| Literature DB >> 28279849 |
James O'Brien-Brown1, Alexander Jackson2, Tristan A Reekie1, Melissa L Barron3, Eryn L Werry3, Paolo Schiavini1, Michelle McDonnell2, Lenka Munoz4, Shane Wilkinson1, Benjamin Noll5, Shudong Wang5, Michael Kassiou6.
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.Entities:
Keywords: ATP; Adamantane; Adamantyl; Alzheimer's; IL-1β; Inflammation; Neurodegenerative; P2X receptor; P2X(7)R antagonist
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Year: 2017 PMID： 28279849 DOI： 10.1016/j.ejmech.2017.02.060
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514