,5R)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-phenylpyrrolidine-2-carboxylic acid
273 (2S,5R)-5-(3-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
274 (2S,5R)-5-(4-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
275 (2S,5R)-5-(3-fluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
276 (2S,5R)-5-(4-fluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
278 (2S,5R)-4-acetyl-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
279 (2S,4S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-4-(methoxymethyl)pyrrolidine-2-carboxylic acid
280 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2-methoxypyrimidin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
281 (2S,5R)-5-cyclohexyl-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
283 (2S,5R)-1-(4-(2-chloro-4-methoxypyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
284 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3-methoxypyridin-2-yl)benzoyl)pyrrolidine-2-carboxylic acid
285 (2R,5R)-5-(2-fluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
286 (2S,5S)-5-(2-fluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
287 (2R,5S)-5-(2-fluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
288 (2S,5R)-5-(2-chlorophenyl)-1-(2-(trifluoromethyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
289 (2S,5R)-5-(2-chlorophenyl)-1-(2′,4′-difluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
290 (2S,5R)-5-(2-chlorophenyl)-1-(2-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
291 (2S,5R)-5-(2,6-difluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
292 (2S,5R)-5-(2,4-difluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
293 (2S,5R)-5-(2,4-dichlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
294 (2S,5R)-5-isobutyl-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
295 (2S,5R)-5-isopropyl-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
296 (2S,5R)-1-(3-chloro-4-(pyrimidin-4-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
297 (2S,5R)-5-(2-chlorophenyl)-1-(2-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
298 (2S,5R)-5-(2-chlorophenyl)-1-(2′-fluoro-4′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
299 (2S,5R)-5-(2-chlorophenyl)-1-(4′-fluoro-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
300 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-ethoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
301 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-isopropoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
302 (2S,5R)-5-(2-chlorophenyl)-1-(4-(6-methoxy-2-methylpyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
303 (2S,5R)-1-(3-chloro-4-(2-methoxypyrimidin-4-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
304 (2S,5R)-1-(3-chloro-4-(pyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
305 (2S,5R)-5-(2-chlorophenyl)-4-cyano-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-3-methylpyrrolidine-2-carboxylic acid
306 (2S,4S,5R)-5-(2-chlorophenyl)-4-cyano-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-4-methylpyrrolidine-2-carboxylic acid
307 (2S,5R)-5-(2-chlorophenyl)-1-(2′,3′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
308 (2S,5R)-5-(2-chlorophenyl)-1-(3′,4′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
309 (2S,5R)-5-(2-chlorophenyl)-1-(2′,3′,4′-trimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
310 (2S,5R)-5-(2-chlorophenyl)-1-(2′,3′,6′-trimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
311 (2S,5R)-5-(2-chlorophenyl)-1-(3′,5 ‘-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
312 (2S,5R)-5-(2-chlorophenyl)-1-(2’,5′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
313 (2S,5R)-5-(2-chlorophenyl)-1-(2′-isopropyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
314 (2S,5R)-1-(2,2′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
315 (2S,5R)-1-(2-fluoro-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
316 (2S,5R)-5-(2-chlorophenyl)-1-(2-fluoro-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
318 (2S,5R)-5-cyclopentyl-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
319 (2S,5R)-5-(2-chlorophenyl)-1-(2′-ethyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
320 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethylpyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
321 (2S,5R)-1-(4-(2,4-bis(benzyloxy)pyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
322 (2S,5R)-1-([1,1′:4′,1″-terphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
323 (2S,5R)-5-(2-chlorophenyl)-1-(4′-propyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
324 (2S,5R)-1-(4′-(tert-butyl)-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
325 (2S,5R)-1-(3-chloro-4-(2,4-dimethoxypyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
326 (2S,5R)-5-(2-chlorophenyl)-1-(5-(2-methoxyphenyl)pyrazine-2-carbonyl)pyrrolidine-2-carboxylic acid
327 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(4-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
328 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(6-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
329 (2S,5R)-1-(3-chloro-4-(2-methoxypyrimidin-5-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
330 (2S,5R)-1-(3-chloro-4-(6-methoxypyridin-3-yl)benzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
331 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-(4-chlorophenyl)thiazol-2-yl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
332 (2S,5R)-5-(2-fluorophenyl)-1-(5-methoxy-6-(2-methoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
333 (2S,5R)-1-(1-(benzo[d]oxazol-2-yl)piperidine-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
334 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(pyrrolidin-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
335 (2S,5R)-5-(2-chlorophenyl)-1-(5-methoxy-6-(2-methoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
336 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-methoxyphenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
337 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,4-dimethoxypyrimidin-5-yl)-3-methoxybenzoyl)pyrrolidine-2-carboxylic acid
338 (2S,5R)-5-(2-bromophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
339 (2S,5R)-5-(2-chlorophenyl)-1-(3′-cyano-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
340 (2S,5R)-5-(2-chlorophenyl)-1-(3′-cyano-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
341 (2S,5R)-5-(2-chlorophenyl)-1-(3′-cyano-2′,4′-bis(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
342 (2S,5R)-1-(3′-amino-2′-methyl-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
343 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methyl-3′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
344 (2S,5R)-1-(3′-acetamido-2′-methyl-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
345 (2S,5R)-5-(2-chlorophenyl)-1-(5′-cyano-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
346 (2S,5R)-5-(2-chlorophenyl)-1-(5′-cyano-2′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
347 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4,6-dimethoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
348 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3,6-dimethoxypyridazin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
349 (2S,5S)-5-isopentyl-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
350 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-4′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
351 (2S,5R)-1-(4′-acetamido-2′-methoxy-[1, 1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
352 (2S,5R)-1-(3′-carbamimidoyl-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
353 (2S,5R)-5-(2-chlorophenyl)-1-(3′-((E)-N′-hydroxycarbamimidoyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
354 (2S,5R)-5-(2-fluorophenyl)-1-(2′-methoxy-4′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
355 (2S,5R)-5-(2,4-difluorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
356 (2S,5R)-5-(2-chlorophenyl)-1-(3-methoxy-4-(5-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
357 (2S,5R)-1-(4′-amino-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
358 (2S,5R)-5-(2-chlorophenyl)-1-(2′,3,6′-trimethoxy-[2,3′-bipyridine]-5-carbonyl)pyrrolidine-2-carboxylic acid
359 (2S,5R)-1-(3′-carbamoyl-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
360 (2S,5R)-5-(2-chlorophenyl)-1-(5′-cyano-2′,3′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
361 (2S,5R)-5-(2-chlorophenyl)-1-(2′-cyano-4′,5′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
362 (2S,5R)-5-(2-chlorophenyl)-1-(3′,4′,5′-trimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
363 (2S,5R)-5-(2-chlorophenyl)-1-(2′-(cyanomethyl)-4′,5′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
364 (2S,5R)-5-(2-chlorophenyl)-1-(3′,4′-dicyano-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
365 (2S,5R)-5-(2-chlorophenyl)-1-(5′-cyano-2′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
366 (2S,5R)-5-(2-chlorophenyl)-1-(2-fluoro-3′,4′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
367 (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)-3-fluorobenzoyl)pyrrolidine-2-carboxylic acid
368 (2S,5R)-5-(2-chlorophenyl)-1-(3-fluoro-4-(6-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
369 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-cyano-4-(trifluoromethyl)phenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
370 (2S,5R)-1-(1-(2-chloro-4-(trifluoromethyl)phenyl)piperidine-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
371 (2S,5R)-1-(5′-cyano-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
372 (2S,5R)-1-(4-(2,6-dimethoxypyridin-3-yl)-3-fluorobenzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
373 (2S,5R)-1-(3-fluoro-4-(6-methoxypyridin-3-yl)benzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
374 (2S,5R)-1-(4-(3,6-dimethoxypyridazin-4-yl)benzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
375 (2S,5R)-1-(3′-carbamoyl-4′-cyano-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
376 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
377 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-(morpholinosulfonyl)-2-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
378 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-nitro-4-(piperidin-1-ylsulfonyl)phenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
379 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-(N,N-diethylsulfamoyl)-2-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
380 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-methyl-2-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
381 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-cyano-4-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
382 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
383 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-fluoro-4-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
384 (2S,5R)-5-(2-chlorophenyl)-1-(1-(3-methoxy-4-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
385 (2S,5R)-1-(1-(5-chloro-2-nitrophenyl)piperidine-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
386 (2S,5R)-5-(2-cyanophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
387 (2S,5R)-5-(2-chlorophenyl)-1-(2′-cyano-4′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
388 (2S,5R)-5-(2-chlorophenyl)-1-(2-fluoro-4′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
389 (2S,5R)-5-(2-chlorophenyl)-1-(2-fluoro-3′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
390 (2S,5R)-5-(2-chlorophenyl)-1-(2′-cyano-2-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
391 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-cyano-4-(methylsulfonamido)phenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
392 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-cyano-4-methoxyphenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
393 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-(methylsulfonamido)-4-(trifluoromethyl)phenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
394 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-nitrophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
395 (2S,5R)-5-(2-chlorophenyl)-1-(1-(4-cyanophenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
396 (2S,5R)-5-(3,5-difluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
397 (2S,5R)-5-(3,4-difluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
398 (2S,5R)-5-(2,3-difluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
399 (2S,5R)-5-(2,5-difluorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
400 (2S,5R)-5-([1,1′-biphenyl]-2-yl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
401 (2S,5R)-1-(2′-cyano-4′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
402 (2S,5R)-5-(4-cyanophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
403 (2S,5R)-5-(2-chlorophenyl)-1-(4-(5-methyl-4-(phenylsulfonyl)-1H-1,2,3-triazol-1-yl)benzoyl)pyrrolidine-2-carboxylic acid
404 (2S,5R)-5-(2-chlorophenyl)-1-(3′-cyano-4′-fluoro-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
405 (2S,5R)-1-(2′-chloro-5′-cyano-[1,1′-biphenyl]-4-carbonyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid
406 (2S,5R)-5-(2-chlorophenyl)-1-(2′-cyano-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
407 (2S,5R)-5-(2-chlorophenyl)-1-(1-(2-methoxy-4-(trifluoromethyl)phenyl)piperidine-4-carbonyl)pyrrolidine-2-carboxylic acid
408 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methyl-3′-(N-methylmethylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
409 (2S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-4′-(N-methylmethylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
410 (2S,5R)-5-(2-chlorophenyl)-1-(6-(5-cyano-2-methoxyphenyl)-5-methoxynicotinoyl)pyrrolidine-2-carboxylic acid
411 (2S,5R)-5-(2-chlorophenyl)-1-(6-(2,4-dimethoxyphenyl)-5-methoxynicotinoyl)pyrrolidine-2-carboxylic acid
412 (2S,5R)-5-(2-chlorophenyl)-1-(6-(2,4-dimethoxyphenyl)nicotinoyl)pyrrolidine-2-carboxylic acid
413 (2S,5R)-1-(2′-cyano-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
414 (2S,5R)-1-(3′-cyano-4′-fluoro-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
415 (2S,5R)-1-(2′-chloro-5′-cyano-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
416 (2S,5R)-5-(2-chlorophenyl)-1-(4-(3,6-dimethoxypyridazin-4-yl)-3-fluorobenzoyl)pyrrolidine-2-carboxylic acid
417 (2S,5R)-5-(2-fluorophenyl)-1-(2′-methyl-3′-(N-methylmethylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
418 (2S,5R)-5-(2-fluorophenyl)-1-(2′-methoxy-4′-(N-methylmethylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
419 (2S,5R)-5-(2-chlorophenyl)-1-(4-(4,6-dimethoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
420 (2S,5R)-5-(2,3-difluorophenyl)-1-(4-(2,4-dimethoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
421 (2S,5R)-1-(5′-cyano-2′-methyl-[1,1′-biphenyl]-4-carbonyl)-5-(2,3-difluorophenyl)pyrrolidine-2-carboxylic acid
422 (2S,5R)-5-(2,3-difluorophenyl)-1-(2′-methoxy-4′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
423 (2S,5R)-5-(2,3-difluorophenyl)-1-(2′-methyl-3′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
424 (2S,5R)-5-(2-fluorophenyl)-1-(2′-methyl-3′-(methylsulfonamido)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid
425 (2S,5R)-5-(2,3-difluorophenyl)-1-(4-(2-methoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid
426 (2S,5R)-5-(2,3-difluorophenyl)-1-(3-methoxy-4-(2-methoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
427 (2S,5R)-5-(2-fluorophenyl)-1-(3-methoxy-4-(2-methoxypyrimidin-5-yl)benzoyl)pyrrolidine-2-carboxylic acid
428 (2S,5R)-5-(2,3-difluorophenyl)-1-(4-(3,6-dimethoxypyridazin-4-yl)benzoyl)pyrrolidine-2-carboxylic acid
429 (2S,5R)-1-(5′-cyano-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)-5-(2,3-difluorophenyl)pyrrolidine-2-carboxylic acid
430 (2S,5R)-1-(5′-cyano-2′-methyl-[1,1′-biphenyl]-4-carbonyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid
431 (2S,5R)-5-(2,3-difluorophenyl)-1-(4-(3,6-dimethoxypyridazin-4-yl)-3-fluorobenzoyl)pyrrolidine-2-carboxylic acid; and
432 (2S,5R)-1-(4-(3,6-dimethoxypyridazin-4-yl)-3-fluorobenzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid;
or a pharmaceutically acceptable salt thereof.
21. The method according to claim 1 for delaying in a patient the onset of an inflammatory disease.
22. The method according to claim 1 , wherein the inflammatory disease is selected from the group consisting of rheumatoid arthritis; inflammatory bowel disease (IBD) including but not limited to Crohn's disease, ulcerative colitis and colitis; Pagets disease; osteoporosis; multiple myeloma; uveitis; acute myelogenous leukemia, chronic myelogenous leukemia; pancreatic β cell destruction; rheumatoid spondylitis; osteoarthritis; gouty arthritis and other arthritis conditions; gout; adult respiratory distress syndrome (ARDS); chronic pulmonary inflammatory disease; silicosis; pulmonary sarcoidosis; psoriasis; rhinitis; anaphylaxis; contact dermatitis; pancreatitis; asthma; muscle degeneration; cachexia such as cachexia secondary to infection or malignancy, cachexia secondary to acquired immune deficiency syndrome; Reiter's syndrome; type I diabetes; bone resorption disease; graft vs. host reaction; ischemia reperfusion injury; brain trauma; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; endotoxic shock; gram negative sepsis; fever and myalgias due to infection such as influenza; pyrosis.
23. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
24. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(2′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
25. The method according to claim 1 , wherein the compound is (2S,5R)-1-(3-((4-chlorobenzyl)oxy)-5-methoxybenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
26. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(2′-(trifluoromethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
27. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(2′-(cyclopropylmethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
28. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
29. The method according to claim 1 , wherein the compound is (2S,5R)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
30. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(2′,5′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
31. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(5′-cyano-2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
32. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(5′-cyano-2′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
33. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(2-fluoro-3′,4′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
34. The method according to claim 1 , wherein the compound is (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)-3-fluorobenzoyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
35. The method according to claim 1 , wherein the compound is (2S,5R)-1-(4-(2,6-dimethoxypyridin-3-yl)-3-fluorobenzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
36. The method according to claim 1 , wherein the compound is (2S,5R)-1-(5′-cyano-2′-methyl-[1,1′-biphenyl]-4-carbonyl)-5-(2,3-difluorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.