An efficient synthesis of hitherto unreported 3-heteroaryl-pyrroles was described via regioselective 1,3-dipolar cycloaddition reactions of enaminone2 or 3 with nitrilimines 5a–j to afford the corresponding pyrazole derivatives 7a–j. Hydrazinolysis of 7a–f yielded the respective pyrazolo[3,4-d]pyridazines 10a–f. Furthermore, pyrrole analogs substituted on the 3-position with pyranone (14), benzofuran (16) or naphthofuran (18) were also synthesized. The structures of the synthesized compounds were determined by spectral, elemental analyses and alternative syntheses wherever possible. The synthesized compounds were evaluated for their protein kinase inhibitory activities against 25 kinases belonging to 4 kinase groups viz. AGC (5 kinases), CAMK (5 kinases), CMGC (4 kinases) and TK (11 kinases). While the tested compounds were found to be good inhibitors of VEGFR-2 and EGFR, exhibiting low micromolar IC50 values, they were selectively more potent against CHK1 eliciting a potent inhibitory effect with IC50 values in the submicromolar range. Finally, docking studies were performed to interpret the possible binding mode of the target compounds with CHK1.
