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ID: ALA4011591
Journal: Eur J Med Chem
Title: Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists.
Authors: O'Brien-Brown J, Jackson A, Reekie TA, Barron ML, Werry EL, Schiavini P, McDonnell M, Munoz L, Wilkinson S, Noll B, Wang S, Kassiou M.
Abstract: Here we report adamantyl cyanoguanidine compounds based on hybrids of the adamantyl amide scaffold reported by AstraZeneca and cyanoguanidine scaffold reported by Abbott Laboratories. Compound 27 displayed five-fold greater inhibitory potency than the lead compound 2 in both pore-formation and interleukin-1β release assays, while 35-treated mice displayed an antidepressant phenotype in behavioral studies. This SAR study provides a proof of concept for hybrid compounds, which will help in the further development of P2X7R antagonists.
CiteXplore: 28279849