Synthesis Of Phosphorous And Phosphate Class Which Substituted With Pyridine Or Pyridine[3,2-h]quinazoline

This thesis consists of three chapters, and focused on the design and synthesis ofphosphorous and phosphate class which substituted with pyridine orpyridine[3,2-h]quinazoline. The first chaper summarized the current status of FBPaseand the derivatives of AMP as a FBPase inhibitor.Type2diabetes mellitus is a metabolic disorder of epidemic proportions that ischaracterized by insulin resistance, relative insulin insufficiency, and increasedendogenous glucose production (EGP). These abnormalities underlie the highcirculating glucose levels (hyperglycemia) associated with the disease. The majorityof current antidiabetic drugs reduce glucose levels by improving peripheral insulinresistance and/or augmenting insulin secretion. The liver is the main organ responsiblefor EGP. Glucose is produced by the liver by two pathways: gluconeogenesis andglycogenolysis. Phosphoenolpyruvate carboxykinase (PEPCK),fructose-1,6-bisphosphatase (FBPase),and glucose-6-phosphatase (G-6-Pase), these threeenzymes form the major control points in gluconeogenesis have all been targets of drugdiscovery efforts. AMP increases intracellular ATP levels in large part by regulating fluxthrough pathways governing carbohydrate and lipid biosynthesis and metabolism.AMP acts by directly or indirectly modulating the activity of the key rate controllingenzymes in these pathways. Catalytic activity is typically affected through the bindingof AMP to allosteric sites, which may therefore represent potential drug targets formetabolic diseases such as diabetes and so on. AMP binds to FBPase at an allostericbinding site. AMP has been researched widely as a FBPase inhibitor.In the second chapter, the synthese of phosphorous and phosphate class whichsubstituted with pyridine or pyridine[3,2-h]quinazoline derivatives were described.We recommend a carboxyl or an acyl on the pyridine for derivatization in the follow-up work. We made the5-bromopicolinic acid undergo a acidylation,phosphorylation and dephosphorylation as a starting material. Then we recieved9compounds, include3carboxylic acid and6acylamide. Phosphorous and phosphateclass substituted with pyridine[3,2-h]quinazoline had been received by3-bromoquinoline.We exchanged the furan group with pyridine or pyridine[3,2-h] quinazoline inthe FBPase inhibitor has been researched by professor Qun Dang and his group tofilter more FBPase inhibitors with high OBAV(oral bioavailability).