Studies on β-Lactam Antibiotics for Medicinal Purpose. XII. Synthesis and Structure-Activity Relationships of 7β-[α-(4-Ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-substituted acetamido]-7α-methoxycephalosporanic Acids

Abstract

New 7α-methoxycephalosporins, 7β-[α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-substituted acetamido]-7α-methoxycephalosporanic acids (Ia-p) were prepared. They showed a broad antibacterial spectrum, especially a strong antibacterial activity against gram-negative bacilli such as Pseudomonas aeruginosa and Serratia marcescens. In these compounds, 7β-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-phenylacetamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ic), 7β-[D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Id) and 7β-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(2-thienyl) acetamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ig) were selected and evaluated for antibacterial activity, stability against β-lactamase, protective effects on experimental infections.