Design, synthesis, in vitro potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties

摘要

A new series of triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds 1h-j and 1l exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10?μM, and thus were next examined in 5-dose testing mode to detect their IC50 value. The four compounds showed stronger antiproliferative activities upon comparing their results with sorafenib as a reference compound. Among them, compounds 1j and 1l possessing N-ethylpiperazinyl and N-benzylpiperazinyl terminal moiety through ethylene linker showed the greatest values of mean percentage inhibition (97.72 and 107.18%, respectively) over the 58-cell line panel at 10?μM concentration. The IC50 values of compound 1j over several cancer cell lines were in submicromolar scale (0.26?～?0.38?μM). Moreover, the compounds 1j and 1l showed highly inhibitory activities (99.17 and 97.92%) against V600E-B-RAF kinase.