Preparation of substituted thiazole derivatives for use as stearoyl-CoA desaturase inhibitors.

Abstract

Title compds. I [Q = (un)substituted oxoimidazolidine or oxotriazole; V = bond, C(O), S(O), etc.; W = O, S, S(O), OC(O), etc.; R1 = H, halo, alkyl, aryl, etc.; R2 = H, alkyl, cycloalkyl, aryl, etc.; or R1 and R2 independently = a multi-ring structure having 2 to 4 rings where in the rings are independently cycloalkyl, heterocyclyl, aryl, or heteroaryl and where some or all of the rings may be fused to each other; R3 = H or alkyl], and their pharmaceutically acceptable salts, are prepd. and disclosed as stearoyl-CoA desaturase inhibitors. Thus, e.g., II was prepd. by protection of Et 2-amino-4-methylthiazole-5-carboxylate followed by alkylation with N-Boc-(R)-1-amino-2-propanol, deprotection, cyclization with phosgene, alkylation with 4-fluorobenzyl bromide, hydrolysis, and amidation with ammonium chloride. Select I were evaluated in stearoyl-CoA desaturase inhibition assays (data given). [on SciFinder(R)]