Discovery and optimization of a novel series of liver X receptor-α agonists

被引：51

作者：

Li, LP

Liu, JW

Zhu, LS

Cutler, S

Hasegawa, H

Shan, B

Medina, JC

机构：

[1] Amgen Inc, San Francisco, CA 94080 USA

[2] Dainippon Sumitomo Pharma Co Ltd, Konohana Ku, Osaka 5540022, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 06期

关键词：

hexafluorocarbinol; liver X receptor-alpha; LXR alpha agonist; T0901317; cholesterol transporter;

D O I：

10.1016/j.bmcl.2005.12.015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of hexafluorocarbinols were discovered as potent activators of the liver X receptor-alpha using a fluorescence polarization assay. Structure-activity relationship study led to the identification of compounds that are more potent agonists than the endogenous ligand, 24(S), 25-epoxycholesterol, with similar efficacy. Several compounds, including T0901317, were shown to have desirable pharmacokinetic profiles suitable for in vivo studies. (C) 2005 Elsevier Ltd. All rights reserved.

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收藏

页码：1638 / 1642

页数：5

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