Structural studies on tazobactam

Tazobactam (3, C10H12N4O5S) is an effective inhibitor of bacterial beta-lactamases. It crystallizes with unit cell dimensions a = 10.230 (2) A, b = 14.396 (2) A, and c = 17.291 (2) A in space group P2(1)2(1)2(1). Compared to the related inhibitor sulbactam (2), which lacks the triazole ring, crystal...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1991-07, Vol.34 (7), p.1944-1947
Main Authors: Toomer, Carol A, Schwalbe, Carl H, Ringan, Neil S, Lambert, Peter A, Lowe, Philip R, Lee, Ving J
Format: Article
Language:English
Subjects:
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
beta-Lactamase Inhibitors
Biological and medical sciences
Computer Simulation
Medical sciences
Models, Chemical
Molecular Conformation
Penicillanic Acid - chemistry
Penicillanic Acid - pharmacology
Pharmacology. Drug treatments
Tazobactam
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Summary:Tazobactam (3, C10H12N4O5S) is an effective inhibitor of bacterial beta-lactamases. It crystallizes with unit cell dimensions a = 10.230 (2) A, b = 14.396 (2) A, and c = 17.291 (2) A in space group P2(1)2(1)2(1). Compared to the related inhibitor sulbactam (2), which lacks the triazole ring, crystalline tazobactam exhibits very similar beta-lactam geometry and the same S(1) envelope conformation of the thiazolidine ring. However, in both independent molecules of 3 a triazole ring nitrogen atom accepts an intermolecular hydrogen bond; similar interaction by this moiety of 3 with a hydrogen-bond donor on the enzyme, which is impossible for 2, could account for its enhanced inhibitory power. Semiempirical molecular orbital calculations show pronounced negative potential there. Molecular mechanics supports the hypothesis that the carboxyl group can rotate freely and the triazole ring can "flip".
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00111a003