Synthesis and discovery of 2,3-dihydro-3,8-diphenylbenzo[1,4]oxazines as a novel class of potent cholesteryl ester transfer protein inhibitors.

Abstract 2,3-Dihydro-3,8-diphenylbenzo[1,4]oxazines were identified as a new class of potent cholesteryl ester transfer protein inhibitors. The most potent compound 6a (IC 50  = 26 nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat ( F  = 53%) and long human liver microsome stability ( t 1/2  = 62 min). It increased HDL-C in human CETP transgenic mice and high-fat fed hamsters. The structure and activity relationship of this series will be described in this Letter.