Biarylether amide quinolines as liver X receptor agonists

被引：43

作者：

Bernotas, Ronald C. ^{[1
]}

Singhaus, Robert R. ^{[1
]}

Kaufman, David H. ^{[1
]}

Ullrich, John ^{[1
]}

Fletcher, Horace, III ^{[1
]}

Quinet, Elaine ^{[2
]}

Nambi, Ponnal ^{[2
]}

Unwalla, Rayomand ^{[1
]}

Wilhelmsson, Anna ^{[3
]}

Goos-Nilsson, Annika ^{[3
]}

Farnegardh, Mathias ^{[3
]}

Wrobel, Jay ^{[1
]}

机构：

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

[2] Wyeth Pharmaceut, Cardiovasc & Metab Dis, Collegeville, PA 19426 USA

[3] Karo Bio AB, S-14157 Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 04期

关键词：

Liver X receptor; LXR; Agonist; Quinoline; ABCA1; LXR-ALPHA; CHOLESTEROL; MODULATORS; ACTIVATION; LIGAND; ACIDS;

D O I：

10.1016/j.bmc.2008.12.048

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 4-(amido-biarylether)-quinolines was prepared as potential LXR agonists. Appropriate substitution with amide groups provided high affinity LXR ligands, some with excellent potency and efficacy in functional assays of LXR activity. Novel amide 4g had a binding IC50 = 1.9 nM for LXRb and EC50 = 34 nM (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide substitution are potent LXR agonists (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1663 / 1670

页数：8

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