Synthesis And Characterization Of Dipeptidyl Peptidase-â…£ Inhibitor Sitagliptin And Its Analouges

Nowadays, diabetes is a global clinical and public health problem, nearly 90% of the diabetes was diagnosed as Type 2 diabetes(T2DM). T2DM is a metabolic disease characterized by insulin resistance, hyperglycemia and hyperlipidemia. Dipeptidyl peptidase-â…£(DPP-â…£) is a new target to treating T2DM, plays a crucial role in immune system, nervous system and endocrine system. It can control T2DM from upper reaches by inhibit DPP-â…£activity.Sitagliptin is the first DPP-â…£inhibitor drug on the market approved by the U.S. Food and Drug Administration (FDA), it is used for the treatment of T2DM. The prupose of this research is to improve and optimize the synthetic routes of Sitagliptin, design and synthesis novel Sitagliptin analogues.The main content as follows:The pathogenesis and main treatment drugs of diabetes, DPP-â…£inhibitor mechanism and the status quo, the clinical research findings of Sitagliptin are reviewed in chapter one.The synthetic route of sitagliptin was designed on the basic of analysis the existing synthetic routes, sitagliptin was successfully synthesized in chapter two.Four novel Sitagliptin analouges was designed and synthesized in chapter three, they and their key intermediates structure were characterized by ¹H NMR, ¹³C NMR, IR, MS. The four compounds are separately: 7-(3-amino-3-phenylpropanoyl)-3-trifluoromethyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]piperazine(SA-1); 7-(3-amino -3-(4-methoxyphenyl)propanoyl)-3-trifluoromethyl-5,6,7,8-tetrahydro[1,2,4]triazolo [4,3-a]piperazine(SA-2); 7-(3-amino-3-(2-chlorophenyl)propanoyl)-3-trifluorometh -yl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]piperazine(SA-3); 7-(3-amino-3-(2-chlorophenyl)propanoyl)-3-trifluoromethyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] piperazine(SA-4).