Novel and potent 3-(2, 3-dichlorophenyl)-4-(benzyl)-4H-1, 2, 4-triazole P2X 7 antagonists

…, DL Donnelly-Roberts, MT Namovic, G Grayson…

Index: Carroll, William A.; Kalvin, Douglas M.; Perez Medrano, Arturo; Florjancic, Alan S.; Wang, Ying; Donnelly-Roberts, Diana L.; Namovic, Marian T.; Grayson, George; Honore, Prisca; Jarvis, Michael F. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 14 p. 4044 - 4048

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Citation Number: 42

Abstract

Structure–activity relationship (SAR) studies were conducted around early tetrazole-based leads 3 and 4. Replacements for the tetrazole core were investigated and the pendant benzyl substitution was reoptimized with a triazole isostere. Triazole-based P2X7 antagonists were identified with similar potency to the lead compound 4 but with improved physiochemical properties. Compound 12 was active in a rat model of neuropathic pain.

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