Study On Synthesis And Optimization Of Rimonabant's Synthetic Route And Its Me-too Reseach And Development

The endocannabinoid is a neurotransmitter molecule. It can lead to increase appetite and diet through specifically binding with the cannbinoid one(CB1) receptor,and it is an important reason of diet-induced obesity. Inhibiting CB1 receptor can effectively reduce the body's intake of food and increase energy consumption. So CB1 receptor is a new target of treatment of obesity. With the development of the drug of Rimonabant, CB1 receptor inhibitor becomes a hot field in the reseach and development of anti-obesity drug. In this paper, the mechanism, reseach and development of CB1 receptor inhibitor were summarized. Synthetic route of Rimonabant was studied and optimized. A new series of Rimonabant's derivatives were designed and synthesized. The CB1 receptor affinities of these new compounds were tested.The main contents and conclusions of this paper are discussed as follows:The synthetic route of Rimonabant was got through and optimized by a new synthesis method of 4-(4-Chloro-phenyl)-3-methyl-2,4-dioxo-butyric acid ethylester and the improvement of other reactions. Finally,the price of Rimonabant is substantially lowered and the synthetic route is more suitable for industrial production.About 14 of Rimonabant's derivatives were designed and synthesized according to structure-activity relationship study. The structures of new compounds were confirmed by mass spectrum,nulclear magnetic resonance hydrogen and carbon spectrum.The CB1 receptor affinities of these new compounds were tested. And the next step of the study was determined through the discussions of the screening results.