Compounds and methods to treat cardiac failure and other disorders

摘要

The invention is directed to compounds of the formula and the pharmaceutically acceptable salts thereof wherein Ar1 is indole, benzimidazole, or benzotriazole, optionally substituted with lower alkyl (1-4C), halo, or lower alkoxy (1-4C); X1 is CO or an isostere thereof; Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl; n is 0 or 1; Z is CH or N; X2 is CH, CH2 or an isostere thereof; and Ar2 consists of one or two phenyl moieties directly coupled to X2 and optionally substituted by halo, nitro, alkyl (1-6C), CN or CF3, or by RCO, COOR, CONR2, NR2, OR or SR, wherein R is H or alkyl (1-6C) or by phenyl, itself optionally substituted by the foregoing substituents; with the proviso that if Z is N, X1 is CO, and Ar1 is indole, Ar1 must be coupled to X1 through the 2, 5-, 6- or 7-position. These compounds are useful in the treatment of conditions associated with inflammation. In addition, the above compounds and other compounds described herein are useful in treating conditions associated with cardiac failure.