Discovery of DF-461, a Potent Squalene Synthase Inhibitor

ACS Med Chem Lett. 2013 Sep 4;4(10):932-6. doi: 10.1021/ml400151c. eCollection 2013 Oct 10.

Abstract

We report the development of a new trifluoromethyltriazolobenzoxazepine series of squalene synthase inhibitors. Structure-activity studies and pharmacokinetics optimization on this series led to the identification of compound 23 (DF-461), which exhibited potent squalene synthase inhibitory activity, high hepatic selectivity, excellent rat hepatic cholesterol synthesis inhibitory activity, and plasma lipid lowering efficacy in nonrodent repeated dose studies.

Keywords: Squalene synthase; dyslipidemia; inhibitor; triazolobenzoxazepine.