Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh & McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA.
Bioorg Med Chem Lett. 2010 Feb 15;20(4):1432-5. doi: 10.1016/j.bmcl.2009.12.096. Epub 2010 Jan 4.
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.
2,3-二氢-3,8-二苯基苯并[1,4]恶嗪被鉴定为一类新型强效胆固醇酯转移蛋白抑制剂。最有效的化合物 6a（IC50=26 nM）具有良好的药代动力学特性，在大鼠（F=53%）中具有良好的口服生物利用度，并且人肝微粒体稳定性长（t(1/2)=62 min）。它能增加人 CETP 转基因小鼠和高脂喂养仓鼠的 HDL-C。本函将描述该系列的结构和活性关系。
