The Design And Synthesis Of Gammma-Secretase Modulators As A Drug For The Treatment Of Alzheimer's Disease

Alzheimer's disease(AD)is a neurodegenerative disorder that develops in the latent with clinical symptoms of cognitive impairment and progressive loss of bodily functions and language ability and loss of the ability of daily life comprehensive dementia.With the increase of the population and the acceleration of the aging population,China and even the world's AD patients each year also will rise,to bring inconvenience to their own life and also bring a heavy economic burden to the family and society.Therefore,human society should pay more attention to Alzheimer's disease,research and development can effectively prevent,relieve and treatment of Alzheim-er's disease has become an urgent task to be solved in the present society.Causes of AD and pathogenesis of complex which bring difficulties to the treatment of AD.According to the different pathogenesis theory of AD,pharmaceutical researchers have also developed the corresponding drug targets,in order to achieve the desired therapeutic effect.At present,the role of amyloid ?-protein in the pathogenesis of AD,one of the hot spots in the research of anti-AD drugs is the action of gamma-secretase enzymes modulators.After consulting a large number of patent documents,indicated that the imidazolylphenyl group is a highly conserved pharmacophore across multiple subclasses of modulators from a number of research laboratories.So,imidazolylphenyl group as the core group can be derived from a series of new drug molecules as gamma secretase modulators.In this paper,the imidazolylphenyl group is the fixed group,design and synthesis of two benzophenone molecules as gamma secretase modulators.In the aspect of synthesis,we make use of the Grignard reagent addition reaction?oxidation and coupling reaction of a four step reactions synthesized 40 benzophenone molecules,the moleculear structure of the drug was identified by 1H NMR,13C{1H} NMR and MS,in which,all of them have not been reported in the literature,proved to be new compounds.I hope these two benzophenone drug molecules have ideal in anti-AD activity,further exploration in the following research work.