Structure Modification Of An Antiobesity Drug: Rimonabant

Obesity is the most serious chronic disease of adults in the worldwide. The incidence and prevalence rates of obesity are rising year by year, many metabolic syndromes, such as heperlipidemia, atherosis, coronary disease, diabetes mellitus and so on results from obesity threaten patient's life and health directly. Therefore, To find an effective antiobesity drug which can aim at potential pathogenies and improve cardiovascular and metabolic risk factors are urgently needed. Rimonabant is the first selective cannabinoid receptor antagonist which was developed for obese therapy, having a good selectivity and affinity to cannabinoid type 1 receptor. Except markedly reduce body mass and waist circumference, it also can reduce triglycerides, cholesterol, low density lipoprotein, improve lipid, insulin resistance and many metabolic syndromes.Since rimonabant has pleiotropic functions, we designed and synthesized 23 rimonabant analogues according to its structure-activity relationships, 17 compounds had never been reported, their structures were confirmed by nulclear magnetic resonance hydrogen and carbon spectrum and mass spectrum.Take rimonabant as control experiment, 15 compounds' activity were tested in vitro, The results displayed that 4 compounds have a good activity in vitro, their inhibit concentrations to cannabinoid type 1 receptor at the same level with rimonabant.Their structure-activity relationships were analyzed so as to providing bases for better reasearch it in the next step.