Synthesis, Reactions, and Pharmacological Evaluations of Some Novel Pyridazolopyridiazine Candidates

Herein, we report the synthesis, characterization, and preliminary pharmacological activity of a new series of substituted pyrazolopyridazine derivatives. Compound 1 was reacted with ethoxymethylene malononitrile 2 in refluxing ethanol to give the corresponding compound 3, which was treated with hydrazine hydrate or formamide to give pyrazolo[3,4-c]pyrazole 4 and pyrazolo pyrimidine 5 derivatives, respectively. Also, compound 3 was reacted with NH4SCN or carbon disulphide or ethyl acetoacetate to yield the corresponding pyrazolo derivatives 6, 7, 8, respectively. Additionally, compound 3 was reacted with triethyl orthoformat in acetic anhydride to give 9, which was treated with hydrazine hydrate to give hydrazino derivative 10. The latter compound transformed into the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]-pyrimidine 11 via refluxing with acetic anhydride. Finally, compound 9 was reacted with benzoic acid hydrazide or mercapto acetic acid to give compounds 12 and 13, respectively. The latter compound was treated with refluxing ethanolic sodium ethoxide solution to afford the pyrazolothiazolopyrimidine 14. Some of the compounds exhibited better activities as anti-inflammatory and antimicrobial agents than the reference controls. The detailed synthesis, spectroscopic data, anti-inflammatory, and antimicrobial activities of the synthesized compounds was reported.