KY-109, a new bifunctional pro-drug of a cephalosporin. Chemistry, physico-chemical and biological properties.
(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 7-[D-O-(L-alanyl)mandelamido]-3-[[(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 was found to possess the desired factors for an orally active pro-drug, that is, 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.
D000284:Administration, Oral; D000818:Animals; D002511:Cephalosporins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D007408:Intestinal Absorption; D051381:Rats
D002511:Cephalosporins; C045380:cefcanel daloxate