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.