Chemical modification of fortimicins: preparation of 4-N-substituted fortimicin B.
Among the new aminoglycoside antibiotic family for fortimicins, components A, C and D have higher activity compared to their 4-N-deacylated components B and KE. Synthesis and antibacterial activities of 4-N-acyl- and 4-N-alkyl-fortimicin B derivatives are described. 4-N-Acylfortimicin B's, which are relatively unstable in alkaline conditions, were converted to stable 4-N-alkyl derivatives with diborane. The activity is greatly affected by the 4-N-substituents, and the presence of hydrophilic group(s) is necessary to confer activity on the derivatives. 4-N-(2-Aminoethyl)-, 4-N-(4-amino-2-hydroxybutyl)- and 4-N-(2-hydroxy-4-methylaminobutyl)-fortimicin B are the most potent compounds among them.
D000617:Aminoglycosides / Q000138:chemical synthesis / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents