Stereochemical requirements for cannabimimetic activity.
The SAR of cannabimimetic activity in the cannabinoid series are reviewed with emphasis on the stereochemical requirements. Some new results are presented. The most important are that a, in humans, (-)-(1S)-delta-3-THC is much more active than (+)-(1R)-delta-3-THC; and b, with the 7-OH-delta-6-THC DMH enantiomers (32) and (33), the activity in several animal species resides completely in the (-)-(3R, 4R) enantiomer (32), the difference between the two enantiomers being up to several thousand times. The (3R,4R)-enantiomer (32) is much more active than delta-1- or delta-6-THC in animal tests, the exact level of activity depending on the test employed. The cannabimimetically inactive (+)-(3S,4S) enantiomer (33) was shown to be a potent analgetic in several animal tests. Thus, a complete dissociation between the cannabimimetic and the analgetic effects in a cannabinoid has been achieved, apparently for the first time.
D000700:Analgesics; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D002186:Cannabinoids