1. Synthesis and evaluation of tylosin-related macrolides modified at the aldehyde function: a new series of orally effective antibiotics.
- Author
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Kirst HA, Toth JE, Debono M, Willard KE, Truedell BA, Ott JL, Counter FT, Felty-Duckworth AM, and Pekarek RS
- Subjects
- Administration, Oral, Aldehydes chemical synthesis, Aldehydes pharmacokinetics, Aldehydes pharmacology, Animals, Bacteria, Anaerobic drug effects, Biological Availability, Chemical Phenomena, Chemistry, Leucomycins pharmacokinetics, Mice, Microbial Sensitivity Tests, Staphylococcus drug effects, Streptococcus drug effects, Structure-Activity Relationship, Leucomycins chemical synthesis
- Abstract
Modification of the aldehyde group in tylosin and related macrolide antibiotics dramatically enhanced the oral efficacy of the derivatives against experimental infections caused by susceptible bacteria in laboratory animals. A large number and wide variety of aldehyde-modified macrolide derivatives were prepared, utilizing the Mitsunobu reaction and other chemical transformations. Evaluation of in vitro and in vivo antimicrobial activity indicated that derivatives of demycarosyltylosin (desmycosin) combined the broadest spectrum of antimicrobial activity with the best efficacy and bioavailability after oral administration.
- Published
- 1988
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