Substituted pyrrolidines as G-protein coupled receptor 43 agonists
The present invention is directed to novel pyrrolidine carboxylic acid derivatives, pharmaceutical compositions, and their use in treating and/or preventing metabolic diseases as agonists of g-protein coupled receptor 43.
1. A compound of formula:
and pharmaceutically acceptable salts thereof, wherein
R 1 and R 2 are H;
D is C═O;
L 2 is a single bond;
R is H, linear or branched alkyl, or aryl;
Ar 1 is (5-6)-membered aryl, (5-6)-membered heteroaryl, C 3 -C 6 cycloalkyl, or linear or branched C 3 -C 6 alkyl, each of which being optionally substituted by one or more group(s) selected from halo, cyano, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, hydroxy, 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, hydroxy, alkoxy, and haloalkoxy;
Ar 2 is aryl, heteroaryl, piperidinyl, piperazinyl or cycloalkyl, 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, hydroxy, 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 and oxo, wherein each of said substituent group(s) may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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; or
two Ar 2 substituents form an alkylenedioxy group or a haloalkylenedioxy group, wherein each of said alkylenedioxy or haloalkylenedioxy groups may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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; or
fused to the Ar 2 cycloalkyl group may be one or more aryl or heteroaryl moieties, wherein each of said aryl or heteroaryl moieties may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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 or C 1 -C 4 alkyl;
under the condition that the compound 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,
(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,
1-[7-(4-tert-butyl-phenoxy)-1-cyclopentylmethyl-isoquinoline-3-carbonyl]-(5R)-phenyl-pyrrolidine-(2S)-carboxylic acid,
and further 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 monosubstituted hydroxymethyl.
2. The compound according to claim 1 having the formula Ib-1b′:
and pharmaceutically acceptable salts thereof.
3. The compound according to claim 2 having the formula Ib-1d:
and pharmaceutically acceptable salts thereof.
4. The compound according to claim 3 having the formula Ib-1e:
and pharmaceutically acceptable salts thereof, wherein
R 8 , R 8′ , R 9 , R 9′ and R 10 are independently selected from H, halo, cyano, alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, hydroxy, haloalkoxy, alkylamino, alkoxycarbonyl, alkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, haloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino, 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, hydroxy, alkoxy, and haloalkoxy.
5. The compound according to claim 4 having the formula Ib-1g:
and pharmaceutically acceptable salts thereof, wherein
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, hydroxy, 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 and heteroarylsulfonylamino, wherein each of said substituent group(s) may be optionally substituted by one or more further substituents selected from halo, cyano, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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, arylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino and oxo; 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′ , together with the phenyl group they are attached to, form an alkylenedioxy group or a haloalkylenedioxy group, wherein each of said alkylenedioxy or haloalkylenedioxy groups may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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; 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′ , together with the phenyl group they are attached to, form an aryl or heteroaryl moiety, wherein each of said aryl or heteroaryl moieties may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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.
6. The compound according to claim 5 having the formula Ib-1g1:
and pharmaceutically acceptable salts thereof.
7. The compound according to claim 6 having the formula Ib-1g1a:
and pharmaceutically acceptable salts thereof, wherein
R 17 , R 17′ , R 18′ and R 19 are independently selected from H, halo, cyano, alkyl, haloalkyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl, heteroaryl, heteroalkyl, hydroxy, alkoxy, alkoxyalkyl, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aryloxy, aralkyloxy, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino and haloalkylsulfonylamino.
8. The compound according to claim 5 having the formula Ib-1g2:
and pharmaceutically acceptable salts thereof.
9. The compound according to claim 5 having the formula Ib-1h:
and pharmaceutically acceptable salts thereof, wherein
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 groups selected from fluoro or methyl; and
R 13 , R 13′ , R 14 , R 14′ and R 15 are independently selected from H, halo, cyano, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl, heteroaryl, heteroalkyl, hydroxy, alkoxy, alkoxyalkyl, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aralkyloxy optionally substituted by a fluoro group, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino and haloalkylsulfonylamino.
10. The compound according to claim 9 having the formula Ib-1h1:
and pharmaceutically acceptable salts thereof.
11. The compound according to claim 5 having the formula Ib-1h′:
and pharmaceutically acceptable salts thereof, wherein
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, hydroxyalkyl, haloalkyl, hydroxy, alkoxy, alkoxyalkyl, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aralkyloxy, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylamino, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino and haloalkylsulfonylamino.
12. The compound according to claim 5 having the formula Ib-1h″:
and pharmaceutically acceptable salts thereof, wherein
the combination of R 8 and R 9 is selected from (i) F and H, (ii) Cl and H, or (iii) F and 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 combination 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 23 or 24:
Combination
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-OCH 3
CH
N
CH
CH.
13. The compound according to claim 5 having the formula Ib-1i:
and pharmaceutically acceptable salts thereof.
14. The compound according to claim 4 having the formula Ib-1j:
and pharmaceutically acceptable salts thereof, wherein
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 groups 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, hydroxy, 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 and heteroarylsulfonylamino, wherein each of said substituent group(s) may be optionally substituted by one or more further substituents selected from halo, cyano, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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, arylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino, haloalkylsulfonylamino and oxo; or
R 12′ and R 11′ , together with the pyridinyl group they are attached to, form an alkylenedioxy group or a haloalkylenedioxy group, wherein each of said alkylenedioxy or haloalkylenedioxy groups may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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; or
R 12′ and R 11′ , together with the pyridinyl group they are attached to, form an aryl or heteroaryl moiety, wherein each of said aryl or heteroaryl moieties may be optionally substituted by one or more further substituents selected from halo, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl optionally substituted by a chloro or methyl group, heteroaryl, heteroalkyl, hydroxy, 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; and
R 13 , R 13′ , R 14 , R 14′ and R 15 are independently selected from H, halo, cyano, alkyl, hydroxyalkyl, haloalkyl, cyanomethyl, cycloalkyl, heterocyclyl, C 5 -C 12 aryl, heteroaryl, heteroalkyl, hydroxy, alkoxy, alkoxyalkyl, alkoxyalkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aralkyloxy optionally substituted by a fluoro group, amino, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyloxy, alkylcarbamoylamino, carbamimidoyl, hydroxycarbamimidoyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, sulfamoyl, alkylsulfamoyl, alkylsulfonylamino and haloalkylsulfonylamino.
15. The compound according to claim 4 having the formula Ib-1k:
and pharmaceutically acceptable salts thereof, wherein
R 12′ is selected from H, fluoro, chloro, methyl, trifluoromethyl or methoxy; and
R 17 , R 17′ , R 18′ and R 19 are independently selected from H, halo, cyano, nitro, alkyl, haloalkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, haloalkoxy, cycloalkylalkyloxy, amino, alkylcarbonylamino, alkylsulfonyl and alkylsulfonylamino.
16. The compound according to claim 4 having the formula Ib-1l:
and pharmaceutically acceptable salts thereof, wherein
R 20 is aryl or heteroaryl, wherein each of said aryl or heteroaryl may be optionally substituted by one or more substituent(s) selected from halo, alkyl, haloalkyl, cyano, nitro, phenyl optionally substituted by a chloro, alkoxy, heterocyclylsulfonyl, alkylsulfamoyl and alkylsulfonylamino.
17. The compound according to claim 1 having the formula Ic-1b′:
and pharmaceutically acceptable salts thereof.
18. The compound according to claim 1 having the formula Id-1b′:
and pharmaceutically acceptable salts thereof.
19. The compound according to claim 1 having the formula Ie-1b′:
and pharmaceutically acceptable salts thereof.
20. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(2′-methoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
21. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(2′-methyl-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
22. The compound according to claim 1 being (2S,5R)-1-(3-((4-chlorobenzyl)oxy)-5-methoxybenzoyl)-5-(2-chlorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
23. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(2′-(trifluoromethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
24. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(2′-(cyclopropylmethoxy)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
25. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
26. The compound according to claim 1 being (2S,5R)-1-(4-(2,6-dimethoxypyridin-3-yl)benzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
27. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(2′,5′-dimethoxy-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
28. The compound according to claim 1 being (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.
29. The compound according to claim 1 being 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.
30. The compound according to claim 1 being (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.
31. The compound according to claim 1 being (2S,5R)-5-(2-chlorophenyl)-1-(4-(2,6-dimethoxypyridin-3-yl)-3-fluorobenzoyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
32. The compound according to claim 1 being (2S,5R)-1-(4-(2,6-dimethoxypyridin-3-yl)-3-fluorobenzoyl)-5-(2-fluorophenyl)pyrrolidine-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
33. The compound according to claim 1 being (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.
34. The compound according to claim 1 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;
46 (2S,5R)-5-(2-chlorophenyl)-1-(3-methyl-5-(trifluoromethyl)benzoyl)pyrrolidine-2-carboxylic acid;
47 (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;
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;
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;
64 (2R,5R)-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-chiorophenyl)-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-chiorophenyl)-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;
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.
35. A medicament comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
36. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant.