Selective and potent analgetics derived from cannabinoids.
Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (--)-9-nor-9 beta-hydroxyhexahydrocannabinol (HHC). A new grouping, the 1-methyl-4-phenylbutyloxy C-3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C-5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.
D000700:Analgesics; D000818:Animals; D002186:Cannabinoids / Q000138:chemical synthesis / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology; D051379:Mice; D010616:Phenanthrenes / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D002186:Cannabinoids; D010616:Phenanthrenes; D010617:Phenanthridines; D010636:Phenols; D013759:Dronabinol