Studies On The Design, Synthesis Of CB1 Receptor Antagonists

Obesity is a kind of normal illness in modern society. Medication mostly aimed at increasing the energy waste of body and curing it in the past. Recently, scientists have found a receptor which has close relationship with human's appetite-central cannabinoid receptor type1 (cannabinoidl, CB1), and have approved that its antagonists could bind with the receptor highly affinitively and selectively, then could restrain the rodents' appetite precisely and lastingly. Periodic usage could continue to relieve the weight. Furthermore, by the side of treating central nerve system disease, the antagonists of CB1 receptor show good activity too.Because the antagonists of CB1 receptor have different and effective activities, we summarized the structure-activity relationship (SAR) of the antagonist about the type of 4-methyl-1H-diaryl-pyrazole, designed and synthesized a series of CB1 antagonists cored about 4-methyl-1H-diaryl-pyrazole, combining CoMFA with chemical modification. All of them were confirmed by ~1H-NMR, MS.In this study, 20 compounds were synthesized, 14 of which had never been reported. The bioassay of the compounds against CB1 receptor in vitro, and the cell culturassay of anti-obesity have been done. The results of activity test showed that the CB1 antagonist activities of MJ01, MJ15 were comparable to SR141716. Metabolism characters of all compounds were predicted by VolSurf.The structure-activity relationships of the compounds mentioned in this text have been discussed, which make theoretical and practical bases for future work on the project searching for more potential CB1 antagonists.