Synthesis and biological activity of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B.
The synthesis and biological properties of 1-N-[4-(substituted)amidino and guanidino-2-hydroxybutyryl]kanamycins A and B are described. Reaction of 3,3",6'-tri-N-tert-butoxycarbonyl-amikacin with an appropriate amidinating or guanidinating reagent and subsequent deblocking gave a series of amikacin derivatives having an amidino or guanidino group on the 4"'-position. The corresponding kanamycin B analogs were also prepared by a similar procedure. Among these derivatives, 1-N-(4-formamidino- and guanidino-2-hydroxybutyryl)kanamycins A (7a and 7k) and B (11 and 14) exhibited antibacterial activity similar to the corresponding 4-amino analogs. The nephrotoxic potential of selected compounds is also briefly discussed.
Yamasaki
T
T
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Narita
Y
Y
Hoshi
H
H
Aburaki
S
S
Kamei
H
H
Naito
T
T
Kawaguchi
H
H
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy*; D007612:Kanamycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure
C001495:bekanamycin; D007612:Kanamycin