Study On Synthesis And Antitumor Activities Of Substituted Benzotriazole Derivatives

Benzotriazole derivative is an important class of fused-ring. The listed tyrosine kinase inhibitor achievement has the meaning of landmark in clinical.Benzotriazole derivatives have attracted considerable attention due to their widespread biological activities.These compounds have good results in the cure of cancer, virus, fungus. The desired benzotriazolylprop-2-enenitriles were designed by applying the principles of bioisosterism and combination. With Axitinib as a leading compound, benzotriazole ring replaces indazole ring of Axitinib and is connected with another pharmacophore by C=C. In this paper, it is discussed the influence of introducing electron-withdrawing or electron-donating group into the benzene ring of benzotriazole on the yield and antitumor activity of title products. The main work of this paper:1. Five new precursors were synthesized with 5-chlorobenzotriazole or 5-methylbenzotriazole and chloroacetonitrile in the acid binging agent [K2CO3/ethyl acetate]. The products were characterized by IR and 1H-NMR.2. Fifteen novel desired benzotriazolylprop-2-enenitriles were synthesized with pyridine-2-aldehyde, pyridine-3-aldehyde, pyridine-4-aldehyde respectively. The structures of the target compounds were characterized by IR and 1H-NMR. 3. The antitumor activity of fifteen novel benzotriazolylprop-2-enenitriles was determined by MTT assay. The results showed that benzotriazole derivatives suppressed proliferation of K562,SW1990 cells in a dose-dependent manner. The inhibiting rate of(C2P2) on K562,SW1990 cell was the highest with IC50 0.95μg/mL,0.46μg/mL which could be used as research emphasis to further development of this kind compounds.