Discovery and optimization of a series of liver X receptor antagonists

被引：16

作者：

Jiao, XianYun ^{[1
]}

Kopecky, David J. ^{[1
]}

Fisher, Ben ^{[1
]}

Piper, Derek E. ^{[2
]}

Labelle, Marc ^{[1
]}

McKendry, Sharon ^{[1
]}

Harrison, Martin ^{[2
]}

Jones, Stuart ^{[2
]}

Jaen, Juan ^{[1
]}

Shiau, Andrew K. ^{[3
]}

Escaron, Patrick ^{[3
]}

Danao, Jean ^{[3
]}

Chai, Anne ^{[3
]}

Coward, Peter ^{[3
]}

Kayser, Frank ^{[1
]}

机构：

[1] Amgen Inc, Dept Med Chem, San Francisco, CA 94080 USA

[2] Amgen Inc, Dept Mol Struct & Characterizat, San Francisco, CA 94080 USA

[3] Amgen Inc, Dept Metab Disorders, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 18期

关键词：

LXR alpha/beta; Antagonist; GAL4 reporter gene assay; mSREBP-1c reporter; Conversion; LXR-ALPHA; DEFICIENT MICE; CHOLESTEROL; GENE; LIGAND; BETA; AGONISTS; ATHEROSCLEROSIS; MODULATORS; PROMOTER;

D O I：

10.1016/j.bmcl.2012.07.048

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR alpha/beta) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents. (C) 2012 Published by Elsevier Ltd.

引用

页码：5966 / 5970

页数：5

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