Convenient Synthesis of Some Novel Pyridazinone-Bearing Triazole Moieties

Abstract

The chemoselective reactions of 2-(5-mercapto-4-phenyl-4H-[1,2,4]triazol-3-ylmethyl)-6-p-tolyl-4,5-dihydro-2H-pyridazin-3-one (3) with different electrophiles were evaluated. Triazole 3 reacted with alkyl halides in the presence of triethylamine in alcohol to give the corresponding S-substituted derivatives. On the basis of S-chemoselective reactions of triazole 3, a series of amino acid 10a–d and dipeptide derivatives 12a–d were prepared via azide coupling of the corresponding hydrazides 9 and 15 with amino acid ester hydrochlorides, respectively. N-Substituted triazoles 6a–c or 7a–d attached to pyridazin-3-one moiety were successfully formed by the reaction of 3 with activated acrylic acid derivatives or with amines. Antibacterial activities of the synthesized derivatives were investigated through correlation with Escherichia coli FabH inhibitory activities using molecular modeling docking software. The antimicrobial activity of synthesized compounds was evaluated, showing best inhibition zone for N-substituted carboxylic acid 5a and N-substituted nitrile 5c parallel to the molecular modeling studies.