Abstract
In this study, [4-(N-substituted sulfamoyl)phenyl]carbonohydrazonoyl dicyanides 3a-c were synthesized and condensed with various hydrazine hydrate derivatives to produce the corresponding 3,5-diaminopyrazole derivatives 4-9, respectively. Furthermore, condensation of 3b with alpha-naphthol, urea and thiourea yielded the pyrimidine derivatives 10 and 11a,b, respectively. Also, condensation of 3b with hydroxylamine hydrochloride produced the isoxazole derivative 12. Treatment of 3b with different secondary amines afforded the piperidine and piperazine derivatives 13a-c, respectively, while its condensation with diamines yielded the corresponding diazepine, benzodiazepine and benzooxazepine derivatives 14-16. Reaction of 3b with malononitrile or diazonium salt 2b with MND followed by treatment with malononitrile afforded the pyrido-pyridazine derivative 18. Anti-inflammatory and analgesic evaluation of some of the synthesized compounds as representative examples exhibited equipotent activity to that of the reference drug celecoxib. The ulcerogenic potential of the tested derivatives showed a complete safety profile on G.I.T. system. Molecular docking studies showed that the tested compounds induced good fitting and forming different hydrogen bonds with the amino acid residues at the active sites of COX-2 enzyme.