Further modification on phenyl acetic acid based quinolines as liver X receptor modulators

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• 作者：Baihua Hu ; James Jetter ; David Kaufman ; Robert Singhaus ; Ronald Bernotas ; Rayom ; Unwalla ; Elaine Quinet ; Dawn Savio ; Anita Halpern ; Michael Basso ; et al.
• 关键词：Liver X receptor (LXR) ; LXR agonists ; Quinoline ; Phenyl acetic acid
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 May 2007
• 卷：15
• 期：10
• 页码：3321-3333
• 文件大小：260 K

摘要

A series of phenyl acetic acid based quinolines was prepared as LXR modulators. An SAR study in which the C-3 and C-8 positions of the quinoline core were varied led to the identification of two potent LXR agonists trong>23trong> and trong>27trong>. Both compounds displayed good binding affinity for LXRβ and LXRα, and increased expression of ABCA1 in THP-1 cells. These two compounds also had desirable pharmacokinetic profiles in mice and displayed in vivo efficacy in a 12-week Apo E knockout mouse lesion model.