KY-109, a new bifunctional pro-drug of a cephalosporin. Chemistry, physico-chemical and biological properties.

Abstract
(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 7-[D-O-(L-alanyl)mandelamido]-[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-3-cephem-4-carboxylate hydrochloride (KY-109) was synthesized as a bifunctional pro-drug designed to improve the oral absorption of the parent drug (KY-087), a cephalosporin similar in activity to cefamandole. The pro-drug possesses the desired factors for an orally active pro-drug, i.e., appropriate solubility, lipophilicity and ease hydrolysis into the parent drug. As predicted from these factors, the pro-drug when administered orally to rats was well absorbed and gave high blood levels of the parent drug.