Preparation of piperazine derivatives as stearoyl-CoA desaturase inhibitors for the treatment of diabetes and other diseases.

Abstract

Title compds. I [wherein x, y = 1-3; W = N(R1)C(O), C(O)N(R1), O, S or S(O)2; V = C(O/S) or C(R10)H; G, J, L, M = N or C(R4); R1 = H or (un)substituted alkyl; R2, R3 = (un)substituted alk(en)yl, (hetero)aryl or heterocyclyl; R4 = H, F, Me, OMe or cyano; R5, R5a, R6, R6a, R7, R7a, R8, R8a, R10 = H or alkyl; etc., and stereoisomers, enantiomers or tautomers, pharmaceutically acceptable salts, pharmaceutical compns. or prodrugs thereof] were prepd. as stearoyl-CoA desaturase (SCD) inhibitors. For example, amidation of 2-chloro-4-trifluoromethylpyrimidine-5-carbonyl chloride with 3-methylbutylamine (70% yield) followed by substitution with piperazine gave a monofunctionlized piperazine (86% yield). This compd. underwent benzoylation with 2-trifluoromethylbenzoyl chloride to afford piperazinylpyrimidine II (76% yield). I and their pharmaceutical compns. are useful in the treatment or prevention of various human diseases, including those mediated by stearoyl-CoA desaturase (SCD) enzymes, esp. diseases related to elevated lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like. [on SciFinder(R)]