Synthesis, Characterization And Biological Activities Of Triazolothiadiazole Derivatives Containing Benzimidazole And Arylsulfonyl Moities

The overexpression of Cdc25B has been linked to a variety of human cancers.Thus,Cdc25B is an attractive target for the development of anticancer therapeutics.The protein tyrosine phosphatase 1B(PTP1B)has been recognized as a therapeutic target for treatment of T2D and its adverse complications.Thus,design,synthesis and development of small molecule Cdc25B and PTP1B inhibitors have lately attracted considerable interest.1.In this paper,twenty five new 3,6-disubstituted triazolothiadiazole derivatives 7a-7y,six new intermediate compounds 3a-3b,4a-4b and 6a-6b were designed and synthesized.The structures of the target compounds and intermediate compounds were characterized by IR,1HNMR and elemental analyses.2.The intermediate compound 2 was synthesized under ultrasonic irradiation and solid-liquid phase transfer catalysis for the first time.The optimum experimental conditions were found,The experimental results indicate that this synthetic method has such advantages as short reaction time,simple operation and high yields.3.1H and 13C NMR signals of two isomers(A and B)of representative intermediate compound 4a be assigned by NMR technology,the corresponding coupling constants and the tautomeric ratios of isomers were also determined.4.The synthesized twenty five target compounds 7a-7y were evaluated for their inhibitory activities against Cdc25B and PTP1B.The structure-activity relationship(SAR)was also briefly discussed.The results show that some of them display significant inhibitory activities against Cdc25B and PTP1B.Among them,compound 7d exhibits highest inhibitory activity against Cdc25B[IC50=(7.72±0.73)?g/mL].Compound 7u exhibits highest inhibitory activity against PTP1B[IC50=(3.31 ± 0.57)?g/mL].It is noteworthy that compounds 7b,7d,71,7t and 7u exhibit higher inhibitory activities against Cdc25B and PTP1B.They can be considered as potential Cdc25B and PTP1B inhibitors,and have great application prospects in the treatment of cancers and diabetes.5.The studied results in this paper provide a scientific basis for the design,synthesis,structural characterization of new Cdc25B and PTP1B inhibitors,development of the new anticancer and anti-diabetic drugs.Therefore,this study has great significance.