Synthesis, antimicrobial activity and in vivo fluorine NMR of a hexafluorinated derivative of tilmicosin.
A new fluorinated analog of tilmicosin was synthesized by the reductive amination of desmycosin with 3,5-bis(trifluoromethyl)piperidine. Despite an apparently small change in structure, the fluorinated analog had much less in vitro antimicrobial activity than tilmicosin and it failed to protect 3-day old chicks against a Pasteurella multocida challenge at 64 mg/kg sc. In a preliminary in vivo fluorine NMR experiment in a female Sprague-Dawley rat, a 19F NMR signal was detected in the liver one hour after ip administration of the fluorinated compound. Therefore, although this fluorinated derivative had less antimicrobial activity than tilmicosin, it may nevertheless provide a suitable model of tilmicosin for pharmacokinetic studies using in vivo fluorine NMR.
Creemer
L C
LC
Lilly Research Laboratories, Greenfield, IN 46140, USA.
Kirst
H A
HA
Shryock
T R
TR
Campbell
J B
JB
Webb
A G
AG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002645:Chickens; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010326:Pasteurella Infections / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D015645:Tylosin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; C095344:hexafluorotilmicosin; D015645:Tylosin