Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists

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.

The synthesis and in vitro characterization of a series of phenyltriazole P2X7 antagonists are described. Compound 12 was discovered to be active in a rat model of neuropathic pain.Figure optionsDownload as PowerPoint slide