Studies on prodrugs. II. Preparation and characterization of (5-substituted 2-Oxo-1,3-dioxolen-4-yl)methyl esters of ampicillin.

Abstract

(5-Substituted 2-oxo-1,3-dioxolen-4-yl)methyl esters were designed as a new type of ampicillin prodrug. These esters were prepared and confirmed to produce higher blood levels of ampicillin than ampicillin trihydrate itself after oral adminstration to mice. The compounds which produced particularly high blood levels of ampicillin were found to be hydrolyzed readily in blood in vitro. Ampicillin (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester hydrochloride (KBT-1585) showed the best oral absorbability in mice.