Preparation of pyridazine carboxamides as inhibitors of stearoyl-CoA desaturase.

Abstract

Title compds. represented by the formula I [wherein G = N(R4), O, S, SO, etc.; L, M = independently -N=, -C(R4)= or -C(R4)=C(R4)-; R2 = (hydroxy)alkyl, alkenyl, heterocyclyl, etc.; R3 = (cyclo)alkyl, alkenyl, aralkyl, etc.; R4 = independently H, F, Cl, alkyl, etc.; m, n = independently 0-3; J, K = N or (un)substituted C; V = a direct bond, (un)substituted amino, O, etc.; W = a direct bond, O, (alkyl)amino, etc.; Q = N(R4), O, S, SO or SO2; 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, II was provided in a multi-step synthesis starting from 3-chloro-6-methylpyridazine. 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)]