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

详细信息    查看全文

• 作者：Paul J. Beswick ; Andy Billinton ; Laura J. Chambers ; David K. Dean ; Elena Fonfria ; Robert J. Gleave ; Stephen J. Medhurst ; Anton D. Michel ; Andrew P. Moses ; Sadhana Patel ; Shilina A. Roman ; Sue Roomans
• 关键词：P2X₇ ; SAR ; Pain
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 August 2010
• 年：2010
• 卷：20
• 期：15
• 页码：4653-4656
• 全文大小：380 K

文摘

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 antihyperalgesic 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].