Study On Synthesis Of Triazole Derivatives And Suppressed Proliferation Of K562，PANC-1Cells

Triazole as a pharmacophore present a range of biological activities,many triazolederivatives have been widely used in clinical as antifungal,antivirus, antitumor drugs.Especially,Letrozole,Anastrozole and Vorozole used successfully in clinical had themeaning of the milestone.Triazole derivatives as new and potential anticancer comp-ounds become a hot spot in the research of pharmaceutical chemistry.It is found that triazole compounds have metabolic stability and stereo selectivity.The triazole takes the place of imidazole ring with the inhibitory activity in vitro decr-eeesed and the antitumor activity in vivo increased.The desired benzotriazolylprop-2-enenitriles were designed by applying the principles of bioisosterism and combinatonwith Axitinib as a leading compound.Triazole replaces imidazole ring of Axitinib andis connected with another pharmacophore (pyridine) by C=C. Moreover, triazole isalso connected with tetrazole by–CH2–.The main work of this paper:1.Synthesis of the intermediates1.1.5-Trifluoromethyl benzotriazole was synthesized with o-diaminobenzene andNaNO2in the glacial acetic acid.1.2.Ten precursors were synthesized from the reaction of benzotriazole,5-chlorobenzotriazole,5-trifluoromethyl benzotriazole, or5,6-dimethylbenzotriazoleand chloroacetonitrile in the acid binging agent [KCO3/ethyl acetate], respectively.Eight of them are new precursors.2.Synthesis of the desired comnpounds2.1.Twelve novel desired benzotriazolylprop-2-enenitriles were synthesized from thereaction of M1, M2, F1, F2or F3with pyridine-2-aldehyde, pyridine-3-aldehyde, orpyridine-4-aldehyde, respectively. 2.2Seven desired benzotriazole derivatives were synthesized from the reaction ofB1, B2,2M1,2M2, C1, C2or C3with NaN3under microwave irradiation in toluene,respectively.All the intermediates and target compounds were characterized by IR and1H-NMR.3.The antitumor activity of nineteen novel benzotriazolylprop-2-enenitriles wasdetermined by MTT assay. The results showed that benzotriazole derivativessuppressed proliferation of K562and PANC-1cells in a dose-dependent manner. Theinhibiting rate of2M2P2on K562and PANC-1cells was the highest with IC500.046μg\mL and0.06μg\mL, respectively.