SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF 7β-[2-(2-AMINOTHIAZOL-4-YL)ACETAMIDO] CEPHALOSPORIN DERIVATIVES

V. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7β-[2-(2-AMINOTHIAZOL-4-YL)-2-METHOXYIMINOACETAMIDO]-CEPHALOSPORIN DERIVATIVES AND RELATED COMPOUNDS

Abstract

In order to improve the antibacterial activity of 7β-[2-(2-aminothiazol-4-yl)acetamido]-cephalosporins new derivatives having a methoxyimino moiety in the 7-acyl side chain and related compounds were synthesized. Of these, 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido] cephalosporins were found to possess excellent activity against a variety of Gram-positive and Gram-negative bacteria including β-lactamase-producing strains. An extensive study of structure-activity relationships led to the selection of 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-ceph-3-em-4-carboxylic acid, SCE-1365, for further biological and clinical evaluation.