MEDI 30 |
| Cannabinoid receptor agonists, such as CP55,940 and WIN 55,212-2, produce potent antinociception with equivalent efficacy to morphine in animal models of pain. They also induce a number of unwanted CNS side effects, which are accounted for by the central distribution pattern of CB1 receptors. Catalepsy in mice is indicative of CB1 activation and predictive of cannabinoid psychoactivity. A separation between therapeutic effects and undesirable CNS side effects could be accomplished by preventing the cannabinoid from crossing the blood brain barrier. We report here that it is possible to peripheralize CB ligands, using a unique combination of polar substituents on a cannabinomimetic biaryl core, retaining the binding affinity to the receptors but preventing CNS side effects from occurring as demonstrated by the absence of catalepsy in the ring test at doses up to 100 mg/kg i.p.. Synthesis, SAR and initial biological evaluation in animal models of pain will be presented. |
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |