Synthesis And Biological Evaluation Of 3-(6-(2-Fluorobenzyloxy) Naphthalen-2-YL)-2-(Cinnamamido) Propanoic Acid Derivatives

Diabetes mellitus(Diabetes Mellitus,DM) is a chronic non-communicable disease that severely impairs human health.With the change of the people's lifestyle,diabetes incidence rises year by year,and has become the most serious disease that severely impairs human health,which ranked closely behind the incidences of heart cerebrovascular disease and tumor.About 90%～95%of diabetes are non-insulin-dependent diabetes mellitus.(NIDDM,typeâ…¡diabitis).PPARα(Peroxisome Proliferators-Activated Receptorα) agonists lower the blood fats and PPARγagonists increase the insulin sensitivity.PPARα/γ,agonists possese the dual effects that lower not only the blood fats but increase the insulin sensitivity, so that they exhibit important role in the treatment of Diabetesâ…¡.Recent researches indicate that PPARγ,has the regulation effect on many kinds of tumour cell's multiplication,differentiation,and perishes,but for the anti-tumor effect it needs a further clinical tests.Protein tyrosine phosphatese 1B(PTP1B) plays a significant role in adjusting the insulin sensitivity and the fat metabolism process by dephosphorylating the insulin receptor.Consequently inhibitors for PTP1B are of therapeutic utility for treating diabetes and obesity.In the present work,we synthesized 32 3-(6-(2-flurobenzyloxy)naphthalen-2-yl) -2-(cinnamamido)proponoic acid derivatives using MCC-555,a dual PPARα/γ,agonist, as a lead compound,in which the thiazolidine diketone moiety was modified as N-substituted alanines.All structures synthesized confirmed by ¹H-NMR,MS and ¹³C-NMR.Preliminary biological evaluation for those compounds synthesized was carried in part on PPARα/γreceptor binding experiment,PTP1B inhibiting effect and anti-tumor activity,respectively.Only 10 compounds were selected to undergo the biological activity and the results showed that all tested compounds exhibited the PTP1B inhibiting effect in different extent.Meanwhile,the anti-tumor tests were also proceeded using the HeLa cell line of the human cervical carcinoma through theassay of the survival rate of HeLa cell line and 10 compounds showed significant effects on inhibiting the tumor cell growth,which considered to be further evaluated. The PPARα/γ,receptor binding tests of the compounds synthesized are in progress.