Novel series of cannabinoid modulators for thetreatment of obesity associated disorders

PETROV, R.R.; ASTRUC-DIAZ, FANNY; CAVASOTTO, CLAUDIO N.; DIAZ, PHILIPPE

Anaheim, CA

Conferencia; 241st Meeting of the American Chemical Society; 2011

With more than 1 billion overweight adults worldwide, obesity continues to be an escalating threat to global human health. Circulating levels of the endocannabinoids acting on cannabinoid receptors CB1 and CB2 are elevated in obese individuals. A suitable strategy to reduce overactivation by endocannabinoids is to use compounds which antagonize corresponding binding and activation mechanisms. We aimed to further develop and optimize compoundsantagonizing both CB1 and CB2 mediated activations by endocannabinoids as a novel and effective therapeutic approach for treatment of obesity associated disorders. Two series of novel canabinoid modulators based on two heterocyclic scaffolds, have been synthesized. Highly potent dual modulators for CB1 and CB2 were identified in both series. Selected compounds have been tested on in vivo relevant models with CB1 and CB2 activities. Details about the synthesis, CB1 and CB2 receptors in vitro data, resulting SAR, molecular modeling and in vivo activities will be presented.