4-(2-pyridyl)piperazine-1-carboxamides: Potent vanilloid receptor 1 antagonists

被引：41

作者：

Sun, Q ^{[1
]}

Tafesse, L ^{[1
]}

Islam, K ^{[1
]}

Zhou, XM ^{[1
]}

Victory, SF ^{[1
]}

Zhang, CW ^{[1
]}

Hachicha, M ^{[1
]}

Schmid, LA ^{[1
]}

Patel, A ^{[1
]}

Rotshteyn, Y ^{[1
]}

Valenzano, KJ ^{[1
]}

Kyle, DJ ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(03)00759-5

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-carboxamide analogues based on the lead compound 1 was synthesized and evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH (5.5)-induced (pH) FLIPR assays in a rat VR1-expressing HEK293 cell line. Potent VR1 antagonists were identified through SAR studies. From these studies, 18 was found to be very potent in the in vitro assay [IC50 = 4.8 nM (pH) and 35 nM (CAP)] and orally available in rat (F% = 15.1). (C) 2003 Elsevier Ltd. All rights reserved.

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页码：3611 / 3616

页数：6

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