Synthesis of novel fused heterocyclic pyrazolo-pyridazine derivatives as antimicrobial agents

Abstract

A series of pyrazolo-pyridazine derivatives (4a-j) were synthesized and evaluated for their antimicrobial activities with an aim to obtain promising antimicrobial agents. In the first step, 6-substituted phenyl-2,3,4,5tetrahydropyridazin-3-one (2a,b) was prepared by reacting 4-(4-methylphenyl)-4-oxobutanoic acid (1a) and 4-(4chlorophenyl)-4-oxobutanoic acid (1b) with hydrazine hydrate. Then, aryl-aldehydes were reacted with 2 to furnish pyridazinones (3a-j). Finally, pyridazinones (3a-j) were reacted with hydrazine hydrate to furnish the title compounds (4a-j). The newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activities against six microbial strains. Compound 4i, 5-(4-Hydroxy-3-methoxyphenyl)-3-(4-chlorophenyl)3,3a,4,7-tetrahydro-2H-pyrazolo [3,4-c] pyridazine, was found to have significant action against Gram positive and Gram negative bacteria, whereas compound 4g, 3-(4-Bromophenyl)-5-(4-chlorophenyl)-3,3a,4,7-tetrahydro-2Hpyrazolo [3,4-c] pyridazine, exhibited potential antifungal activity.