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

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• 作者：Aihua Wang ; Catherine P. Prouty ; Patricia D. Pelton ; Maria Yong ; Keith T. Demarest ; William V. Murray ; Gee-Hong Kuo
• 关键词：Cholesteryl ester transfer protein ; CETP ; CETP inhibitors ; HDL-C ; Atherosclerosis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 February 2010
• 年：2010
• 卷：20
• 期：4
• 页码：1432-1435
• 全文大小：517 K

文摘

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 = 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.