1977 年 97 巻 9 号 p. 987-994
Structure-activity relationship of new semisynthetic penicillins, 6-[D (-)-α-(4-alkyl-2, 3-dioxo-1-piperazinecarboxamido) phenylacetamido] penicillanic acid (I) was investigated. In in vitro antibacterial activity against clinically isolated strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, P. vulgaris, P. morganii, P. rettgeri and Pseudomonas aeruginosa, structure-activity relationship was recognized, except in P. aeruginosa, and antibacterial activity became stronger with the increase in carbon number of the alkyl group in I. Such a tendency was especially marked against K. pneumoniae and S. marcescens. Stability against β-lactamase, blood level, protein binding, acute toxicity and distribution coefficient of I were all related to the number of carbon atoms in the alkyl group of I. In protective effect against experimental infection in mice, T-1220 (I : R=C2H5) was the most effective, and more effective than carbenicillin against P. aeruginosa infection.