Design, synthesis, and evaluation of stable and taste-free erythromycin proprodrugs

Pranab K. Bhadra, Gareth A. Morris, Jill Barber

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Erythromycin A is normally formulated for children as its 2′-ethyl succinate, a taste-free prodrug. Unfortunately, the prodrug hydrolyzes at a measurable rate in the medicine bottle, leading to the vile-tasting erythromycin. We have prepared derivatives of erythromycin B as putative paediatric prodrugs, taking advantage of the much improved acid stability of erythromycin B relative to erythromycin A. Thus, erythromycin B enol ether ethyl succinate is very poorly soluble in water, and its hydrolysis is undetectable in conditions resembling the medicine bottle. In acid, however, it converts rapidly to erythromycin B 2′-ethyl succinate, and this is in turn hydrolyzed to erythromycin B in neutral and basic conditions. Derivatives of erythromycin B enol ether are therefore proposed as taste-free proprodrugs of erythromycin B. © 2005 American Chemical Society.
    Original languageEnglish
    Pages (from-to)3878-3884
    Number of pages6
    JournalJournal of Medicinal Chemistry
    Volume48
    Issue number11
    DOIs
    Publication statusPublished - 2 Jun 2005

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