Exploring the substituent effects on a novel series of C1'-dimethyl-aryl Delta super(8)-tetrahydrocannabinol analogs

The synthesis and characterization of novel C1'-phenyl-substituted Delta super(8)-THC analogs were previously reported by our laboratory. Within this small series of compounds, the C1'-dimethyl phenyl group was found to impart 13.5-fold selectivity for the CB2 receptor with a K sub(i) 0.91...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-07, Vol.16 (13), p.6489-6500
Main Authors: Krishnamurthy, Mathangi, Gurley, Steven, Moore, Bob M
Format: Article
Language:English
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Summary:The synthesis and characterization of novel C1'-phenyl-substituted Delta super(8)-THC analogs were previously reported by our laboratory. Within this small series of compounds, the C1'-dimethyl phenyl group was found to impart 13.5-fold selectivity for the CB2 receptor with a K sub(i) 0.91 nM. The current study expands on the previous report by evaluating the effects of aromatic ring substitution on CB1 and CB2 receptor subtype binding and selectivity. The ring substituents synthesized in this study include aliphatic, halogen, nitrile, and acetamido functional groups. In addition, the isosteric replacement of the phenyl group by thiophene was evaluated. The anti-glioma activities of selected compounds were evaluated in vitro and compared to the lead compound 2.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2008.05.034