Optimized Preparation Process Bulk Drugs Hpn And PTP1B Inhibitors And New Design, Synthesis And Biological Activity Study

Protein tyrosine phosphatase 1B (PTPIB), as negative regulatory factors of insulin signal transduction, which have been identified as drug targets of treating type-II diabetes and obesity. The bromine phenols compound 3-bromo-4-[(2,3-dibromo-4, 5-dihydroxyphenyl)-methyl]-5-[(ethoxy)-methyl]-1,2-hydroquinone (BPN) are seprated from Rhodomela confervoides. It has the highest inhibitory activity, which the value of IC50 has reached 0.84μmol/L. Raw material drugs of 3,4-dibromo-5-[(2-bromo-3,4-dihydroxy-6-isopropoxy methyl-phenyl)-methyl]-1,2-benzene diol (HPN) is bromine phenols compounds that possess higher inhibitory activity, which is synthesized on the basis of the BPN (structure modification) in the laboratory, its value of IC50 reached 0.63μmol/L. Furthermore, HPN exhibits effective anti-hyperglycemia activity in db/db T2DM mouse model.Because of the yield of following the original synthesis process route of raw material drugs HPN is very low, only 12%. If you want to numerous produce HPN, it has to optimize the original process route to advance the yield. The paper optimized the synthesis process on the basics of original synthesis of raw material drugs HPN. Through different reaction condition and treatment method,we enhanced the toeal yield of HPN 20%,its purity reached over 95%.In this paper, we modified the isopropoxy structure of HPN to other structure, and expect for higher PTPIB inhibitory activity compound. After modification, we got four major categories compounds, thiazole ring TZDs; oxalate single lipid; succinic anhydride; amino classes. And determined these compounds were determined in vitro activity.