Exploring the substituent effects on a novel series of C1'-dimethyl-aryl Delta8-tetrahydrocannabinol analogs.
The synthesis and characterization of novel C1'-phenyl-substituted Delta(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(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.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee-Memphis, 847 Monroe Avenue, Room 327D, Memphis, TN 38163, USA.
Mathangi
M
Krishnamurthy
Steven
S
Gurley
Bob M
BM
Moore
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005910:Glioma / Q000473:pathology; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D013329:Structure-Activity Relationship
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol