1H‐Pyrazole‐Appended Pyridines and Their 1,2,4‐Triazine Precursors: A Rational Synthesis and in silico and in vitro Evaluation of Anti‐Cancer Activity.

An operationally facile and high yielding one‐pot protocol has been developed for the preparation of pyridines appended with pyrazole via NH linker. This protocol includes SNipso/aza‐Diels‐Alder reactions in up to 54 % yields starting from 1,2,4‐triazine precursors. All the synthesized compounds have been evaluated for their in silico activity against JAK1, SYK, and FAK1 kinases. The most promising compound was tested in vitro using A‐172, Hs578T, and HepG2 cancer cell lines and exhibited considerable cytotoxicity with IC50 values <50 μM in A‐172 and HepG2 cell lines. Anticancer in vitro activity correlates well with the predicted in silico data. [ABSTRACT FROM AUTHOR]