Document Report Card

ID: ALA1145375

Journal: J Med Chem

Title: Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors.

Authors: Liu G, Lynch JK, Freeman J, Liu B, Xin Z, Zhao H, Serby MD, Kym PR, Suhar TS, Smith HT, Cao N, Yang R, Janis RS, Krauser JA, Cepa SP, Beno DW, Sham HL, Collins CA, Surowy TK, Camp HS.

Abstract: Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.

CiteXplore: 17530838

DOI: 10.1021/jm070219p