Wagatsuma M, Seto M, Miyagishima T, Kawazu M, Yamaguchi T, Ohshima S
J Antibiot (Tokyo). 1983 Feb;36(2):147-54. doi: 10.7164/antibiotics.36.147.
In order to improve the antibacterial activity of aminobenzylpenicillin, penicillin derivatives having an asparagine moiety in the 6-acyl side chain (11a approximately g, 12a, b, f, g) were synthesized. The structure-activity relationship of new penicillins, N4-alkyl-asparaginylaminobenzylpenicillins, was investigated. N4-Methyl-D-asparaginylamoxicillin (11a), TA-058, was found to possess a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. In acute toxicity, TA-058 showed good tolerance in mice (LD50 greater than 10 g/kg, i.v.).
为了提高氨基苄青霉素的抗菌活性，合成了在6-酰基侧链含有天冬酰胺部分的青霉素衍生物（11a约g，12a、b、f、g）。研究了新型青霉素N4-烷基-天冬酰胺基氨基苄青霉素的构效关系。发现N4-甲基-D-天冬酰胺基阿莫西林（11a）TA-058对革兰氏阳性菌和革兰氏阴性菌具有广谱抗菌活性。在急性毒性试验中，TA-058在小鼠中表现出良好的耐受性（静脉注射半数致死量大于10 g/kg）。
