The Conformational Properties of the Highly Selective Cannabinoid

During a search for novel drugs possessing analgesic properties but devoid of the psychotropic effects of mar-ijuana, a group of molecules designated as nonclassical cannabinoids was synthesized by Pfizer. Of these non-classical cannabinoids CP-55,940 has received the most attention principally because it was used as the high affinity radioligand during the discovery and character-ization of the G-protein-coupled cannabinoid receptor. In an effort to obtain information on the stereoelec-tronic requirements at the cannabinoid receptor active site, we have studied the conformational properties of CP-55,940 using a combination of solution NMR and computer modeling methods. Our data show that for the most energetically favored conformation, (i) the aro-matic phenol ring is perpendicular to the cyclohexan