Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAFV600E inhibitors

A series of novel 5-phenyl-1H-pyrazole derivatives were designed and synthesized. Among which 2-fluoro-N-(5-(p-tolyl)-1H-pyrazol-3-yl)nicotinamide (5h) exhibited the most potent inhibitory activity with an IC50 value of 0.33 μM for BRAFV600E, 2.63 μM for WM266.4 cells and 3.16 μM for A375. Docking simulation was performed to insert compound 5h into the crystal structure of BRAFV600E at SB-590885 binding site to determine the probable binding model. These results suggested that compound 5h may be a promising antitumor agent for the potential treatment of cancer.