AI Article Synopsis
- - This research builds on previous studies of the C3 side chain pharmacophore using the drug nabilone, which led to the creation of a new compound, AM2389.
- - The team merged characteristics of nabilone and AM2389 and tested various chain lengths and terminal modifications to optimize the side chain.
- - The most promising compound identified was AM8936, a nabilone analog with a C6'-cyano substitution, which showed significant potential as a CB1 agonist in laboratory and live studies, supported by docking analysis on the hCB1 receptor's crystal structure.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.ejmech.2021.114027 | DOI Listing |
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