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

• Published in: YAKUGAKU ZASSHI Vol. 102; no. 7; pp. 617 - 628
• Main Authors: TAKANO, SHUNTARO, TAKAKURA, ISAMU, OCHIAI, HIROKAZU, MOMONOI, KAISHU, TANAKA, KIYOSHI, SHIBATA, HISANARI, KOMATSU, MIWAKO, YASUDA, TAKASHI, TAI, MASARU, FUKUOKA, YOSHIKAZU, SAIKAWA, ISAMU
• Format: Journal Article
• Language: Japanese
• Published: The Pharmaceutical Society of Japan 25.07.1982
• Subjects: 7β-[α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-substituted acetamido]-7α-methoxycephalosporanic acids; antibacterial activity; antibiotics; protective effect on experimental infection; semisynthetic 7α-methoxycephalosporins; stability against β-lactamase; α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-substituted acetic acids
• ISSN: 0031-6903; 1347-5231
• DOI: 10.1248/yakushi1947.102.7_617

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.