4-(2-Pyridyl)piperazine-1-benzimidazoles as potent TRPV1 antagonists

被引：44

作者：

Shao, B ^{[1
]}

Huang, JC ^{[1
]}

Sun, Q ^{[1
]}

Valenzano, KJ ^{[1
]}

Schmid, L ^{[1
]}

Nolan, S ^{[1
]}

机构：

[1] Purdue Pharma LP, Cranbury, NJ 08512 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 03期

关键词：

D O I：

10.1016/j.bmcl.2004.11.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-(2-pyridyl)piperazine-1-benzimidazole analogues based on compound I was synthesized and evaluated for TRPV1 antagonist activity in capsaicin-induced (CAP) and pH5.5-induced (pH) FLIPR assays in a human TRPV1 -expressing HEK293 cell line. Potent TRPV1 antagonists were identified through SAR studies. From these studies, several antagonists were found, with IC50 values ranging from 32nM to similar to5000nM. Among these, 11 [IC50 = 90nM (CAP) and 104nM (pH)] was further evaluated and found to be orally available in rats (F% = 19.7). (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：719 / 723

页数：5

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