Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives

被引：36

作者：

Watson, Robert J. ^{[1
]}

Allen, Daniel R. ^{[1
]}

Birch, Helen L. ^{[1
]}

Chapman, Gayle A. ^{[1
]}

Galvin, Frances C. ^{[1
]}

Jopling, Louise A. ^{[1
]}

Knight, Roland L. ^{[1
]}

Meier, Dorica ^{[1
]}

Oliver, Kathryn ^{[1
]}

Meissner, Johannes W. G. ^{[1
]}

Owen, David A. ^{[1
]}

Thomas, Elizabeth J. ^{[1
]}

Tremayne, Nell ^{[1
]}

Williams, Sophie C. ^{[1
]}

机构：

[1] UCB Inflammat Discovery, Cambridge CB21 6GS, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 01期

关键词：

CXCR3; antagonists; piperidine urea; tropanyl urea;

D O I：

10.1016/j.bmcl.2007.10.109

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimization of a series of 1-aryl-3-piperidinyl urea derivatives is described in which incorporation of tropenyl and homotropenyl moieties has led to significant improvements in activity and drug-like properties. Replacement of the central piperidine with an exo-tropanyl unit led to the identification of compound 15 which provides a combination of excellent potency against human and murine receptors, drug-like properties and pharmacokinetics, thus providing a valuable tool for the evaluation of CXCR3 antagonists in models of human disease. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：147 / 151

页数：5

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