Synthesis, structure and antibacterial activity of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives

• Published in: Bioorganic & medicinal chemistry 2008-04, Vol.16 (7), p.4075-4082
• Main Authors: Liu, Xin-Hua, Cui, Pin, Song, Bao-An, Bhadury, Pinaki S., Zhu, Hai-Liang, Wang, Shi-Fan
• Format: Article
• Language: English
• Subjects: 5-Arylpyrazole; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Crystallography, X-Ray; DNA Gyrase - metabolism; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Escherichia coli - drug effects; Escherichia coli - enzymology; Esters - chemical synthesis; Esters - chemistry; Esters - pharmacology; Ethane - chemistry; Hydrogen - chemistry; Medical sciences; Models, Molecular; Molecular Structure; Oxime ester; Oximes - chemistry; Pharmacology. Drug treatments; Pyrazoles - chemistry; Staphylococcus aureus - drug effects; Staphylococcus aureus - enzymology; Structure-Activity Relationship; Synthesis; Topoisomerase II Inhibitors
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.01.035

A series of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives and the unusual heterocyclic compound 2,5,5-trimethyl-1,5,6,10b-tetrahydropyrazolo[5,1- a]isoquinoline are synthesized. The title compounds 14 and 26c showed potent antibacterial activities against Staphylococcus aureus and Escherichia coli which was superior to the positive control penicillin. A series of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives are synthesized. The results show that compounds 14 and 26c can strongly inhibit Staphylococcus aureus DNA gyrase and Escherichia coli DNA gyrase (with IC 50 of 0.25 and 0.125 μg/mL against S. aureus DNA gyrase, 0.125 and 0.25 μg/mL against E. coli DNA gyrase). On the basis of the biological results, structure–activity relationships are also discussed.