1-(3-Aryloxyaryl)benzimidazole sulfones are liver X receptor agonists

被引：29

作者：

Travins, Jeremy M. ^{[1
]}

Bernotas, Ronald C. ^{[1
]}

Kaufman, David H. ^{[1
]}

Quinet, Elaine ^{[2
]}

Nambi, Ponnal ^{[2
]}

Feingold, Irene ^{[3
]}

Huselton, Christine ^{[3
]}

Wilhelmsson, Anna ^{[4
]}

Goos-Nilsson, Annika ^{[4
]}

Wrobel, Jay ^{[1
]}

机构：

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

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

[3] Wyeth Pharmaceut, Drug Safety & Metab, Collegeville, PA 19426 USA

[4] Karo Bio AB, Novum, S-14157 Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 02期

关键词：

Benzimidazole; Sulfone; ABCA1; LXR; Liver X receptor; Cholesterol; Lipid; Atherosclerosis; COUPLING REACTION; ARYL HALIDES; LXR-ALPHA; BENZIMIDAZOLES; INFLAMMATION; CHOLESTEROL; METABOLISM; MODULATORS; QUINOLINES; ARYLATION;

D O I：

10.1016/j.bmcl.2009.11.099

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1-(3-aryloxyaryl)benzimidazoles incorporating a sulfone substituent (6) was prepared. High affinity LXR ligands were identified (LXR beta binding IC50 values <10 nM), some with excellent agonist potency and efficacy in a functional assay of LXR activity measuring ABCA1 mRNA increases in human macrophage THP1 cells. The compounds were typically stable in liver microsome preparations and had good oral exposure in mice. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：526 / 530

页数：5

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