Synthesis And Biological Activity Of 6-methyl-7-substituted Tetrazolo[5, 1-c] [1, 2, 4] Triazin Derivatives

Objective Purine nucleoside analogues are anti-metabolic anticancer drugs,which are attended widely in recent years. By portion atoms or groups of the purine bases are displaced to change the structure of the base required for the biosynthesis of nucleic acid, thus,the survive of tumor cells are suppressed. In this subject, applying bioisoterism, wedesigned and synthesized a series of purine base analogues, expecting to find lead compounds that have the high bioavailability and low toxic side effect of anti-cancer effects by screening them.Methods Firstly, 6-methyl-3-Mercapto-[1, 2, 4]triazin-5-ol(intermediate 1) was synthesized from thiosemicarbazide and pyruvate. 6-Methyl-tetrazolo[5, 1-c][1, 2, 4]triazin-7-ol(intermediate 2) was synthesized by hydrazinolysis and diazotization off ring from intermediate 1. Secondly, 6-methyl-7-Chloro-tetrazolo[5, 1-c][1, 2, 4]triazin(intermediate 3)was synthesized by chlorination from intermediate 2. Finally, 6-methyl-7-substituted tetrazolo[5, 1-c][1, 2, 4]triazin derivatives were synthesized by intermediate 3 and series of amines. The structures of these compounds were identified by the methods of1H-NMR,13C-NMR, LC-MS, IR, etc. All compounds were rushed to Shanghai Institute of Materia Medical Chinese Academy of Sciences for Screening pharmacological activity. Results Three intermediates and twelve new target compounds were synthesized and four of the compounds had some effect on cell division cycle 25 homolog B(CDC25B). Conclusion The resulting compounds were all confirmed to be the objective compounds by spectroscopic methods. It was found that the inhibition rates(% inhibition) of the CDC25 B were 50.21,64.59, 50.23 and 50.26 by compounds 3, 4d, 4f and 4g with a certain biological activity.Subsequent pharmacological experiments are under way.