Cannabinoids. 2. Synthesis and central nervous system activities of some B-ring homocannabinoid derivatives and related lactones.
The syntheses of some novel B-ring homocannabinoid derivatives 1,2, and 4 and related lactones 3 and 5 are described. Compounds 1-5 are 6,7,8,9,10,11-hexahydrodibenz[b,d]oxepins. CNS structure-activity correlations were determined using three rodent models. The potency and activity profile of these seven-membered ring compounds were compared with the corresponding six-membered ring homologues 6 and 7. A possible seperation of CNS activities was noted with compound 1. Unexpected pharmacological activity was discovered with lactone 3, which was about equipotent to 1-delta9-tetrahydrocannabinol. It was found that dimethylation at the 7 postition decreased CNS activity when the 6 position was either a carbonyl or methylene group.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000138:chemical synthesis* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects; D003990:Dibenzoxepins / Q000138:chemical synthesis* / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology; D008745:Methylation; D051379:Mice; D013329:Structure-Activity Relationship
D002186:Cannabinoids; D003990:Dibenzoxepins; D007783:Lactones