Phenyl substituted carboxylic acids
View Patent ↗Disclosed are compounds and pharmaceutically acceptable salts of formula (A): which are useful in the treatment of metabolic disorders related to insulin resistance, leptin resistance, or hyperglycemia. Compounds of the invention include inhibitors of Protein tyrosine phosphatases, in particular Protein tyrosine phosphatase-1B (PTP-1B), that are useful in the treatment of diabetes and other PTP mediated diseases, such as cancer, neurodegenerative diseases and the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.
1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, or C 2 - C 6 alkenyl;
L 2 is a bond;
L 3 is a bond, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, -alkenyl-, or -phenyl-;
L 5 is —N(R 9 )C(O)—(C 1 -C 4 ) alkyl- or —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-, wherein
R 9 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, —SO 2 -aryl, heteroarylalkyl, or arylalkyl, wherein the aryl or heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, haloalkyl, or haloalkoxy;
R 20 , R 21 , R 22 , and R 23 are independently selected from H, arylalkoxy, arylalkyl, halogen, alkyl, alkoxy, NO 2 , NH 2 , CN, 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, and —N(C 1 -C 4 alkyl)SO 2 -aryl, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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;
Q is aryl, aryl-carbonyl-aryl, -aryl-O-aryl, -aryl-alkyl-aryl, -aryl-heteroaryl, -aryl-heterocycloalkyl, heteroaryl, or -heteroaryl-alkyl-aryl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, phenyl-C 1 -C 6 alkyl-, or phenyloxy-; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, aryl C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, aryl C 1 -C 6 alkoxycarbonyl, 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; and
Z is absent, H, —NHC(O)aryl, —N(C 1 -C 4 alkyl)C(O)aryl, or aryl, wherein the aryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, or NO 2 , or
Z is —NHC(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl, or —N(C 1 -C 4 )alkyl-C(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl.
2. A compound according to claim 1 , wherein
Q is phenyl, phenyl-O-phenyl, -phenyl-carbonyl-phenyl, phenyl-(C 1 -C 4 )alkyl-phenyl, phenyl-pyridyl, -phenyl-pyrimidyl, -phenyl-benzoturanyl, phenylindolyl, -phenyl-piperidinyl, -phenyl-pyrrolidinyl, -phenyl-piperazinyl, indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 )alkyl-phenyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, or imidazo[2,1-b]thiazol-3-one, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, or phenyl-(C 1 -C 6 )alkyl-; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, phenyl(C 2 -C 6 )alkanoyl, C 1 -C 6 alkoxycarbonyl, phenyl(C 1 -C 6 )alkoxycarbonyl, 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; and
Z is absent, H, or phenyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, or NO 2 .
3. A compound according to claim 2 , wherein
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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 selected from H, phenyl(C 1 -C 5 )alkoxy, phenyl(C 1 -C 6 )alkyl, halogen, (C 1 -C 6 )alkyl, 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, and —N(C 1 -C 4 alkyl)SO 2 -phenyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy.
4. A compound according to claim 3 , wherein
R 1 is H, C 1 -C 6 alkyl, benzyl, or allyl;
L 3 is a bond, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, -alkenyl-, or -phenyl-;
L 5 is —N(R 9 )C(O)—(C 1 -C 4 ) alkyl- or —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-, wherein
R 9 independently is H, C 1 -C 6 alkyl, —SO 2 -phenyl, —C 1 -C 6 alkyl-furanyl, —C 1 -C 6 - alkyl-tetrazolyl, —C 1 -C 6 - alkyl thienyl, —C 1 -C 6 - alkyl pyrrolyl, —C 1 -C 6 - alkyl pyridyl, or benzyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
5. A compound according to claim 1 , wherein
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 2 )alkyl;
Z is phenyl, optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, or NO 2 .
6. A compound according to claim 1 , wherein
R 22 and R 23 are both H;
L 5 is —N(R 9 )SO 2 —( C 1 -C 4 )alkyl-; and
Q is phenyl, -phenyl-O-phenyl, indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 ) alkyl-phenyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, or benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, or phenyl-(C 1 -C 6 )alkyl-.
7. A compound according to claim 1 , wherein
R 9 is H, C 1 -C 6 alkyl, —SO 2 -phenyl, —C 1 -C 6 alkyl-furanyl, —C 1 -C 6 alkyl-tetrazolyl, —C 1 -C 6 - alkyl thienyl, —C 1 -C 6 - alkyl pyrrolyl, —C 1 -C 6 - alkyl pyridyl, or benzyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, C 1 -C 2 haloalkyl, or C 1 -C 4 haloalkoxy; and
L 3 is a bond, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 )alkyl-, -alkenyl-, or -phenyl-.
8. A compound according to claim 1 , wherein
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl;
Q is phenyl, -phenyl-O-phenyl, benzofuranyl, indolyl, dibenzofuranyl, or benzofuranyl-CH 2 -phenyl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, CF 3 , OCF 3 , NR 6 R 7 , phenyl, or phenyl-(C 1 -C 6 )alkyl-; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, benzyl, C 2 -C 6 alkanoyl, phenyl(C 1 -C 6 )alkanoyl, C 1 -C 6 alkoxycarbonyl, 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 ; and
Z is phenyl, optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, CF 3 , OCF 3 , or NO 2 .
9. A compound according to claim 1 , wherein
L 3 is a bond, —( C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 )alkyl-;
L 5 is —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-;
R 1 is H or C 1 -C 6 alkyl;
R 21 is H; and
R 22 is H, phenyl(C 1 -C 6 )alkoxy, benzyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , CF 3 or OCF 3 .
10. A compound according to claim 1 , wherein
the A ring is phenyl, which is optionally substituted with 1, or 2 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF 3 , OCF 3 , NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl;
Q is phenyl, -phenyl-O-phenyl, benzofuranyl, dibenzofuranyl, or benzofuranyl-CH 2 -phenyl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, CF 3 , OCF 3 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl.
11. A compound according to claim 4 , of the formula:
wherein
n is 0, 1, 2, or 3;
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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;
R 1 is H, C 1 -C 6 alkyl, or benzyl; and
Q is phenyl, -phenyl-O-phenyl, -phenyl-(C 1 -C 4 )alkyl-phenyl, -phenyl -pyridyl, -phenyl-pyrimidyl, -phenyl-benzofuranyl, -phenyl-indolyl, -phenyl-piperidinyl, -phenyl-pyrrolidinyl, -phenyl-piperazinyl, indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 ) alkyl-phenyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, benzofuranyl-(C 1 -C 4 )alkyl-phenyl, or imidazo[2,1b]thiazol-3-one, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, or phenyl-(C 1 -C 6 )alkyl-.
12. A compound according to claim 11 , wherein
L 3 is a bond, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 )alkyl-; and
R 20 and R 21 are independently selected from H, phenyl(C 1 -C 6 )alkoxy, phenyl(C 1 -C 6 )alkyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, and N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 4 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , C 1 -C 2 haloalkyl, or C 1 -C 2 haloalkoxy.
13. A compound according to claim 12 , wherein
R 1 is H, or C 1 -C 6 alkyl, and
Q is phenyl, -phenyl-O-phenyl, indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 )alkyl-phenyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, benzofuranyl-(C 1 -C 4 )alkyl-phenyl, or imidazo[2,1-b]thiazol-3-one, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, or phenyl-(C 1 -C 6 )alkyl-.
14. A compound according to claim 13 of the formula:
wherein
n is 0, 1, 2, or 3;
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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.
15. A compound according to claim 12 , wherein
L 3 is a bond or —(C 1 -C 4 ) alkyl-.
16. A compound according to claim 1 , wherein
R 1 and R 21 are both H; and
R 22 is H, phenyl(C 1 -C 6 )alkoxy, benzyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 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 16 , wherein
R 9 is H, C 1 -C 6 alkyl, —SO 2 -phenyl, —C 1 -C 4 alkyl-furanyl, —C 1 -C 4 alkyl-tetrazolyl, —C 1 -C 4 - alkyl thienyl, —C 1 -C 4 - alkyl pyrrolyl, —C 1 -C 4 - alkyl pyridyl, or benzyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 , or OCF 3 .
18. A compound according to claim 17 , wherein
L 5 is —N(R 9 )C(O)—(C 1 -C 4 ) alkyl.
19. A compound according to claim 18 , wherein
R 9 is H, C 1 -C 6 alkyl, or benzyl, wherein phenyl group is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , 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 18 , wherein
R 9 is H, —SO 2 -phenyl, —C 1 -C 4 alkyl-furanyl, -C 1 -C 4 alkyl-tetrazolyl, —C 1 -C 4 - alkyl thienyl, -C 1 -C 4 - alkyl pyrrolyl, or —C 1 -C 4 - alkyl pyridyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 , or OCF 3 .
21. A compound according to claim 17 , wherein
L 5 is —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-.
22. A compound according to claim 21 , wherein R 9 is H, C 1 -C 6 alkyl, or benzyl, wherein phenyl group is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , 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 21 , wherein
R 9 is H, —SO 2 -phenyl, —C 1 -C 4 alkyl-furanyl, —C 1 -C 4 alkyl-tetrazolyl, —C 1 -C 4 - alkyl thienyl, —C 1 -C 4 - alkyl pyrrolyl, or —C 1 -C 4 - alkyl pyridyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, CF 3 , or OCF 3 .
24. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable solvent, carrier, adjuvant or excipient.
25. A compound according to claim 1 that is selected from the group consisting of
({benzyl [4′-(2benzyl-1-benzofuran-3-yl)biphenyl-4-yl]amino}sulfonyl)acetic acid;
3-({3-(benzyloxy)-4′-[(2-butyl--benzofuran-3-yl)methyl]biphenyl-4-yl}amino)-3-oxopropanoic acid;
({benzyl [4′-(1H-indol-1-yl)biphenyl-4-yl]amino}sulfonyl)acetic acid;
4-({3-(benzyloxy)-4′-[(2-butyl-1-benzofuran-3-yl)methyl]biphenyl-4-yl}amino)-4-oxobutanoic acid;
N-[3-Benzyloxy-4′-(2-butyl-benzofuran-3-ylmethyl)-biphenyl-4-yl]-malonamic acid.
26. A compound of the formula:
wherein
each R 30 independently represents hydroxy, amino, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF3, amino, or mono- or di(C 1 -C 6 )alkylamino;
L 3 is a bond, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, -alkenyl-, or -phenyl-;
L 5 is —N(R 9 )C(O)—(C 1 -C 4 ) alkyl-, or —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-;
R 1 is H, C 1 -C 6 alkyl, or benzyl;
R 20 and R 21 are independently selected from H, arylalkoxy, arylalkyl, halogen, alkyl, alkoxy, NO 2 , NH 2 , CN, 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, and —N(C 1 -C 4 alkyl)SO 2 -aryl, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
Q is phenyl, indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 )alkyl-phenyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, or benzofuranyl-(C 1 -C 4 )alkyl-phenyl, wherein the cyclic portion of each is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl
R 6 and R 7 are independently H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, phenyl(C 1 -C 6 )alkoxycarbonyl, or —SO 2 -aryl, wherein each phenyl is 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; and
L 2 is a bond;
where R 9 is H, C 1 -C 6 alkyl, —SO 2 -phenyl, —CH 2 -furanyl, —CH 2 -tetrazolyl, or benzyl, wherein the aromatic portion of each is optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 5 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )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, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, or —(C 1 -C 4 )alkyl-; and
R 20 and R 21 are independently selected from H, phenyl(C 1 -C 6 )alkoxy, phenyl(C 1 -C 6 )alkyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, and N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 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.
28. A compound according to claim 27 , wherein
R 1 is H, or C 1 -C 6 alkyl,
Q is phenyl, indolizinyl, benzofuranyl, indolyl, or dibenzofuranyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , or phenyl.
29. A compound according to claim 28 , wherein
L 3 is a bond or —C 1 -C 4 alkyl-.
30. A compound of formula:
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, or C 1 -C 6 alkenyl;
L 2 is a bond;
L 3 is —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, -alkenyl-, or -phenyl-;
L 5 is —N(R 9 )C(O)—(C 1 -C 4 ) alkyl-, or —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-, wherein
R 9 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, —SO 2 -aryl, heteroarylalkyl, or arylalkyl, wherein the aryl or heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, haloalkyl, or haloalkoxy;
R 20 , R 21 , R 22 , and R 23 are independently selected from H, arylalkoxy, arylalkyl, halogen, alkyl, alkoxy, NO 2 , NH 2 , CN, 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, and —N(C 1 -C 4 alkyl)SO 2 -aryl, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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;
Q is aryl, -aryl-carbonyl-aryl, -aryl-O-aryl, -aryl-alkyl-aryl, -aryl-heteroaryl, -aryl-heterocycloalkyl, -heteroaryl, or -heteroaryl-alkyl-aryl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, phenyl-C 1 -C 6 alkyl-, or phenyloxy-; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, aryl C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, aryl C 1 -C 6 alkoxycarbonyl, heteroarylcarbonyl, heteroaryl, heterocycloalkylcarbonyl, —C(O)N 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 5 )alkyl, haloalkyl or haloalkoxy; and
Z is absent, H, —NHC(O)aryl, —N(C 1 -C 4 alkyl)C(O)aryl, or aryl, wherein the aryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, or NO 2 , or
Z is —NHC(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl, or —N(C 1 -C 4 )alkyl-C(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 ) cycloalkyl.
31. A compound according to claim 30 selected from the group consisting of:
3-{[4′-[(2-butyl-1-benzofuran-3-yl) methyl]-4-(3-phenylpropoxy)biphenyl-3-yl]amino}-3-oxopropanoic acid;
4-{[4′-[(2-butyl-1-benzofuran-3-yl)methyl]-4-(3-phenylpropoxy)biphenyl-3-yl]amino}-4-oxobutanoic acid;
5-{[4′-[(2-butyl-1-benzofuran-3-yl)methyl]-4-(3-phenylpropoxy)biphenyl-3-yl]amino}-5-oxopentanoic acid;
N-[4-Benzyloxy-4′-(2-butyl-benzofuran-3-ylmethyl)-biphenyl-3-yl]-malonamic acid.
32. A compound of the formula:
wherein
n is 0, 1, 2, or 3;
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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;
R 1 is H, C 1 -C 6 alkyl, or benzyl;
R 21 and R 22 are independently selected from H, phenyl(C 1 -C 6 )alkoxy, phenyl(C 1 -C 6 )alkyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, and N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 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;
L 3 is a bond or —(C 1 -C 4 )alkyl-;
L 5 is —N(R 9 )C(O)—(C 1 -C 4 ) alkyl- or —N(R 9 )SO 2 —(C 1 -C 4 )alkyl-, wherein
R 9 independently is H, C 1 -C 6 alkyl, —SO 2 -phenyl, —C 1 -C 6 alkyl-furanyl, —C 1 -C 6 alkyl-tetrazolyl, —C 1 -C 6 alkyl thienyl, —C 1 -C 6 - alkyl pyrrolyl, —C 1 -C 6 - alkyl pyridyl, or benzyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy; and
Q is phenyl, phenyl-O-phenyl, indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 )alkyl-phenyl, -indolyl-(C 1 -C 4 )alkyl-phenyl, benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, or imidazo[2,1-b]thiazol-3-one, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, or phenyl-(C 1 -C 6 )alkyl-.
33. A compound according to claim 32 wherein R 1 and R 21 are both H; and
R 22 is H, phenyl(C 1 -C 6 )alkoxy, benzyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 2 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , CF 3 , or OCF 3 .
34. A compound according to claim 33 of the formula:
wherein
n is 0, 1, 2, or 3; and
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 6 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl.
35. A compound according to claim 33 of the formula:
wherein
n is 0, 1, 2, or 3; and
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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.
36. A compound according to claim 33 of the formula:
wherein
n is 0, 1, 2, or 3;
each R 10 , is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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 5 is alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, or phenyl.
37. A compound according to claim 33 of the formula:
wherein
n is 0, 1, 2, or 3; and
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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.
38. A compound of the formula:
wherein
n is 0, 1, 2, or 3;
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 6 haloalkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl;
R 1 is H, C 1 -C 6 alkyl, or benzyl;
R 21 and R 22 are independently selected from H, phenyl(C 1 -C 6 )alkoxy, phenyl(C 1 -C 6 )alkyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, and N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 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;
L 3 is a bond or —( C 1 -C 4 )alkyl-;
R 9 is H, C 1 -C 6 alkyl, —SO 2 -phenyl, —C 1 -C 6 alkyl-furanyl, —C 1 -C 6 alkyl-tetrazolyl, —C 1 -C 6 - alkyl thienyl , —C 1 -C 6 - alkyl pyrrolyl, —C 1 -C 6 - alkyl pyridyl, or benzyl, wherein the aryl and heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, C 1 -C 6 haloalkyl, or C 1 -C 4 haloalkoxy; and
Q is indolizinyl, benzofuranyl, indolyl, dibenzofuranyl, -benzothienyl-(C 1 -C 4 )alkyl-phenyl, -indolyl- (C 1 -C 4 ) alkyl-phenyl, benzofuranyl-(C 1 -C 4 ) alkyl-phenyl, or imidazo[2,1-b]thiazol-3-one, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, phenyl, or phenyl-(C 1 -C 6 )alkyl-.
39. A compound according to claim 38 wherein
R 1 and R 21 are both H; and
R 22 is H, phenyl(C 1 -C 6 )alkoxy, benzyl, halogen, (C 1 -C 6 )alkyl, C 1 -C 6 alkoxy, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, or N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, wherein the phenyl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , CF 3 , or OCF 3 .
40. A compound according to claim 38 of the formula:
wherein
n is 0, 1, 2, 3, or 4; and
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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.
41. A compound according to claim 38 of the formula:
wherein
n is 0, 1, 2, or 3; and
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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.
42. A compound according to claim 38 of the formula:
wherein
n is 0, 1, 2, or 3;
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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 5 is alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, or phenyl.
43. A compound according to claim 38 of the formula:
wherein
n is 0, 1, 2, or 3; and
each R 10 is independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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.
44. A compound according to claim 38 that is N-[3-Benzyloxy4′-(2-butyl-benzofuran-3-ylmethyl)-biphenyl-4-yl]-oxalamic acid
45. A pharmaceutical composition comprising a compound of claim 38 and at least one pharmaceutically acceptable solvent, carrier, adjuvant or excipient.
46. A compound of formula:
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, or C 2 -C 6 alkenyl;
L 3 is —(C 1 -C 4 )alkyl-O—,—O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, -alkenyl-, or -phenyl-;
R 9 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, —SO 2 -aryl, heteroarylalkyl, or arylalkyl, wherein the aryl or heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, haloalkyl, or haloalkoxy;
R 20 , R 22 , and R 23 are independently selected from H, arylalkoxy, arylalkyl, halogen, alkyl, alkoxy, NO 2 , NH 2 , CN, 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, and —N(C 1 -C 4 alkyl)SO 2 -aryl, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
R 21 is arylalkoxy, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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;
Q is aryl, -aryl-carbonyl-aryl, -aryl-O-aryl, -aryl-alkyl-aryl, -aryl-heteroaryl, -aryl-heterocycloalkyl, -heteroaryl, or -heteroaryl-alkyl-aryl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, phenyl-C 1 -C 6 alkyl-, or phenyloxy-; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, aryl C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, aryl C 1 -C 6 alkoxycarbonyl, heteroarylcarbonyl, heteroaryl, heterocycloalkylcarbonyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 )alkyl, —C(O)N(C 1 -C 5 )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; and
Z is absent, H, —NHC(O)aryl, —N(C 1 -C 4 alkyl)C(O)aryl, or aryl, wherein the aryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, or NO 2 , or
Z is —NHC(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl, or —N(C 1 -C 4 )alkyl-C(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl.
47. A compound according to 46 that is N-[4′-(2-Butyl-benzofuran-3-ylmethyl)-4-(3phenyl-propoxy)-biphenyl-3-yl]-oxalamic acid
48. A pharmaceutical composition comprising a compound of claim 46 and at least one pharmaceutically acceptable solvent, carrier, adjuvant or excipient.
49. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein,
R 1 is H, C 1 -C 6 alkyl, phenyl(C 1 -C 6 )alkyl, or C 2 -C 6 alkenyl;
L 3 is a bond, —(C 1 -C 4 )alkyl-O—, —O—(C 1 -C 4 )alkyl, —(C 1 -C 4 ) alkyl-, -alkenyl-, or -phenyl-;
R 9 is H, C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, —SO 2 -aryl, heteroarylalkyl, or arylalkyl, wherein the aryl or heteroaryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, NO 2 , NH 2 , NH(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl(C 1 -C 6 )alkyl, haloalkyl, or haloalkoxy;
R 20 , R 22 , and R 23 are independently selected from H, arylalkoxy, arylalkyl, halogen, alkyl, alkoxy, NO 2 , NH 2 , CN, 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, and —N(C 1 -C 4 alkyl)SO 2 -aryl, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
R 21 , is arylalkoxy, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NO 2 , haloalkyl, or haloalkoxy;
the A ring is phenyl, which is optionally substituted with 1, 2, or 3 groups that are independently, halogen, C 1 -C 6 alkyl, C 1 -C 6 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;
Q is aryl, -aryl-carbonyl-aryl, -aryl-O-aryl, -aryl-alkyl-aryl, -aryl-heteroaryl, -aryl-heterocycloalkyl, -heteroaryl, or -heteroaryl-alkyl-aryl, wherein the aforementioned cyclic groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkoxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, NR 6 R 7 , phenyl, phenyl-C 1 -C 6 alkyl-, or phenyloxy-; wherein
R 6 and R 7 are independently H, C 1 -C 6 alkyl, aryl(C 1 -C 6 )alkyl, C 2 -C 6 alkanoyl, aryl C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, aryl C 1 -C 6 alkoxycarbonyl, 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; and
Z is absent, H, —NHC(O)aryl, N(C 1 -C 4 alkyl)C(O)aryl, or aryl, wherein the aryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, haloalkyl, haloalkoxy, or NO 2 , or
Z is —NHC(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl, or —N(C 1 -C 4 )alkyl-C(O)—(C 1 -C 4 )alkyl-(C 3 -C 7 )cycloalkyl.
50. A pharmaceutical composition comprising a compound of claim 49 and at least one pharmaceutically acceptable solvent, carrier, adjuvant or excipient.