Design,Synthesis And Bioactivity Investigation Of Novel Benzothiazole Derivatives As The Novel SR-B? Expression Up-regulators

Cardiovascular disease(CVD)is a circulatory system disease characterized by high prevalence,high morbidity,high mortality,high recurrence rate and multiple complications.In both developed and developing countries,CVD has become the leading cause of disease mortality.Prevention and treatment of CVD is an urgent matter.Atherosclerosis(AS)is the main cause of CVD,and lipid metabolism disorder is an important risk factor for AS.A large number of studies have shown that the incidence of AS is closely related to the level of high-density lipoprotein cholesterol(HDL-C),that is,the lower the incidence of AS would be when the higher the level of HDL-C is.HDL promotes the protection of blood vessels by promoting cholesterol reverse transport(RCT).Among them,type B type I scavenger receptor(SR-B?)which is the only confirmed receptor of HDL is an important protein in RCT process.SR-B ?overexpression can significantly improve HDL level,promote the outflow of intracellular cholesterol,and effectively prevent and reduce AS formation.Therefore,the research on the up-regulation of SR-B expression has been widely concerned,?and it has become a new idea for the development of new and more effective anti-AS drugs.In this paper,based on the principle of electron,the novel SR-B expression ?up-regulators were designed using compound 5242331 as the lead.The substituents of the benzothiazole ring and amino groups were investigated.Starting with aniline,18 novel benzothiazole derivatives were sequentially obtained via addition,cyclization,sulfonylation,reduction and substitution et al.The structure was confirmed by 1H-NMR,13C-NMR and MS.Cell model was used to investigate the up-regulated expression activity of the target compounds on human SR-B?.The results showed that the compound had only a weak up-regulated expression activity and the reasons for the poor activity of the compounds was analyzed.In addition,another key proteins in the RCT cycle,ATP rise in combination box transporter A1(ABCA1)expression activity also were tested?The results showed that benzothiazole compounds 5-1,5-10 and 5-15 have well up-regulation activity with the EC50 values 2.51 ?mol·L-1,2.57 ?mol·L-1,3.71 ?mol·L-1 respectively.The structure-activity relationship was summarized.This kind of compound has some further research value for the expression of ABCA1.SR-B is a new hot spot for anti?-AS,which is widely concerned by researchers.In this paper,based on the principle of electron,the novel SR-B ?expression up-regulators were designed using compound 5242331 as the lead,and the up-regulation activity of SR-B expression? were evaluated,while their activities were not good.In addition,the up-regulated expression activity of another key protein ABCA1 in the RCT cycle was also tested,and the preliminary structure-activity relationship was analyzed through the test results.The compound in this paper has laid a foundation for further design of SR-B ?expression with novel structure and low toxicity.