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

被引：31

作者：

Hu, Baihua

Jetter, James

Kaufman, David

Singhaus, Robert

Bernotas, Ronald

Unwalla, Rayomand

Quinet, Elaine

Savio, Dawn

Halpern, Anita

Basso, Michael

Keith, James

Clerin, Valerie

Chen, Liang

Liu, Qiang-Yuan

Feingold, Irene

Huselton, Christine

Azam, Farooq

Goos-Nilsson, Annika

Wilhelmsson, Anna

Nambi, Ponnal

Wrobel, Jay

机构：

[1] Wyeth Pharmaceut, Chem & Screening Sci, Collegeville, PA 19426 USA

[2] Wyeth Pharmaceut, Cardiovasc & Metab Disorders, Collegeville, PA USA

[3] Wyeth Pharmaceut, Bio Transformat & Disposit, Collegeville, PA USA

[4] Karobio, Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 10期

关键词：

liver X receptor (LXR); LXR agonists; quinoline; phenyl acetic acid;

D O I：

10.1016/j.bmc.2007.03.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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 23 and 27. Both compounds displayed good binding affinity for LXR beta and LXR alpha, and increased expression of ABCAl 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. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：3321 / 3333

页数：13

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