MEDI 423 |
| Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that mediates the transfer of cholesteryl ester from high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) with a reciprocal exchange of triglyceride. Recently, small-molecule CETP inhibitors have been shown to raise HDL cholesterol and slow the progression of atherosclerosis in animal models and humans. In a continuation of our effort in the atherosclerosis arena, we discovered a series of heteroaromatic fused piperidines as CETP inhibitors. Herein we describe our SAR effort for a novel series 1,5-napthyridines as CETP inhibitors, within this series we examined the structure-activity-relationships depicted in I . This effort lead to the identification of II with in vitro human plasma CETP inhibitory activity (IC50) in the 10-8 M range. The in vitro and in vivo SAR of this series will be described.
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General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Division of Medicinal Chemistry |
