Identification of a Novel Oxazolidinone (U-100480) with Potent Antimycobacterial Activity
| العنوان: | Identification of a Novel Oxazolidinone (U-100480) with Potent Antimycobacterial Activity |
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| المؤلفون: | Sally P. Klemens, Toops Dana S, James O. Kilburn, Susan K. Hendges, Ford Charles W, S. E. Glickman, Gary E. Zurenko, Kevin C. Grega, Steven J. Brickner, Michael H. Cynamon, Hutchinson Douglas K, Barbachyn Michael R |
| المصدر: | Journal of Medicinal Chemistry. 39:680-685 |
| بيانات النشر: | American Chemical Society (ACS), 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | Magnetic Resonance Spectroscopy, medicine.drug_class, SQ109, Microbial Sensitivity Tests, Pharmacology, Antimycobacterial, Mass Spectrometry, Mycobacterium tuberculosis, chemistry.chemical_compound, In vivo, Acetamides, Drug Discovery, medicine, Eperezolid, Animals, Oxazoles, Antibacterial agent, biology, Chemistry, Isoniazid, Biological activity, biology.organism_classification, Anti-Bacterial Agents, Rats, Molecular Medicine, Mycobacterium avium, medicine.drug |
| الوصف: | During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpholine moiety. The rational design, synthesis, and evaluation of the in vitro antimycobacterial activity of these analogues is described. Potent activity against a screening strain of Mycobacterium tuberculosis was demonstrated by 6 and 7 (minimum inhibitory concentrations or MIC's < or = 0.125 micrograms/mL). Oxazolidinones 6 and 8 exhibit MIC90 values of 0.50 micrograms/mL or less against a panel of organisms consisting of five drug-sensitive and five multidrug-resistant strains of M. tuberculosis, with 6 being the most active congener. Potent in vitro activity against other mycobacterial species was also demonstrated by 6. For example, 6 exhibited excellent in vitro activity against multiple clinical isolates of Mycobacterium avium complex (MIC's = 0.5-4 micrograms/mL). Orally administered 6 displays in vivo efficacy against M. tuberculosis and M. avium similar to that of clinical comparators isoniazid and azithromycin, respectively. Consideration of these factors, along with a favorable pharmaco-kinetic and chronic toxicity profile in rats, suggests that 6 (U-100480) is a promising antimycobacterial agent. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbd36c5010853b90f6315fcfa170f5c2 https://doi.org/10.1021/jm950956y |
| رقم الأكسشن: | edsair.doi.dedup.....cbd36c5010853b90f6315fcfa170f5c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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