Discovery and SAR of cinnolines/quinolines as liver X receptor (LXR) agonists with binding selectivity for LXRβ

被引：45

作者：

Hu, Baihua ^{[1
]}

Unwalla, Raymound ^{[1
]}

Collini, Michael ^{[1
]}

Quinet, Elaine ^{[2
]}

Feingold, Irene ^{[3
]}

Goos-Nilsson, Annika ^{[4
]}

Wihelmsson, Anna ^{[4
]}

Nambi, Ponnal ^{[2
]}

Wrobel, Jay ^{[1
]}

机构：

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

[2] Wyeth Res, Cardiovasc & Metab Dis, Collegeville, PA USA

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

[4] Karo Bio, Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 10期

关键词：

Liver X receptor (LXR); LXR beta binding selective agonists; Cinnoline; Quinoline; ACID BASED QUINOLINES; ACCURATE DOCKING; ATHEROSCLEROSIS; MODULATORS; ALPHA; GLIDE;

D O I：

10.1016/j.bmc.2009.04.012

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 cinnolines/quinolines was prepared and it was found that 4-phenyl-cinnoline/quinolines with either a 2',3' or 2',5'-disubstituted benzyloxy moiety or the 1-Me-7-indole methoxy moiety on the meta position of the 4-phenyl ring showed good binding selectivity for LXR beta over LXR alpha. The LXR beta binding selective modulators displayed good activity for inducing ABCA1 gene expression in J774 macrophage cell line and poor efficacy in the LXR alpha Gal4 functional assay. 26, 37 and 41 were examined for their ability to induce SREBP-1c gene expression in Huh-7 liver cell line and they were weak partial agonists. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3519 / 3527

页数：9

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