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

…, PD Pelton, M Yong, KT Demarest, WV Murray…

Index: Wang, Aihua; Prouty, Catherine P.; Pelton, Patricia D.; Yong, Maria; Demarest, Keith T.; Murray, William V.; Kuo, Gee-Hong Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 4 p. 1432 - 1435

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Citation Number: 18

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 (IC50= 26nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat (F= 53%) and long human liver microsome stability (t1/2= 62min). It increased HDL-C in human CETP transgenic mice and high-fat fed hamsters. The structure and activity relationship of this ...