Preparation of piperazinyl benzamide derivatives as stearoyl-CoA desaturase inhibitors.

Abstract

Title compds. represented by the formula I [wherein m, n = independently 0-3; J, K = independently N or (un)substituted C; V = a direct bond, (un)substituted amino, O, etc.; W = CN, alkoxy, alkylamino, etc.; R3 = H, (cycloalkyl)alkyl, heterocyclyl, etc.; R4 = H, F, Cl, (halo)alkyl, etc.; R5, R5a, R6, R6a, R7, R7a, R8, R8a = independently H or alkyl or R5R5a = O, etc.; and their stereoisomers, enantiomers, tautomers or mixt. of stereoisomers, as pharmaceutically acceptable salts or prodrugs thereof] were prepd. as stearoyl-CoA desaturase (SCD) inhibitors. For example, amidation of 4-bromobenzoyl chloride with (2-cyclopropylethyl)amine and followed by coupling reaction with (piperazin-1-yl)(2-trifluoromethylphenyl)methanone gave II in 28% yield. I showed activity as inhibitors of SCD in the assay of incubation of mouse liver microsomes. Thus, I and their pharmaceutical compns. are useful as SCD inhibitors for the treatment of SCD-mediated disease or condition, such as type II diabetes, impaired glucose and insulin resistance (no data). [on SciFinder(R)]