Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists
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Date
2017
Authors
O'Brien Brown, J.
Jackson, A.
Reekie, T.A.
Barron, M.L.
Werry, E.L.
Schiavini, P.
McDonnell, M.
Munoz, L.
Wilkinson, S.
Noll, B.
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European Journal of Medicinal Chemistry, 2017; 130:433-439
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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.
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Data source: Appendix A. Supplementary data, http://www.sciencedirect.com/science/MiamiMultiMediaURL/1-s2.0-S0223523417301459/1-s2.0-S0223523417301459-mmc1.docx/271932/html/S0223523417301459/b62a7f01410e5ee36e7bec03420c1115/mmc1.docx
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Copyright 2017 Elsevier Masson SAS
Access Condition Notes: post print available after 1 April 2019