Published March 2, 2017
| Version v1
Journal article
Open
Discovery and pharmacological evaluation of a novel series of adamantyl cyanoguanidines as P2X7 receptor antagonists.
Creators
- 1. School of Chemistry, The University of Sydney, NSW 2006 Australia
- 2. School of Medical Sciences, The University of Sydney, NSW 2006 Australia
- 3. Faculty of Health Sciences, The University of Sydney, NSW 2006 Australia
- 4. Charles Perkins Centre, The University of Sydney, NSW 2006 Australia
- 5. School of Pharmacy and Medical Sciences, University of South Australia, SA 5001 Australia
Description
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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O'Brien-Brown_EurJMedChem_2017-P19-AAM.pdf
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