Preparation of 4,5-dihydro-3H-spiro[benzo[b][1,4]oxazepine-2,4'-piperidine] derivatives as stearoyl-CoA delta-9 desaturase inhibitors.

Abstract

Title compds. I [R1 = (un)substituted aryl or heteroaryl; R2 = (un)substituted heteroaryl; each R3 independently = alkyl, alkoxy or halo; each R4 and R5 independently = alkyl or halo; m = 0-4; n = 1-3; p = 0-4; q = 0-1], and their pharmaceutically acceptable salts, are prepd. and disclosed. Thus, e.g., II was prepd. by reaction of 5-(3-(trifluoromethyl)benzyl)-4,5-dihydro-3H-spiro[benzo[b][1,4]oxazepine-2,4'-piperidine] dihydrochloric acid (prepn. given) with Me 2-bromothiazole-5-carboxylate. Compds. of the invention were tested for their inhibition activity of stearoyl-CoA delta-9 desaturase, e.g., II exhibited IC50 value of ranging from 0.5 nM to 49 nM. The invention compds. are useful for treating or preventing disorders such as non-insulin dependent (Type 2) diabetes, obesity, hyperglycemia, etc. [on SciFinder(R)]