β-ラクタム系抗生物質の薬学的研究(第9報)7-[D(-)-α-(4-Ethyl-2,3-dioxo-1-piperazinecarboxamido)phenylacetamido]cephalosporanic Acid類の構造活性相関

概要

論文の詳細を見る
The structure-activity relationships of new semisynthetic cephalosporins, 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido) phenylacetamido] cephalosporanic acids (Ia-h) were investigated. Ia-h were found to possess a broad spectrum of antibacterial activity against clinical isolates of gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa, 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl)-acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (Ih) showed the strongest activity. Ia-h were more stable than Cefazolin (CEZ) to cephalosporinases. In acute toxicity, 3-acetoxymethyl-7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-cephem-4-carboxylic acid (Ib), 7-[D(-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-[(1,3,4-thiadiazol-2-yl) thiomethyl]-3-cephem-4-carboxylic acid (Id) and Ih showed good tolerance upon i.v. administration to mice. Serum protein binding, serum level and urinary excretion of the three compounds varied remarkably among animal species. Regarding the protective effect against experimental infection in mice, Ih was the most effective among the three compounds, and more effective than CEZ against gramnegative bacterial infection.
社団法人日本薬学会の論文
1979-11-25