SYNTHESIS, ANTIMICROBIAL ACTIVITY AND IN-VIVO FLUORINE NMR OF A HEXAFLUORINATED DERIVATIVE OF TILMICOSIN

A new fluorinated analog of tilmicosin was synthesized by the reductiv e amination of desmycosin with 3,5-bis(trifluoromethyl)piperidine. Des pite an apparently small change in structure, the fluorinated analog h ad much less in vitro antimicrobial activity than tilmicosin and it fa iled to protect 3-day old chicks against a Pasteurella multocida chall enge at 64 mg/kg sc. In a preliminary in vivo fluorine NMR experiment in a female Sprague-Dawley rat, a F-19 NMR signal was detected in the liver one hour after ip administration of the fluorinated compound. Th erefore, although this fluorinated derivative had less antimicrobial a ctivity than tilmicosin, it may nevertheless provide a suitable model of tilmicosin for pharmacokinetic studies using in vivo fluorine NMR.