Document Report Card

ID: ALA3272189

Journal: J Med Chem

Title: Orally active esters of cephalosporin antibiotics. Synthesis and biological properties of acyloxymethyl esters of 7-(D-2-amino-2-phenylacetamido)-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid.

Authors: Wheeler WJ, Wright WE, Line VD, Froggé JA.

Abstract: The synthesis of the acetoxymethyl (AOM), pivaloloxymethyl (POM), and phthalidyl (PHTH) esters of 7-[D-(-)-2-amino-2-phenylacetamido]-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid (1a), a broad-spectrum semisynthetic cephalosporin antibiotic, is described. These esters were examined as potential orally active antibiotic prodrugs. The superior oral absorption of the three esters relative to the unesterified parent, 1a, is demonstrated by differential blood levels as well as measurement of the rate at which doses of the ester leave the gastrointestinal tract and appear in the urine. A study of the decreased stability of the three esters relative to 1a at pH 4.5, 6.5, and 7.5 is also presented.

CiteXplore: 21963

DOI: 10.1021/jm00219a009