Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections
| العنوان: | Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections |
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| المؤلفون: | Susan K. Hendges, Toops Dana S, Hutchinson Douglas K, Manninen Peter Rudolph, Barbachyn Michael R, Gary E. Zurenko, Stuart A. Garmon, Steven J. Brickner, Ford Charles W, Kevin C. Grega, Debra A. Ulanowicz |
| المصدر: | Journal of Medicinal Chemistry. 39:673-679 |
| بيانات النشر: | American Chemical Society (ACS), 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | Magnetic Resonance Spectroscopy, medicine.drug_class, Antibiotics, Microbial Sensitivity Tests, medicine.disease_cause, Mass Spectrometry, Microbiology, Mice, chemistry.chemical_compound, Dogs, Antibiotic resistance, Anti-Infective Agents, Acetamides, Drug Discovery, medicine, Eperezolid, Animals, Oxazoles, Oxazolidinones, Antibacterial agent, Linezolid, Drug Resistance, Microbial, Combinatorial chemistry, Drug Resistance, Multiple, Rats, Multiple drug resistance, chemistry, Staphylococcus aureus, Molecular Medicine, Vancomycin, Female, Antibacterial activity, medicine.drug |
| الوصف: | Bacterial resistance development has become a very serious clinical problem for many classes of antibiotics. The 3-aryl-2-oxazolidinones are a relatively new class of synthetic antibacterial agents, having a new mechanism of action which involves very early inhibition of bacterial protein synthesis. We have prepared two potent, synthetic oxazolidinones, U-100592 and U-100766, which are currently in clinical development for the treatment of serious multidrug-resistant Gram-positive bacterial infections caused by strains of staphylococci, streptococci, and enterococci. The in vitro and in vivo (po and iv) activities of U-100592 and U-100766 against representative strains are similar to those of vancomycin. U-100592 and U-100766 demonstrate potent in vitro activity against Mycobacterium tuberculosis. A novel and practical asymmetric synthesis of (5S)-(acetamidomethyl)-2-oxazolidinones has been developed and is employed for the synthesis of U-100592 and U-100766. This involves the reaction of N-lithioarylcarbamates with (R)-glycidyl butyrate, resulting in excellent yields and high enantiomeric purity of the intermediate (R)-5-(hydroxymethyl)-2-oxazolidinones. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0aabb6b3bba82a4a3a9cb3b1862302a7 https://doi.org/10.1021/jm9509556 |
| رقم الأكسشن: | edsair.doi.dedup.....0aabb6b3bba82a4a3a9cb3b1862302a7 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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