Discovery and biological evaluation of novel cyanoguanidine P2X7 antagonists with analgesic activity in a rat model of neuropathic pain

A Perez-Medrano, DL Donnelly-Roberts…

Index: Perez-Medrano, Arturo; Donnelly-Roberts, Diana L.; Honore, Prisca; Hsieh, Gin C.; Namovic, Marian T.; Peddi, Sridhar; Shuai, Qi; Wang, Ying; Faltynek, Connie R.; Jarvis, Michael F.; Carroll, William A. Journal of Medicinal Chemistry, 2009 , vol. 52, # 10 p. 3366 - 3376

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Citation Number: 42

Abstract

We disclose the design of a novel series of cyanoguanidines that are potent (IC50≃ 10− 100 nM) and selective (≥ 100-fold) P2X7 receptor antagonists against the other P2 receptor subtypes such as the P2Y2, P2X4, and P2X3. We also found that these P2X7 antagonists effectively reduced nociception in a rat model of neuropathic pain (Chung model). Particularly, analogue 53 proved to be effective in the Chung model, with an ED50 of 38 ...