ORALLY ACTIVE CEPHALOSPORINS .1. SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 7-BETA-[2-(R)-AMINO-2-PHENYLACETAMIDO]-3-(1H-1,2,3-TRIAZOL-4-YL)ALKYLTHIOMETHYL-3-CEPHEM-4-CARBOXYLIC ACID AND RELATED-COMPOUNDS

The synthesis, antibacterial activity and oral absorbability of 7beta-[2-(R)-amino-2-phenylacetamido]-3-(1H-1,2,3-triazol-4-yl)methylthiomethyl-3-cephem-4-carboxylic acid (1a) and related compounds (1b-p and 2) are described. The replacement of 1,2,3-triazole at the C-3 position of la with other heteroaromatics such as 1,2,4-triazole, imidazole and so on decreased its oral absorbability in mice (1b-j). The oral absorbability was also influenced by the spacer length between C-3 of cephem nucleus and C-4 of 1,2,3-triazole. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a and 1k-p) is discussed. These results suggest that 1,2,3-triazole in the side chain at the C-3 position of cephems plays an important role in good oral absorption through its interaction with the transport system of small intestine.