| Autor: |
Brickner, S. J., Hutchinson, D. K., Barbachyn, M. R., Manninen, P. R., Ulanowicz, D. A., Garmon, S. A., Grega, K. C., Hendges, S. K., Toops, D. S., Ford, C. W., Zurenko, G. E. |
| Zdroj: |
Journal of Medicinal Chemistry; February 2, 1996, Vol. 39 Issue: 3 p673-679, 7p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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