Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 230, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2021.114027
Keywords
Cannabinoids; SAR studies; Nabilone analogs; CB1 receptor
Categories
Funding
- National Institute on Drug Abuse [DA009158, DA041435]
Ask authors/readers for more resources
This study merged the features of nabilone and AM2389 and optimized the C3 side chain. Among the nabilone analogs, AM8936 exhibited balanced and potent agonist activity on the CB1 receptor, making it a potential candidate for further development.
In earlier work, we explored the SAR for the C3 side chain pharmacophore in the hexahydrocannabinol template represented by the drug nabilone, which resulted in the development of AM2389. In an effort for further optimization, we have merged features of nabilone and AM2389 and explored the C3 side chain with varying chain lengths and terminal substitutions. Of the compounds described here, a nabilone analog, AM8936, with the C6'-cyano-substituted side chain, was identified as the most successful analog capable of serving as a potential candidate for further development and a valuable tool for further in vivo studies. AM8936 behaved as a balanced and potent CB1 agonist in functional assays and was a potent and efficacious CB1 agonist in vivo. Our SAR studies are highlighted with the docking of AM8936 on the crystal structure of the hCB1 receptor. (C) 2021 Published by Elsevier Masson SAS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available