| Autor: |
Raju B; Versicor Inc., 34790 Ardentech Court, CA 94555, Fremont, USA. raju@versicor.com, Mortell K, Anandan S, O'Dowd H, Gao H, Gomez M, Hackbarth C, Wu C, Wang W, Yuan Z, White R, Trias J, Patel DV |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2003 Jul 21; Vol. 13 (14), pp. 2413-8. |
| DOI: |
10.1016/s0960-894x(03)00393-7 |
| Abstrakt: |
Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. An orthogonally protected beta-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support. This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies. The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity. The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC(50)=2.3 microM), has antibacterial activity (Escherichia coli, MIC=16 microgram/mL), and is efficacious in an E. coli murine septicemia model (ED(50)=16.3mg/kg). |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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