| Diabetes Mellitus is a common, chronic, long-term disease, which serious threat against human health. Type 2 diabetes (noninsulin-dependent diabetes mellitus, NIDDM) accounts for 90%-95% of diabetes cases world-wide, Most diabetic patients have an abnormal lipid profile, Type2 diabetes is mainly due to insulin resistance. Peroxisome Proliferator - Activated Receptor γ agonists are insulin sensitizers, however, it accompanning with the patients' weight gain. PPARa agonists are the lipid-loweringdrugs, dual-acting PPARα/γ agonists have been reported to improve insulin sensitivity and reduce lipid in patients. Therefore, It's significant for the treatment of type 2 diabetes.On the basis of the structure of PPARα/γ receptor and the complex with GW409544, The program Dock was used to simulate the interaction between compounds and ligand binding domain, a dual-acting agonist, a set of compounds with the structure of L-tyrosine and its substitude by bromine , 2-Acetylamino-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid derivatives, was designed.In this study, 23 of two sets of compounds were synthesized, All of their structures were identified by ~1H-NMR, MS. The results of activity test showed that the activity on PPARα/γ of compund L140H, L132H are comparable to GW409544. |
