Quinolinyl glucagon receptor modulators

摘要

The present invention provides a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, A1, A2, A3, B1, B2, B3 and B4 are as defined herein. The compounds of Formula I have been found to act as glucagon antagonists or inverse agonists. Consequently, the compounds of Formula I and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucagon.;

主权项

1. A compound of Formula Ior a pharmaceutically acceptable salt thereof, wherein
R1 is (C1-C6)alkyl which is optionally substituted with one to three fluoro, hydroxy or methoxy; (C3-C7)cycloalkyl which is optionally substituted with one to two fluoro or one to two (C1-C3)alkyl which are each optionally substituted with one to three fluoro and wherein one carbon of the (C3-C7)cycloalkyl can be replaced with an O; or (C3-C7)cycloalkyl-(C1-C6)alkyl wherein the (C3-C7)cycloalkyl group of said (C3-C7)cycloalkyl-(C1-C6)alkyl is optionally substituted with one to two (C1-C3)alkyl which are each optionally substituted with one to three fluoro; R2 is hydrogen or (C1-C3)alkyl; R3 is tetrazolyl, —CH2-tetrazolyl, —(CH2)2SO3H, —(CH2)2CO2H, —CH2CHFCO2H or —CH2CH(OH)CO2H; One of A1, A2 and A3 is N and the remaining two of A1, A2 and A3 are CR4; R4 at each occurrence is independently hydrogen, halo, cyano, (C1-C3)alkyl optionally substituted with one to three fluoro, (C1-C3)alkoxy optionally substituted with one to three fluoro, or (C3-C5)cycloalkyl; B1, B2, B3 and B4 are each independently CR5; and R5 at each occurrence is independently hydrogen, halo, cyano, (C1-C3)alkyl optionally substituted with one to three fluoro, or (C1-C3)alkoxy optionally substituted with one to three fluoro, or (C3-C5)cycloalkyl.