US2009082392A1PendingUtilityA1
Substituted Carboxylic Acids
Assignee: INST FOR PHARM DISCOVERY INCPriority: Apr 30, 2003Filed: Apr 15, 2008Published: Mar 26, 2009
Est. expiryApr 30, 2023(expired)· nominal 20-yr term from priority
A61P 3/10A61P 35/00A61P 43/00A61P 25/00C07D 307/80C07D 471/04C07D 277/66C07C 69/736C07D 307/92C07D 263/57C07D 405/10C07D 209/08C07D 307/91C07D 417/04
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Claims
Abstract
The present invention relates to compounds and pharmaceutically acceptable salts of formula (I): which are useful in the treatment of metabolic disorders related to insulin resistance or hyperglycemia. These compounds include inhibitors of protein tyrosine phosphatase (PTP-1B) that are useful in the treatment of diabetes and other PTP-1B mediated diseases, such as cancer, neurodegenerative diseases and the like. The compounds of the invention are also useful in pharmaceutical compositions and methods of treating the aforementioned conditions.
Claims
exact text as granted — not AI-modified1 . A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein
n is 0, 1, 2, 3, or 4;
R 1 is H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, or C 3 -C 6 alkenyl;
R 2 is phenyl, phenyl(C 1 -C 4 ) alkyl, C 1 -C 6 alkyl, —(C 1 -C 4 ) alkyl-C(O)NH 2 , —(C 1 -C 4 ) alkyl-C(O)NH(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-C(O)N(C 1 -C 4 ) alkyl(C 1 -C 4 ) alkyl, —(C 1 -C 4 ) alkyl-S(O) b —(C 1 -C 4 ) alkyl, (C 1 -C 4 ) hydroxyalkyl, —(C 1 -C 4 ) alkyl-heterocycloalkyl, wherein the heterocycloalkyl group is optionally fused to a phenyl ring and wherein the heterocycloalkyl portion, the phenyl portion, or both are optionally substituted with a total of 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —SO 2 —(C 1 -C 4 ) alkyl, haloalkyl, or haloalkoxy;
wherein b is 0, 1, or 2;
R 20 , R 21 , R 22 , and R 23 are independently H, arylalkoxy, arylalkyl, halogen, alkyl, haloalkyl, OH, alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl), NH-aryl, NHC(O)—(C 1 -C 4 alkyl)-aryl, N(C 1 -C 4 alkyl)C(O)—(C 1 -C 4 )alkyl-aryl, N(C 1 -C 4 )alkyl-aryl, —NHSO 2 -aryl, or —N(C 1 -C 4 alkyl)SO 2 aryl, wherein each of the above aryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, haloalkoxy;
L is —SO 2 NH—, —SO 2 N(C 1 -C 4 ) alkyl-, —NHSO 2 —, —N(C 1 -C 4 alkyl)SO 2 —, O, —C(O)NH—, —C(O)N(C 1 -C 4 )alkyl-, —SO 2 —, —C(O)—(C 1 -C 4 ) alkyl-, —(C 1 -C 4 ) alkyl-C(O)—, —NH—, —(C 1 -C 6 alkyl)-O—N═, or —N(C 3 -C 4 alkyl)-, wherein the alkyl group is optionally substituted with phenyl, wherein the phenyl is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
L 3 is a bond, absent, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, —C(O)—, —C(O)NH—, or —NHC(O)—;
the A-ring is aryl selected from the group consisting of phenyl, naphthyl and fluorenyl, or heteroaryl, each of which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 ) alkyl (C 1 -C 6 ) alkyl;
Q is H, aryl, heteroaryl, -heteroaryl-alkyl, -aryl-heteroaryl, aryl-C(O)-aryl, aryl-(C 1 -C 4 alkyl)-aryl, heteroaryl-(C 1 -C 4 alkyl)-aryl, -heteroaryl-aryl, wherein the aryl group is a phenyl, naphthyl, or fluorenyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, alkanoyl, arylalkanoyl, alkoxycarbonyl, arylalkoxycarbonyl, heteroarylcarbonyl, heteroaryl, heterocycloalkylcarbonyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 )alkyl, —C(O)N(C 1 -C 6 ) alkyl(C 1 -C 6 )alkyl, or —SO 2 -aryl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, haloalkyl or haloalkoxy.
2 . A compound according to claim 1 , wherein
R 2 is phenyl, phenyl(C 1 -C 4 ) alkyl, C 1 -C 6 alkyl, —(C 1 -C 4 ) alkyl-C(O)NH 2 , —(C 1 -C 4 ) alkyl-C(O)NH(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-C(O)N(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-S(O) b —(C 1 -C 4 ) alkyl, (C 1 -C 4 ) hydroxyalkyl, —(C 1 -C 4 ) alkyl-phthalimidyl, —(C 1 -C 4 ) alkyl-piperidinyl, —(C 1 -C 4 ) alkyl-pyrrolidinyl, —(C 1 -C 4 ) alkyl-morpholinyl, wherein the phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups are optionally fused to a phenyl ring and wherein said phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups are, the phenyl portion, or both are optionally substituted with a total of 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —SO 2 —(C 1 -C 4 ) alkyl (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )haloalkoxy;
wherein b is 0, 1, or 2;
and
Q is H, pyrido[1,2-a]indolyl, indolyl, isoindolyl, indolizinyl, imidazo[1,2-a]pyridine, -phenyl-C(O)-phenyl, -phenyl-(C 1 -C 4 ) alkyl-phenyl, -pyridyl-phenyl, fluorenyl, -fluorenyl-pyridyl, -fluorenyl-phenyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, -benzimidazolyl-(C 1 -C 4 ) alkyl-phenyl, benzoxazolyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, -indolyl-(C 1 -C 4 ) alkyl-phenyl, -phenyl-benzoxazolyl, benzo[b]thienyl, dibenzo[b,d]furan, phenyl, or dibenzothienyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, phenyl(C 1 -C 4 ) alkoxycarbonyl, pyridylcarbonyl, pyridyl, piperidinyl, pyrrolidinylcarbonyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 )alkyl, —C(O)N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
3 . A compound according to claim 2 , wherein
the A-ring is selected from phenyl, naphthyl, pyridyl, thiazolyl, benzofuranyl, dibenzofuranyl, pyrrolyl, furanyl, isoindolyl, or indolyl each of which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 ) alkyl; and R 20 , R 21 , R 22 , and R 23 are independently H, phenylalkoxy, phenylalkyl, halogen, alkyl, CF 3 , OH, alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, NH-phenyl, NHC(O)—(C 1 -C 4 ) alkyl-phenyl, N(C 1 -C 4 alkyl)C(O)—(C 1 -C 4 ) alkyl-phenyl, N(C 1 -C 4 )alkyl-phenyl, —NHSO 2 -phenyl, or —N(C 1 -C 4 alkyl)SO 2 -phenyl, wherein the phenyl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 2 haloalkyl, or C 1 -C 2 haloalkoxy.
4 . A compound according to claim 3 , wherein
L is —SO 2 NH—, —SO 2 N(C 1 -C 4 ) alkyl-, —NHSO 2 , O, —C(O)NH—, —C(O)N(C 1 -C 4 )alkyl-, —SO 2 —, —C(O)—(C 1 -C 4 ) alkyl-, —(C 1 -C 4 ) alkyl-C(O)—, —NH—, —N(C 1 -C 4 ) alkyl-, wherein the alkyl group is optionally substituted with phenyl, which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
5 . A compound according to claim 4 , of the formula
wherein
R 1 is H or C 1 -C 6 alkyl;
R 2 is phenyl, phenyl(C 1 -C 4 ) alkyl, C 1 -C 6 alkyl, —(C 1 -C 4 ) alkyl-C(O)NH 2 , —(C 1 -C 4 ) alkyl-S(O) b —(C 1 -C 4 ) alkyl, or (C 1 -C 4 ) hydroxyalkyl, wherein the phenyl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —SO 2 —(C 1 -C 4 ) alkyl, (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )haloalkoxy;
v is 0, 1, 2, 3, or 4;
R 10 at each occurrence is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl; and
L 3 is a bond, absent, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, or —C(O)—.
6 . A compound according to claim 5 , wherein
Q is H, pyrido[1,2-a]indolyl, indolyl, imidazo[1,2-a]pyridine, -phenyl-C(O)-phenyl, -phenyl-(C 1 -C 4 ) alkyl-phenyl, fluorenyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, -indolyl-(C 1 -C 4 ) alkyl-phenyl, -phenyl-benzoxazolyl, benzo[b]thienyl, dibenzo[b,d]furan, phenyl, or dibenzothienyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 ) alkanoyl, alkoxycarbonyl, phenyl(C 1 -C 4 ) alkoxycarbonyl, pyridylcarbonyl, pyridyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
7 . A compound according to claim 6 , wherein
R 2 is phenyl, phenyl(C 1 -C 4 ) alkyl, or (C 1 -C 6 )alkyl, wherein the phenyl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or —SO 2 —(C 1 -C 4 ) alkyl, CF 3 or OCF 3 ; and R 20 , R 21 , R 22 , and R 23 are independently selected from H, halogen, alkyl, OH, alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl).
8 . A compound according to claim 7 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, or —C(O)—; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, benzo[b]thienyl, dibenzo[b,d]furan, phenyl, or dibenzothienyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyridyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
9 . A compound according to claim 8 of the formula:
10 . A compound according to claim 9 , wherein
L is —SO 2 NH—, —SO 2 N(C 1 -C 4 alkyl)-, or —SO 2 — wherein the alkyl group is optionally substituted with phenyl, which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
11 . A compound according to claim 10 , wherein
R 1 is H; R 21 is H, NO 2 , C 1 -C 6 alkyl, or halogen; and R 2 is phenyl, benzyl, or (C 1 -C 6 )alkyl, wherein each phenyl group is optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or —SO 2 —(C 1 -C 4 ) alkyl, CF 3 or OCF 3 .
12 . A compound according to claim 11 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 ) alkyl-; Q is -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, dibenzo[b,d]furan, or dibenzothienyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyridyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
13 . A compound according to claim 9 , wherein
L is —O—.
14 . A compound according to claim 13 , wherein
R 1 is H; R 21 is H, NO 2 , C 1 -C 6 alkyl, or halogen; and R 2 is phenyl, phenyl(C 1 -C 4 )alkyl, or (C 1 -C 6 )alkyl, wherein each phenyl group is optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or —SO 2 —(C 1 -C 4 ) alkyl, CF 3 or OCF 3 .
15 . A compound according to claim 14 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 ) alkyl-; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, or -indolyl-(C 1 -C 4 ) alkyl-phenyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
16 . A compound according to claim 9 , wherein
L is —C(O)NH—, —C(O)N(C 1 -C 4 )alkyl-, —C(O)—(C 1 -C 4 ) alkyl-, —NH—, or —N(C 1 -C 4 ) alkyl-, wherein the alkyl groups are optionally substituted with phenyl, which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 2 haloalkyl, or C 1 -C 2 haloalkoxy.
17 . A compound according to claim 14 , wherein
L is —C(O)NH—, or —C(O)N(C 1 -C 4 )alkyl-; R 1 is H; R 21 is H, NO 2 , C 1 -C 6 alkyl, or halogen.
18 . A compound according to claim 17 R 2 is phenyl, phenyl(C 3 -C 4 )alkyl, or (C 1 -C 6 )alkyl, wherein each phenyl group is optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or —SO 2 —(C 1 -C 4 ) alkyl, CF 3 or OCF 3 .
19 . A compound according to claim 18 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 ) alkyl-; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C 3 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, or -indolyl-(C 1 -C 4 )alkyl-phenyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
20 . A compound according to claim 5 , wherein
L is —NH—, or —N(C 1 -C 4 ) alkyl-.
21 . A compound according to claim 20 , wherein
R 1 is H; R 21 is H, NO 2 , C 1 -C 6 alkyl, or halogen; and R 2 is phenyl, phenyl(C 1 -C 4 ) alkyl, C 1 -C 6 alkyl, —(C 1 -C 4 ) alkyl-C(O)NH 2 , —(C 1 -C 4 ) alkyl-S(O) b —(C 1 -C 4 ) alkyl, or (C 1 -C 4 ) hydroxyalkyl, wherein the phenyl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —SO 2 —(C 1 -C 4 ) alkyl, CF 3 or OCF 3 .
22 . A compound according to claim 21 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 ) alkyl-; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, or -indolyl-(C 1 -C 4 )alkyl-phenyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
23 . A compound according to claim 2 , of the formula:
wherein
v is 0, 1, 2, 3, or 4;
R 10 at each occurrence is independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl; and
L is —C(O)—(C 1 -C 4 ) alkyl-, —(C 1 -C 4 ) alkyl-C(O)—, wherein the alkyl groups are optionally substituted with phenyl, which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
24 . A compound according to claim 23 , wherein
R 1 is H; R 20 , R 22 , and R 23 are independently selected from H, halogen, alkyl, OH, alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl); R 21 is H, NO 2 , C 1 -C 6 alkyl, or halogen; and R 2 is phenyl, phenyl(C 1 -C 4 ) alkyl, C 1 -C 6 alkyl, —(C 1 -C 4 ) alkyl-phthalimidyl, —(C 1 -C 4 ) alkyl-piperidinyl, —(C 1 -C 4 ) alkyl-pyrrolidinyl, —(C 1 -C 4 ) alkyl-morpholinyl, wherein the phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups are optionally fused to a phenyl ring and wherein said phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups are, the phenyl portion, or both are optionally substituted with a total of 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —SO 2 —(C 1 -C 4 ) alkyl (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )haloalkoxy; wherein b is 0, 1, or 2.
25 . A compound according to claim 21 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 ) alkyl-; Q is indolyl, -phenyl-C(O)-phenyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, dibenzo[b,d]furan, or dibenzothienyl, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, alkanoyl, phenyl(C 1 -C 4 )alkanoyl, alkoxycarbonyl, pyridylcarbonyl, pyrrolidinylcarbonyl, or —SO 2 -phenyl, wherein the cyclic groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, NO 2 , OH, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 or OCF 3 .
26 . A compound according to claim 25 , wherein
R 2 is —(C 1 -C 4 ) alkyl-phthalimidyl, —(C 1 -C 4 ) alkyl-piperidinyl, —(C 1 -C 4 ) alkyl-pyrrolidinyl, —(C 1 -C 4 ) alkyl-morpholinyl, wherein the phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups are optionally fused to a phenyl ring and wherein said phthalimidyl, piperidinyl, pyrrolidinyl, or morpholinyl groups are, the phenyl portion, or both are optionally substituted with a total of 1, 2, 3, or 4 groups that are independently halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —SO 2 —(C 1 -C 4 ) alkyl (C 1 -C 4 )haloalkyl, or (C 1 -C 4 )haloalkoxy.
27 . A compound according to claim 26 , wherein
L 3 is a bond, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 ) alkyl-; Q is indolyl, -benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, indolizinyl, benzofuranyl, -indolyl-(C 1 -C 4 ) alkyl-phenyl, or dibenzo[b,d]furan, each of which is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 6 alkoxy, halogen, CF 3 or OCF 3 .
28 . A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable solvent, carrier, excipient or adjuvant.
29 . A method of treating diabetes in a patient needing such treatment comprising administering a compound of claim 1 or a pharmaceutical composition of claim 28 .
30 . A compound according to claim 1 selected from the group consisting of
({4′-[3-(benzylamino)imidazo[1,2-a]pyridin-2-yl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
{[4′-(5-methyl-1H-indol-1-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
({4′-[3-(butylamino)imidazo[1,2-a]pyridin-2-yl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
methyl ({4′-[(2-benzoylphenoxy)methyl]biphenyl-4-yl}oxy)(phenyl)acetate;
methyl ({4′-[(2-benzylphenoxy)methyl]biphenyl-4-yl}oxy)(phenyl)acetate;
methyl ({4′-[(9H-fluoren-2-yloxy)methyl]biphenyl-4-yl}oxy)(phenyl)acetate;
methyl ({4′-[(3-benzoylphenoxy)methyl]biphenyl-4-yl}oxy)(phenyl)acetate;
({4′-[(3-benzoylphenoxy)methyl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
({4′-[(2-benzoylphenoxy)methyl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
2-([4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]oxy)-3-phenylpropanoic acid;
{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
[4-(1-benzyl-1H-indol-6-yl)phenoxy](phenyl)acetic acid;
({4′-[10-(ethoxycarbonyl)pyrido[1,2-a]indol-3-yl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
{[4′-(1-benzofuran-2-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
{[4′-(1H-indol-1-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
methyl {[4′-(1-benzyl-1H-indol-6-yl)biphenyl-4-yl]oxy}(phenyl)acetate;
4-(4′-Dibenzofuran-4-yl-biphenyl-4-yl)-4-oxo-2-(3-trifluoromethyl-benzyl)-butyric acid
{[4′-(1-benzyl-1H-indol-6-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
{[4′-(1-benzyl-1H-indol-5-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
2-{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]oxy}propanoic acid;
N-{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]sulfonyl}phenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}phenylalanine;
N-benzyl-N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}glycine;
({[4-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}amino)(phenyl)acetic acid;
(2R)-2-{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]oxy}-3-phenylpropanoic acid;
(2S)-2-{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]oxy}-4-phenylbutanoic acid;
({4′-[(2-butyl-1-benzofuran-3-yl)methyl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
ethyl N-{([4-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-N-methylphenylalaninate;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-N-methylphenylalanine;
ethyl N-{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]carbonyl}phenylalaninate;
N-{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]carbonyl}phenylalanine;
{([2′-(1,3-benzoxazol-2-yl)-1,1′:4′,1″-terphenyl-4-yl]oxy}(phenyl)acetic acid;
({4′-[(2-butyl-1-benzofuran-3-yl)carbonyl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
methyl {[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]sulfonyl}(phenyl)acetate;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]carbonyl}phenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]carbonyl}-N-methylphenylalanine;
{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]sulfonyl}(phenyl)acetic acid;
({[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]carbonyl}amino)(phenyl)acetic acid;
2-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]oxy}propanoic acid;
{[4′-(1-butylindolizin-2-yl)biphenyl-4-yl]amino}(phenyl)acetic acid;
N-({4′-[(2-butyl-1-benzofuran-3-yl)methyl]biphenyl-4-yl}sulfonyl)-N-methylphenylalanine;
N-({4′-[(2-butyl-1-benzofuran-3-yl)methyl]biphenyl-4-yl}carbonyl)-N-methylphenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]carbonyl}-N-methylvaline;
2-benzyl-4-[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]-4-oxobutanoic acid;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]phenylalanine;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]-N-methyl-L-phenylalanine;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]-N-methyl-D-phenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)-3-fluorobiphenyl-4-yl]sulfonyl}phenylalanine;
{[4′-(1-benzothien-2-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]-N-(4-nitrobenzoyl)-L-phenylalanine;
[(4′-dibenzo[b,d]furan-4-ylbiphenyl-4-yl)oxy](phenyl)acetic acid;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)-3-fluorobiphenyl-4-yl]sulfonyl}-N-methylphenylalanine;
[(4″-butyl-1,1′:4′,1″-terphenyl-4-yl)oxy](phenyl)acetic acid;
N 2 -[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]glutamine;
4-[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-4-oxobutanoic acid;
({4′-[(2-benzyl-7-fluoro-1-benzofuran-3-yl)carbonyl]biphenyl-4-yl}oxy)(phenyl)acetic acid;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]methionine;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]serine;
N-[4′-(2-benzyl-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]alanine;
N-{4′-[(2-benzyl-7-ethoxy-1-benzofuran-4-yl)methyl]-3-nitrobiphenyl-4-yl}phenylalanine;
N-[4′-(2-benzyl-4-fluoro-1-benzofuran-3-yl)-3-nitrobiphenyl-4-yl]phenylalanine;
2-benzyl-4-[4′-(2-benzyl-1-benzofuran-3-yl)-3,5-dimethylbiphenyl-4-yl]-4-oxobutanoic acid;
2-benzyl-4-[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-3-yl]-4-oxobutanoic acid;
2-benzyl-4-[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-2-yl]-4-oxobutanoic acid;
N-{4′-(2-benzyl-1-benzofuran-3-yl)-3-[(phenylacetyl)amino]biphenyl-4-yl}phenylalanine;
4-[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]-2-[4-(methylsulfonyl)benzyl]-4-oxobutanoic acid;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-4-fluorophenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-4-fluoro-N-methylphenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-3-fluorophenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-3-fluoro-N-methylphenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-N-ethyl-4-fluorophenylalanine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}leucine;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}alanine;
2-({[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}amino)butanoic acid;
4-(4-Dibenzofuran-4-yl-phenyl)-4-oxo-2-(3-trifluoromethyl-benzyl)-butyric acid;
N-{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}-N-[3-(trifluoromethyl)benzyl]leucine;
2-{{[4′-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}[3-(trifluoromethyl)benzyl]amino}butanoic acid;
methyl 4-(4′-dibenzo[b,d]furan-4-ylbiphenyl-4-yl)-4-oxo-2-[3-(trifluoromethyl)benzyl]butanoate;
[(4′-{[(9-oxo-9H-fluoren-1-yl)oxy]methyl}biphenyl-4-yl)oxy](phenyl)acetic acid;
methyl {[4′-(1-benzofuran-2-yl)biphenyl-4-yl]oxy}(phenyl)acetate;
({4′-[3-(butylamino)imidazo[1,2-a]pyridin-2-yl]biphenyl-4-yl}amino)(phenyl)acetic acid;
{[4′-(1-benzothien-3-yl)biphenyl-4-yl]oxy}(phenyl)acetic acid;
methyl {[4′-(1-benzyl-1H-indol-5-yl)biphenyl-4-yl]oxy}(phenyl)acetate;
ethyl ({[4-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]sulfonyl}amino)(phenyl)acetate;
methyl 2-(4-benzo[b]naphtho[2,3-d]furan-11-ylphenoxy)propanoate;
3-({[4-(2-benzyl-1-benzofuran-3-yl)biphenyl-4-yl]carbonyl}amino)butanoic acid;
N-{[4-(5-methyl-1H-indol-1-yl)biphenyl-4-yl]carbonyl}phenylalanine;
N-{[4-(1H-indol-1-yl)biphenyl-4-yl]carbonyl}-L-phenylalanine;
N-(3-fluoro-3-nitro-1,1′:4′,1″-terphenyl-4-yl)phenylalanine;
2-benzyl-4-[4-(1H-indol-1-yl)biphenyl-4-yl]-4-oxobutanoic acid;
2-[4-(2-Benzyl-benzofuran-3-yl)-3-nitro-biphenyl-4-ylamino]-3-phenyl-propionic acid;
4-(4-dibenzo[b,d]furan-4-ylbiphenyl-4-yl)-4-oxo-2-[3-(trifluoromethyl)benzyl]butanoic acid;
[(4-dibenzo[b,d]thien-4-ylbiphenyl-4-yl)oxy](phenyl)acetic acid;
2-[4-(2-Benzyl-benzofuran-3-yl)-3-fluoro-biphenyl-4-sulfonylamino]-3-phenyl-propionic acid;
2-{[4-(2-Benzyl-benzofuran-3-yl)-3-fluoro-biphenyl-4-sulfonyl]-methyl-amino}-3-phenyl-propionic acid;
4-[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-yl]-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-4-oxo-butyric acid;
2-Benzyl-4-[4-(2-benzyl-benzofuran-3-yl)-3,5-dimethyl-biphenyl-4-yl]-4-oxo-butyric acid;
2-Benzyl-4-(4-indol-1-yl-biphenyl-4-yl)-4-oxo-butyric acid;
2-Benzyl-4-[4-(2-benzyl-benzofuran-3-yl)-biphenyl-3-yl]-4-oxo-butyric acid;
2-Benzyl-4-[4-(2-benzyl-benzofuran-3-yl)-biphenyl-2-yl]-4-oxo-butyric acid;
4-[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-yl]-2-(4-methanesulfonyl-benzyl)-4-oxo-butyric acid;
2-[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonylamino]-3-(4-fluoro-phenyl)-propionic acid;
2-{[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonyl]-methyl-amino}-3-(4-fluoro-phenyl)-propionic acid;
2-[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonylamino]-3-(3-fluoro-phenyl)-propionic acid;
2-{[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonyl]-methyl-amino}-3-(3-fluoro-phenyl)-propionic acid;
2-{[4-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonyl]-ethyl-amino}-3-(4-fluoro-phenyl)-propionic acid;
2-[4′-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonylamino]-4-methyl-pentanoic acid;
2-[4′-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonylamino]-propionic acid;
2-[4′-(2-Benzyl-benzofuran-3-yl)-biphenyl-4-sulfonylamino]-butyric acid;
2-(4′-Dibenzofuran-4-yl-biphenyl-4-sulfonylamino)-3-phenyl-propionic acid;
(4′-Dibenzofuran-4-yl-biphenyl-4-sulfonylamino)-phenyl-acetic acid;
2-{[4-(2-Dibenzofuran-4-yl-thiazol-4-yl)-benzenesulfonyl]-ethyl-amino}-3-phenyl-propionic acid;
(4′-Dibenzofuran-4-yl-biphenyl-4-ylmethoxyimino)-phenyl-acetic acid;
3-(4′-Dibenzofuran-4-yl-biphenyl-4-ylmethoxyimino)-3-phenyl-propionic acid;
[4′-(5-Chloro-indol-1-yl)-biphenyl-4-yloxy]-phenyl-acetic acid;
(3-Chloro-4′-dibenzofuran-4-yl-biphenyl-4-yloxy)-phenyl-acetic acid;
(4′-Dibenzofuran-4-yl-2-methyl-biphenyl-4-yloxy)-phenyl-acetic acid;
(4′-Dibenzofuran-4-yl-3-fluoro-biphenyl-4-yloxy)-phenyl-acetic acid;
(2-Chloro-4′-dibenzofuran-4-yl-biphenyl-4-yloxy)-phenyl-acetic acid; and
(4′-Dibenzofuran-4-yl-2-trifluoromethyl-biphenyl-4-yloxy)-phenyl-acetic acid.Join the waitlist — get patent alerts
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