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ID: ALA1221272

Journal: Bioorg Med Chem Lett

Title: Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

Authors: Abdi MH, Beswick PJ, Billinton A, Chambers LJ, Charlton A, Collins SD, Collis KL, Dean DK, Fonfria E, Gleave RJ, Lejeune CL, Livermore DG, Medhurst SJ, Michel AD, Moses AP, Page L, Patel S, Roman SA, Senger S, Slingsby B, Steadman JG, Stevens AJ, Walter DS.

Abstract: A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies.

CiteXplore: 20673717

DOI: 10.1016/j.bmcl.2010.07.033