ARYL GPR120 RECEPTOR AGONISTS AND USES THEREOF
Aryl GPR120 agonists are provided. These compounds are useful for the treatment of metabolic diseases, including Type II diabetes and diseases associated with poor glycemic control.
1 . A compound of Formula (A)
or a pharmaceutically acceptable salt thereof, wherein:
represents a 5-10 membered monocyclic or bicyclic aryl group, a 5-10 membered monocyclic or bicyclic heteroaryl group, a 5-10 membered monocyclic or bicyclic cycloalkyl group, a 5-10 membered monocyclic or bicyclic heterocycloalkyl group, or a 8-10 membered bicyclic group wherein an aryl or a 5-6 membered heteroaryl ring is fused to a 5-6 membered cycloalkyl or heterocycloalkyl ring;
E 1 , E 2 and E 3 are independently selected from the group consisting of C, N and S;
E 4 is selected from the group consisting of C and N;
X is selected from the group consisting of —CH 2 —, —C(O)— and —C(O)CH 2 —;
Y is selected from the group consisting of —CH 2 —, —NH— and —O—;
Z is selected from the group consisting of a —(CR 4 R 5 ) n —, —S—, —C(O)— and —CR 4 ═CR 5 —;
V is selected from the group consisting of a bond, —(CR 4 R 5 ) n —, —CR 4 ═CR 5 —, and —O—CR 4 R 5 —;
W is selected from the group consisting of H, C 1-6 alkyl and substituted C 1-6 alkyl;
R 1 is independently selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, CN, —OR a , —NR a R b , —C(O)R a , —C(O)OR a , —NR a C(O)R b , —S(O)R a and —S(O) 2 R a ;
R 2 is independently selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, aryloxy, -substituted aryloxy, CN, —OR a , —NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR a C(O)R b , —S(O)R a and —S(O) 2 R a ;
each of R a and R b is independently selected from the group consisting of H, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R 4 is independently selected from the group consisting of H, halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 1-6 alkoxy and substituted C 1-6 alkoxy;
R 5 is independently selected from the group consisting of H, halo, C 1-6 alkyl, substituted C 1-6 alkyl and C 1-6 alkoxy;
R 6 is selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 1-6 alkoxy, substituted C 1-6 alkoxy, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
optionally R 4 and R 5 cyclize to form a C 3-7 saturated ring or a spiro C 3-7 cycloalkyl group;
the subscript b is 0, 1, 2, 3 or 4;
the subscript g is 0, 1 or 2; and
the subscript n is independently 1, 2 or 3.
2 . The compound of claim 1 , wherein: X is —CH 2 —; Y is —O—; Z is —(CR 4 R 5 ) n ; and V is a bond.
3 . The compound of claim 2 , wherein Q is selected from the group consisting of
wherein A 1 , A 2 , A 3 and A 4 are independently selected from the group consisting of C and N, with the proviso that only 0, 1 or 2 of A 1 , A 2 , A 3 and A 4 is N and R 1 and subscript b are as previously defined.
4 . The compound of claim 1 of Formula (B)
or a pharmaceutically acceptable salt thereof, wherein:
A 1 , A 2 , A 3 and A 4 are independently selected from the group consisting of C and N, with the proviso that only 0, 1 or 2 of A 1 , A 2 , A 3 and A 4 is N;
J 1 , J 2 , J 3 , J 4 and J 5 are independently selected from the group consisting of N and C, with the proviso that only 0, 1 or 2 of J 1 , J 2 , J 3 , J 4 and J 5 is N;
each R 3 is independently selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, cyano, —OR a , —NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR a C(O)R b , —SR a , —S(O)R a and —S(O) 2 R a ;
the subscript c is 0, 1, 2 or 3; and
E 1 , E 2 , E 3 , E 4 , R 1 , R 2 , Z, V, R a , R b , subscript b and subscript g are as previously defined.
5 . The compound of claim 4 , wherein Z and V taken together are selected from the group consisting of
6 . The compound of claim 5 , wherein E 1 and E 2 are both C; and E 3 and E 4 are both N.
7 . The compound of claim 6 , wherein A 1 , A 2 , A 3 and A 4 are all C, and J 1 , J 2 , J 3 , J 4 and J 5 are all C.
8 . The compound of claim 7 , wherein the subscript g is 0 or 1; the subscript c is 0 or 1; and the subscript b is 0, 1 or 2.
9 . The compound of claim 8 , wherein R 1 is halo, C 1-3 alkyl or CF 3 ; g is 0 or g is 1 and R 2 is CH 3 ; and R 3 is C 1-4 alkyl or halo.
10 . A compound of Formula (C)
or a pharmaceutically acceptable salt thereof, wherein:
represents a 5-10 membered monocyclic or bicyclic aryl group, a 5-10 membered monocyclic or bicyclic heteroaryl group, a 5-10 membered monocyclic or bicyclic cycloalkyl group, a 5-10 membered monocyclic or bicyclic heterocycloalkyl group, or a 8-10 membered bicyclic group wherein an aryl or a 5-6 membered heteroaryl ring is fused to a 5-6 membered cycloalkyl or heterocycloalkyl ring;
E 1 , E 2 and E 3 are independently selected from the group consisting of C, N and O;
X is selected from the group consisting of —CH 2 — and —C(O)CH 2 —;
Y is selected from the group consisting of —CH 2 — and —O—;
Z is selected from the group consisting of —(CR 4 R 5 ) n —, —S—, —C(O)—, and —CR 4 ═CR 5 —;
V is selected from the group consisting of a bond, —(CR 4 R 5 ) n —, —CR 4 ═CR 5 —, and —O—CR 4 R 5 —;
W is selected from the group consisting of H, C 1-6 alkyl and substituted C 1-6 alkyl;
R 1 is independently selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, CN, —OR a , —NR a R b , —C(O)R a , —C(O)OR a , —NR a C(O)R b , —SR a , —S(O)R a and —S(O) 2 R a ;
R 2 is independently selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, aryloxy, -substituted aryloxy, CN, —OR a , —NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR a C(O)R b , —SR a , —S(O)R a and —S(O) 2 R a ;
each of R a and R b is independently selected from the group consisting of H, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R 4 is independently selected from the group consisting of H, halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 1-6 alkoxy and substituted C 1-6 alkoxy;
R 5 is independently selected from the group consisting of H, halo, C 1-6 alkyl, substituted C 1-6 alkyl and C 1-6 alkoxy;
optionally R 4 and R 5 cyclize to form a C 3-7 saturated ring or a spiro C 3-7 cycloalkyl group;
R 6 is selected from the group consisting of aryl, substituted aryl, heteroaryl and substituted heteroaryl;
the subscript b is 0, 1, 2, 3 or 4;
the subscript g is 0, 1, 2 or 3 and;
the subscript n is independently 0, 1 or 2;
with the proviso that the compound is not methyl 3-(4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)propanoate, 3-(4-((3-(2-chloro-6-methylphenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)propanoic acid, 3-(4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)propanoic acid, ethyl 3-(4-((4-(3-chlorophenyl)-2-(trifluoromethyl)furan-3-yl)methoxy)-2-methylphenyl)propanoate and 3-(3-fluoro-5-methyl-4-((3-methyl-5-phenylisoxazol-4-yl)methoxy)phenyl)propanoic acid.
11 . The compound of claim 10 , wherein: X is —CH 2 —; Y is —O—; Z is —(CR 4 R 5 ) n ; and V is a bond.
12 . The compound of claim 11 , wherein Q is selected from the group consisting of
wherein A 1 , A 2 , A 3 and A 4 are independently selected from the group consisting of C and N, with the proviso that only 0, 1 or 2 of A 1 , A 2 , A 3 and A 4 is N and R 1 and subscript b are as previously defined.
13 . The compound of claim 10 of Formula (D)
or a pharmaceutically acceptable salt thereof, wherein:
A 1 , A 2 , A 3 and A 4 are independently selected from the group consisting of C and N, with the proviso that only 0, 1 or 2 of A 1 , A 2 , A 3 and A 4 is N;
J 1 , J 2 , J 3 , J 4 and J 5 are independently selected from the group consisting of N and C, with the proviso that only 0, 1 or 2 of J 1 , J 2 , J 3 , J 4 and J 5 is N;
each R 3 is independently selected from the group consisting of halo, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-7 cycloalkyl, substituted C 3-7 cycloalkyl, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 2-6 alkynyl, substituted C 2-6 alkynyl, cyano, —OR a , —NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR a C(O)R b , —SR a , —S(O)R a and —S(O) 2 R a ;
the subscript c is 0, 1, 2 or 3; and
E 1 , E 2 , E 3 , R 1 , R 2 , Z, V, R a , R b , subscript b and subscript g are as previously defined.
14 . The compound of claim 13 , wherein Z and V taken together are selected from the group consisting of
15 . The compound of claim 14 , wherein E 1 is C and one of E 2 and E 3 is N and the other of E 2 and E 3 is O or N.
16 . The compound of claim 15 , wherein A 1 , A 2 , A 3 and A 4 are all C, and J 1 , J 2 , J 3 , J 4 and J 5 are all C.
17 . The compound of claim 16 , wherein the subscript g is 0 or 1; the subscript c is 0 or 1 and the subscript b is 0, 1 or 2.
18 . The compound of claim 17 , wherein R 1 is halo, C 1-3 alkyl or CF 3 ; g is 0 or g is 1 and R 2 is CH 3 ; and R 3 is C 1-4 alkyl or halo.
19 . A compound or a pharmaceutically acceptable salt thereof of claim 1 or 10 selected from
3-(3,5-difluoro-4-((3-isopropyl-1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (55);
ethyl 3-(3,5-difluoro-4-((4-phenyl-1,2,3-thiadiazol-5-yl)methoxy)phenyl)propanoate (57);
3-(3,5-difluoro-4-((1-phenyl-1H-imidazol-5-yl)methoxy)phenyl)propanoic acid (59);
2-(2-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluoro-phenyl)cyclopropyl)acetic acid (62);
3-(3,5-difluoro-4-((1-phenyl-1H-1,2,3-triazol-5-yl)methoxy)phenyl)propanoic acid (65);
2-(2-(3,5-difluoro-4-((5-methyl-3-phenylisoxazol-4-yl)methoxy)phenyl)cyclopropyl)-acetic acid (67);
3-(3,5-difluoro-4-((1-isobutyl-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (68);
2-(2-(3,5-difluoro-4-((1-isobutyl-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-cyclopropyl)acetic acid (69);
2-(3,5-Difluoro-4-((1-isobutyl-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-cyclopropanecarboxylic acid (70);
3-(3,5-difluoro-4-((5-phenyloxazol-4-yl)methoxy)phenyl)propanoic acid (71);
3-(4-((1-benzyl-1H-imidazol-2-yl)methoxy)-3,5-difluorophenyl)propanoic acid (72);
3-(3,5-difluoro-4-((5-methyl-2-phenylfuran-3-yl)methoxy)phenyl)propanoic acid (73);
3-(3,5-difluoro-4-((1-methyl-5-phenyl-1H-pyrazol-4-yl)methoxy)phenyl)propanoic acid (74);
3-(3,5-difluoro-4-((5-methyl-3-phenylisoxazol-4-yl)methoxy)phenyl)propanoic acid (75);
3-(3,5-difluoro-4-((3-methyl-5-phenylisoxazol-4-yl)methoxy)phenyl)propanoic acid (76);
2-(3,5-difluoro-4-((5-methyl-3-phenylisoxazol-4-yl)methoxy)phenyl)cyclopropanecarboxylic acid (77);
2-(3,5-difluoro-4-((3-(4-fluorophenyl)-5-methylisoxazol-4-yl)methoxy)phenyl)cyclopropanecarboxylic acid (78);
3-(3,5-difluoro-4-((3-(4-fluorophenyl)-5-methylisoxazol-4-yl)methoxy)phenyl)propanoic acid (79);
3-(4-((3′,5-dimethyl-3,5′-biisoxazol-4′-yl)methoxy)-3,5-difluorophenyl)propanoic acid (80);
3-(4-((3-(1H-pyrrol-1-yl)thiophen-2-yl)methoxy)-3,5-difluorophenyl)propanoic acid (81);
3-(3,5-difluoro-4-((3-(4-methoxyphenyl)-5-methylisoxazol-4-yl)methoxy)phenyl)propanoic acid (82);
3-(4-((3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl)methoxy)-3,5-difluorophenyl)propanoic acid (83);
3-(4-((3,5-dimethylisoxazol-4-yl)methoxy)-3,5-difluorophenyl)propanoic acid (84);
3-(4-((3-(4-chlorophenyl)-5-methylisoxazol-4-yl)methoxy)-3,5-difluorophenyl)propanoic acid (85);
3-(3,5-difluoro-4-((1-isopropyl-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (86);
3-(3,5-difluoro-4-(2-(5-methyl-3-phenylisoxazol-4-yl)-2-oxoethoxy)phenyl)propanoic acid (87);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)butanoic acid (88);
3-(3,5-difluoro-4-((5-phenylthiazol-4-yl)methoxy)phenyl)propanoic acid (89);
2-(4-((4-phenyl-1,2,3-thiadiazol-5-yl)methoxy)phenylthio)acetic acid (90);
3-(3,5-difluoro-4-((2-methyl-4-phenylthiazol-5-yl)methoxy)phenyl)propanoic acid (91);
3-(3,5-difluoro-4-((4-(4-fluorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)phenyl)propanoic acid (92);
3-(4-((4-(3-chlorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (93);
2-(3,5-difluoro-4-((2-methyl-4-phenylthiazol-5-yl)methoxy)phenyl)cyclopropane carboxylic acid (94);
2-(3,5-difluoro-4-((5-methyl-3-phenylisoxazol-4-yl)methoxy)benzyloxy)acetic acid (95);
2-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorobenzyloxy)acetic acid (96);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (97);
3-(3,5-difluoro-4-((5-methyl-3-phenylisoxazol-4-yl)methoxy)phenyl)-2-methylpropanoic acid (98);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2,2-dimethylpropanoic acid (99);
2-(6-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid (100);
2-(6-((5-methyl-3-phenylisoxazol-4-yl)methoxy)-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid (101);
3-(4-((1-tert-butyl-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (102);
3-(3,5-difluoro-4-((2-methyl-4-phenylthiazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (103);
(R)-3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (104);
(S)-3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (105);
4-(4-((3-methyl-1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)butanoic acid (106);
3-(3,5-difluoro-4-((3-methyl-1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (107);
3-(3,5-difluoro-4-((1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl) propanoic acid (108);
3-(3,5-difluoro-4-((1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (109);
3-(3,5-difluoro-4-((1-(4-methoxyphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (110);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (111);
3-(3,5-difluoro-4-((1-(4-fluorophenyl)-4-methyl-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (112);
3-(4-((4-(4-chlorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)-3,5-difluorophenyl)-2,2-difluoropropanoic acid (113);
3-(4-((1-(3,4-difluorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (114);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-fluoropropanoic acid (115);
2-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorobenzyl)cyclopropanecarboxylic acid (116);
3-(4-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (117);
3-(4-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2,2-difluoropropanoic acid (118);
2-(5-((5-methyl-3-phenylisoxazol-4-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid (119);
2-(5-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid (120);
2-(5-((5-methyl-3-phenylisoxazol-4-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)propanoic acid (121);
2-(5-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)propanoic acid (122);
3-(4-((4-(4-chlorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (123);
2-(3,5-difluoro-4-((4-phenyl-1,2,3-thiadiazol-5-yl)methoxy)phenyl)cyclopropane carboxylic acid (124);
2-(3,5-difluoro-4-((3-methyl-1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)cyclopropane carboxylic acid (125);
3-(3,5-difluoro-4-((1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)phenyl)propanoic acid (126);
4-(4-((4-(4-chlorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)phenyl)-4-oxobutanoic acid (128);
(E)-4-(4-((4-(4-chlorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)phenyl)-3-methylbut-2-enoic acid (130);
(E)-5-(4-((4-(4-chlorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)phenyl)-3-methylpent-2-enoic acid (131);
5-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-3-methyl pentanoic acid (132);
4-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-3-methylbutanoic acid (133);
3-(4-((4-(3,4-difluorophenyl)-1,2,3-thiadiazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (134);
3-(4-((1-(3,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)propanoic acid (135);
3-(4-((4-isopropoxy-2-methylthiazol-5-yl)methoxy)phenyl)propanoic acid (136);
3-(3,5-difluoro-4-((1-(4-isopropylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (137);
3-(3,5-difluoro-4-((3-methyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (138);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-(trifluoromethyl)phenyl)-2-methylpropanoic acid (139);
3-(4-((1-(4-carbamoylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (140);
3-(4-((1-(4-cyanophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (141);
3-(4-((1-(2,3-dihydro-1H-inden-5-yl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (142);
3-(4-((1-(4-butylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (143);
3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (144);
3-(3,5-difluoro-4-((3-methyl-1-p-tolyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (145);
3-(3,5-difluoro-4-((1-(3-isopropylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (146);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (147);
3-(4-((1-(3,4-dimethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (148);
3-(4-((1-(3-chloro-4-methylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (149);
3-(4-((1-(3-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (150);
3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-fluorophenyl)-2-methylpropanoic acid (151);
3-(3,5-difluoro-4-((1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (152);
3-(4-((1-(3,5-dimethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (153);
3-(4-((1-(4-chlorophenyl)-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (154);
3-(4-((1-(4-chloro-3-methylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (155);
3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-methylphenyl)-2-methylpropanoic acid (156);
3-(4-((1-(4-ethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (157);
3-(4-((1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (158);
(R)-3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (159);
(S)-3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (160);
3-(4-((1-(4-ethylphenyl)-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (161);
3-(4-((1-(4-chlorophenyl)-3-ethyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (162);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-ethoxypropanoic acid (163);
3-(4-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2-methoxyphenyl)-2-methylpropanoic acid (164);
3-(4-((1-(4-Cyclohexylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (165);
3-(3,5-Difluoro-4-((3-methyl-1-(4-propylphenyl)-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (166);
2-(5-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-6-fluoro-2,3-dihydro-1H-inden-1-yl)acetic acid (167);
2-(4-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)cyclopent-1-enecarboxylic acid (168);
3-(4-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-fluorophenyl)-2-methylpropanoic acid (169);
3-(4-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-methylphenyl)-2-methylpropanoic acid (170);
3-(4-((1-(5-Chloropyrimidin-2-yl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (171);
3-(4-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)benzylidene)cyclobutanecarboxylic acid (172);
3-(4-((1-(4-Chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-methoxyphenyl)-2-methylpropanoic acid (173);
3-(3,5-Dichloro-4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (174);
3-(3,5-Difluoro-4-((1-methyl-5-phenoxy-3-(trifluoromethyl)-1H-pyrazol-4-yl)methoxy)phenyl)-2-methylpropanoic acid (175);
3-(4-((5-(4-Chlorophenoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic Acid (176);
3-(3,5-Difluoro-4-((5-methyl-2-phenylfuran-3-yl)methoxy)phenyl)-2-methylpropanoic acid (177);
3-(4-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)-2-methylpropanoic acid (178);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2-ethylphenyl)propanoic acid (179);
2-(5-((1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid (180);
2-(5-((1-(2,3-dihydro-1H-inden-5-yl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid (181);
2-(5-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid (182);
3-(3,5-difluoro-4-((3-methyl-1-phenyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (183);
2-(6-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-1,2,3,4-tetrahydronaphthalen-1-yl)acetic acid (184);
3-(3,5-difluoro-4((3-methyl-1-(pyridin-2-yl)-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylpropanoic acid (185);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-3-methylbutanoic acid (186);
3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-3-methylbutanoic acid (187);
4-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)butanoic acid (188);
4-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)butanoic acid (189);
4-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)butanoic acid (190);
4-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3,5-difluorophenyl)butanoic acid (191);
4-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylbutanoic acid (192);
4-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)phenyl)-2-methylbutanoic acid (193);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-methoxyphenyl)propanoic acid (194);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-3-fluoro-2-methylphenyl)propanoic acid (195);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2-ethyl-3-fluorophenyl)propanoic acid (196);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dimethylphenyl)propanoic acid (197);
3-(4-((1-(4-chlorophenyl)-1H-pyrazol-5-yl)methoxy)-3-fluoro-2-methylphenyl)propanoic acid (198);
3-(4-((1-(4-chlorophenyl)-1H-pyrazol-5-yl)methoxy)-2,3-dimethylphenyl)propanoic acid (199);
3-(4-((3-(4-chlorophenyl)-5-methylisoxazol-4-yl)methoxy)-2,3-dimethylphenyl)propanoic acid (200);
3-(4-((1-(4-ethylphenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dimethylphenyl)propanoic acid (201);
3-(4-((1-(4-ethylphenyl)-1H-pyrazol-5-yl)methoxy)-2,3-dimethylphenyl)propanoic acid (202);
3-(4-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-5,6,7,8-tetrahydro naphthalen-1-yl)propanoic acid (203); and
3-(7-((1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)propanoic acid (207).
20 . A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
21 . A method of treating a disease or condition selected from the group consisting of Type I diabetes, Type II diabetes and metabolic syndrome, said method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 .
22 . The method of claim 21 , wherein said disease is Type II diabetes.
23 . A method of stimulating insulin production, said method comprising administering an effective amount of a compound of claim 1 to a mammal in need of such treatment.
24 . The method of claim 23 , wherein said mammal is a human.
25 . A method of lowering blood glucose in a mammal, said method comprising administering an effective amount of a compound of claim 1 to a mammal in need of such treatment.
26 . The method of claim 25 , wherein said mammal is a human.
27 . A method of modulating GPR120 activity in a cell, said method comprising contacting said cell with an effective amount of a compound of claim 1 .