Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists
| Main Authors: | O'Brien-Brown, James, Jackson, Alexander, Reekie, Tristan A, Barron, Melissa L, Werry, Eryn L, Schiavini, Paolo, McDonnell, Michelle, Munoz, Lenka, Wilkinson, Shane, Noll, Benjamin, Wang, Shudong, Kassiou, Michael |
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| Format: | Article |
| Terbitan: |
, 2017
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/400509 |
Daftar Isi:
- 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.