Synthesis, Crystal Structure And Bioactivity Of Noval Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives

Research indicates that the cell division cycle25phosphatase B (Cdc25B) areover-expressed in various primary human cancers including breast, colon, cervix, lung, etc.This suggests that the inhibition of Cdc25B may become a promising strategy in oncology.Therefore, it is great significant to synthesize of novel imidazole[2,1-b][1,3,4]thiadiazolederivatives which have brilliant biologically active.In this paper, intermediate3,2-aryl-5-amino-1,3,4-thiadiazoles, have been synthesizedby nitrochlorobenzene and p-cresol as original materials via multi-step reaction. Then, twentynovel2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazoles4have been synthesized by the reaction ofintermediate compounds3and (un)substituted-bromoaryl ketones in DMF undermicrowave irradiation. Finally, nineteen novel2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes5have obtained byVilsmeier-Haack reaction. The structures of new compounds3,4and5were characterized byIR,1H NMR spectra and elemental analysis. The crystal stucture of target compund4s wasanalysed by the X-ray diffraction.The bioactivity of synthesized target compunds4and5were evaluated as Cdc25Binhibitors and β-2AR agonists. Result of the studies revealed that all target compound showedinhibility of Cdc25B, while none of them showed protential capability as β-2AR agonists.And compound4c showed highest inhibitory activity against Cdc25B with percentageinhibition87.68%at5μg/mL, compounds4o and5c showed moderate activities withpercentage inhibition55.76%and57.69%, respectively. They can be considered as potentialcandidates as novel Cdc25B inhibitors.