Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor

被引：24

作者：

Beswick, Paul J. ^{[1
]}

Billinton, Andy ^{[1
]}

Chambers, Laura J. ^{[1
]}

Dean, David K. ^{[1
]}

Fonfria, Elena ^{[1
]}

Gleave, Robert J. ^{[1
]}

Medhurst, Stephen J. ^{[1
]}

Michel, Anton D. ^{[1
]}

Moses, Andrew P. ^{[1
]}

Patel, Sadhana ^{[1
]}

Roman, Shilina A. ^{[1
]}

Roomans, Sue ^{[1
]}

Senger, Stefan ^{[1
]}

Stevens, Alexander J. ^{[1
]}

Walter, Daryl S. ^{[1
]}

机构：

[1] GlaxoSmithKline, Neurosci Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

关键词：

P2X(7); SAR; Pain; PAIN; MODEL;

D O I：

10.1016/j.bmcl.2010.05.107

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity relationships (SAR) of analogues of lead compound 1 were investigated and compound 16 was selected for further study in animal models of pain. Compound 16 was shown to be a potent anti-hyperalgesic agent in both the rat acute complete Freund's adjuvant (CFA) model of inflammatory pain [Iadarola, M. J.; Douglass, J.; Civelli, O.; Naranjo, J. R. rain Res. 1988, 455, 205] and the knee joint model of chronic inflammatory pain [Wilson, A. W.; Medhurst, S. J.; Dixon, C. I.; Bontoft, N. C.; Winyard, L. A.; Brackenborough, K. T.; De Alba, J.; Clarke, C. J.; Gunthorpe, M. J.; Hicks, G. A.; Bountra, C.; McQueen, D. S.; Chessell, I. P. Eur. J. Pain 2006, 10, 537]. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4653 / 4656

页数：4

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