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.