Synthesis And Analysis Of Two Series Of Pharmaceuticals For Treatment Of Diabetes Ⅱ

Diabetes is a chronic disease which is very harmful to people′s health and the third death factor inferior to cardiovascular disease and tumor. Some new anti-diabetic drugs were invented with high efficiency and obvious toxicity by chemists and pharmacists. In this thesis, we summarize the relation of diabetes and insulin resistance. With the increased understanding of the precise mechanisms of TZD (thiazolidinedione) class of insulin sensitizer, PPARγ(Peroxisome Proliferator -Activated Receptorγ) has also been identified as the major functional receptor for the drugs. In the study of the relationship between PPAR and insulin resistance, considerable gaps appeared. TZD induced activation of PPARγis known to promote insulin sensitivity. More interestingly, however, PPARγ+ / - heterozygous mice were shown to be less susceptible to insulin resistance. These findings suggest that the relationship between PPAR activation and insulin sensitivity improvement is not simply positively related. A better understanding of the role of PPAR in insulin action system will be critical in developing more efficacious and safe agent s that act on PPAR and benefit patients with type 2 diabetes. The main content is followed: Synthesis and analysis of 1,3-dicarbonyl compounds. Make use of easily available cheap reagent such as 2-naphthol, 6-hydroxyquinoline, 1,2-dibromoethane, 4- hydroxybenzaldehyde, dimethyl malonate, 2-{4- [(2-napthoxy)ethoxyl] benzyl} malonates and 2- {4 [(1,2,3,4-tetrahydro-6 -quinolinoxy)ethoxyl] benzyl } malonates were synthesized through 6-8 steps in virtue of Williamson, Knoevenagel reaction, Pd/C catalyzed hydrogenation with mild conditions and high yield. The total yield of 40-50%.Through biological screening, it is found that PPARα activities are 2.1-2.6 higher than Wy- 14643,but PPARγ activities are only 70-80%of roglitazone .Synthesis and analysis of l-tyrosine derivatives substituted with three-ring group. Through dehydration reaction, phase transfer catalysis, esterification and hydrolysis, 2-[2-(carbomethoxy)anmobenzyl]-3-{4-[2-(N-carbazyl)ethoxyl] benzyl } malonates were synthesized through 6 steps with total yield of 12-18% employing the easily available cheap reagent such as L-tyrosine ester,Ethyl cyclohexanone- 2carboxylate, carbazole, 1,2-dibromoethane.Target molecules are analysis by UV, NMR, IR and MS. Through biological screening, it is found that PPARγ activities are 1.2-2.1higher than roglitazone .