Synthesis of 1,2,4‐triazolopyridazines, isoxazolofuropyridazines, and tetrazolopyridazines as antimicrobial agents

• Published in: Journal of heterocyclic chemistry 2020-09, Vol.57 (9), p.3461-3474
• Main Authors: Abu‐Hashem, Ameen A., Fathy, Usama, Gouda, Moustafa A.
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Antimicrobial agents; Infrared analysis; NMR; Nuclear magnetic resonance; Pyridazines; Tetrazoles; Triazoles
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4065

Through current and previous researches, it was found that the derivatives of pyridazine, isoxazole, tetrazole, quinazoline, hydrazinyl, and 1,2,4‐triazole have many pharmacological activities. Thus, a series of novel furopyridazinones (7), isoxazolopyridazine (8), sub‐benzylidene‐furopyridazinones (9a‐c), isoxazolofuropyridazines (10a‐c), 3‐chloro‐(pyridin‐4‐ylmethylene)‐dihydropyridazines (11), tetrazolopyridazines (12), pyridazinoquinazolinones (13), piperazinyl/morpholino‐pyridazines (14a,b), hydrazinyl‐pyridazines (15), and 1,2,4‐triazolo‐pyridazines (16a,b) in good yields (72%‐90%) were synthesized from substituted ethyl 4‐oxo‐4‐phenylbutanoate (2), 6‐phenyl‐4,5‐dihydropyridazinone (3), and 6‐phenyl‐4‐(pyridin‐4‐ylmethylene)‐4,5‐dihydropyridazinone (4) as beginning materials. All the chemical structures of the new compounds have been demonstrated by different spectroscopy analyses such as infrared, NMR, mass spectrum, and elemental analysis. Also, the activities of the newly prepared compounds were tested against many types of bacteria and fungi in vitro. Hence, 1,2,4‐triazolopyridazines (16a,b), isoxazolofuropyridazines (10a‐c), tetrazolopyridazines (12), Piperazinyl/morpholinyl‐pyridazines (14a,b) displayed the most efficient antimicrobial activities compared with the cefotaxime sodium and nystatin as standard drugs.