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Bioorg Med Chem Lett. 2007 Jul 15;17(14):4044-8. Epub 2007 Apr 27.

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

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  • 1Abbott Laboratories, Neuroscience Research, 100 Abbott Park Road, Abbott Park, IL 60064, USA.


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 P2X(7) 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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