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

Pranab K Bhadra, Gareth A Morris, Jill Barber

School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, M13 9PL, UK.

Journal of medicinal chemistry 2005 Jun 2

filter terms:

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.

Citation

Pranab K Bhadra, Gareth A Morris, Jill Barber. Design, synthesis, and evaluation of stable and taste-free erythromycin proprodrugs. Journal of medicinal chemistry. 2005 Jun 2;48(11):3878-84