Synthesis and pharmacological properties of 11-hydroxy-3-(1',1'-dimethylheptyl)hexahydrocannabinol: a high-affinity cannabinoid agonist.
11-Hydroxy-3-(1',1'-dimethylheptyl)hexahydrocannabinol (1) was synthesized from the known cannabimimetic analog (+/-)-nabilone. Racemic 1 was resolved by HPLC on a semipreparative CHIRALCEL OD column (Daicel, Inc.), and pharmacological activities of the individual enantiomers were evaluated in the mouse model. The (-)-enantiomer was found to be much more potent than the (+)-enantiomer in all the four measures with the potency ratios in the production of catalepsy (RI), hypoactivity (SA), hypothermia (RT), and antinociception (TF) being 93, 143, 186, and 322, respectively. The racemic 11 alpha-OH diastereomer (2), a reaction side product, was also evaluated in the mouse model. Only small differences in the pharmacological activity of racemic 1 and 2 were found in the above four measures.
Yan
G
G
Section of Medicinal Chemistry and Pharmacognosy, School of Pharmacy, University of Connecticut, Storrs 06269.
Yin
D
D
Khanolkar
A D
AD
Compton
D R
DR
Martin
B R
BR
Makriyannis
A
A
D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002186:Cannabinoids / Q000737:chemistry* / Q000494:pharmacology; D002187:Cannabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D013759:Dronabinol / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002186:Cannabinoids; C088811:11-hydroxy-3-(1',1'-dimethylheptyl)hexahydrocannabinol; C011941:nabilone; D013759:Dronabinol; D002187:Cannabinol