Design And Synthesis Of The No Donor Non-imidazole H₃ Receptor Antagonists

In recent years, some central nervous system diseases (such as Alzheimer's disease (Alzheimer's Disease, AD), Parkinson's disease), the Morbidity has increased year by year. Histamine H₃ receptor is Inhibitory of its own receptor and also is the Inhibitory of heterogeneous receptor. In the central nervous system and peripheral nervous system are widely distributed.Studies in recent years have shown that, histamine (H₃) receptors as the target could design many H₃ receptor antagonist. These antagonists display a very good prospect in the future's clinic. Such as in the treatment of Alzheimer's disease (Alzheimer's Disease, AD), Parkinson's disease, and other central nervous system diseases.Through analyzed the the existing H₃ receptor antagonists'QSAR, we found that many non-imidazole H₃ receptor antagonist have the alkylamine-propoxy-phenyl group. This pharmaceutical is proved to be a very effective structure for the H₃ receptor antagonist, also in view of coupling with the NO donor for such H₃ receptor antagonist show good H₃ receptor antagonist activity, Finally, Through using many drug design methods such as electronic row, pieced together in principle, we design a series of target compounds which not only coupled with the nitric oxide (Furazan nitrogen oxides) donor but also contained the tetrahydropyridine ring . In addition The alkylamine-propoxy-phenyl pharmaceutical is a Notable features of these target compounds.In the course of the experiments we through used 3-chloropropanol and other raw materials, after Implementation nuclear replacement, Oxidation, reduction reaction could get a Candidate target compound.3 - methyl -4- chloromethyl -1,2,5 - oxadiazole -2– oxides and 3 - methyl -4- bromomethyl -1,2,5 - oxadiazole -2– oxides are two important nitric oxide donor. Reported in the literature displayed the complex process of synthetic route, also the low yield. In the experiment we through use the crotonaldehyde as a starting material, after the addition and Cyclization of the material get the 3 - methyl-4– furancarboxaaldehyde.under reduction stage we use the polar-Proton solvent ethanol instead of the polar-nonProton solvent dioxane in the literature. this step didn't need further purified,can directly chlorinated and brominated immediately. In this process NBS was Instead of thionyl bromide as a Bromide reagents. At last the target compound yield had been successfully increased a lot, also simplified the process of the operation and speeded up the research, What we have done is a very good foundation for the future reserch in this field.