Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists

被引：40

作者：

Tafesse, L ^{[1
]}

Sun, Q ^{[1
]}

Schmid, L ^{[1
]}

Valenzano, KJ ^{[1
]}

Rotshteyn, Y ^{[1
]}

Su, X ^{[1
]}

Kyle, DJ ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 22期

关键词：

D O I：

10.1016/j.bmcl.2004.09.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A structurally biased chemical library of pyridazinylpiperazine analogs was prepared in an effort to improve the pharmaceutical and pharmacological profile of the lead compound N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide (BCTC). The library was evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH 5.5-induced (pH) FLIPR assays in a human VR1-expressing HEK293 cell line. The most potent VR1 antagonists were found to have IC50 values in the range of 9-200nM with improved pharmaceutical and pharmacological profiles versus the lead BCTC. These compounds represent possible second-generation BCTC analogs. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：5513 / 5519

页数：7

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