Structure−Activity Relationship Studies on N′-Aryl Carbohydrazide P2X7 Antagonists
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- 作者：Derek W. Nelson ; Kathy Sarris ; Douglas M. Kalvin ; Marian T. Namovic ; George Grayson ; Diana L. Donnelly-Roberts ; Richard Harris ; Prisca Honore ; Michael F. Jarvis ; Connie R. Faltynek ; William A. Carroll
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：May 22, 2008
- 年：2008
- 卷：51
- 期：10
- 页码：3030 - 3034
- 全文大小：88K
- 年卷期：v.51,no.10(May 22, 2008)
- ISSN：1520-4804
文摘
N′-Aryl acyl hydrazides were identified as P2X7 receptor antagonists. Structure−activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X7 receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1β. Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain.