Abstract:

Eighteen novel molecules(4a~4i and 5a~5i) containing 1,2,4-triazole [3,4-b]-1,3,4-thiadiazol and 1,3,5-triazine connected by benzoamino bridge were synthesized. The structures of target molecules were characterized by infrared spectroscopy(IR), nucleic magnetic resonance spectrometry(NMR) and high resolution mass spectrometry(HRMS). Compounds 1A(2,6-dimorpholino-4-chloro-1,3,5-triazin) and 1B(2,6-dipyrrolidin-4-chloro-1,3,5-triazin) were synthesized by the reaction of cyanuric chloride with morpholine or tetrahydropyrrole respectively. The important intermediates 2A and 2B were then afforded by the reaction 1A and 1B with p-aminobenzoic acid respectively. Compounds 3a~3h were obtained by the condensation reaction of eight kinds of aliphatic acids with thiocarbohydrazide using melting method. The target molecules were finally afforded by the reaction of 2A and 2B with 3a~3h respectively under the catalysis of phosphorus oxychloride and tetrabutyl ammonium bromide. In order to compare the effect of 3-aliphatic and 3-benzyl on the bioactivity, 4i and 5i were synthesized according to the same method. The inhibitory activities against cell division cycle 25B(Cdc25B) and protein tyrosine phosphatase 1B(PTP1B) of the target molecules were evaluated. The results show that all of the target molecules have good inhibition against Cdc25B, the values of half inhibition concentration(IC₅₀) are 2.40~0.31 mg/L, the values of IC₅₀ of the target molecules 4a~4f and 5a~5i are lower than contrast reference trisodium vanadate((1.25±0.14) mg/L), they are expected to be the potential inhibitors against Cdc25B; In the test of PTP1B, fourteen target molecules have good inhibitory activity, the values of IC₅₀ are 0.98~0.37 mg/L, which are lower than that of contrast reference oleanolic acid((1.19±0.27) mg/L), and they are expected to be the potential inhibitors against PTP1B.

Key words: triazole [3,4-b]-1,3,4-thiadiazol, triazine, cell division cycle 25B, protein tyrosine phosphatase 1B