Iimura S, Imae K, Hasegawa T, Okita T, Tamaoka M, Murata S, Kamachi H, Kamei H
Bristol-Myers Squibb Research Institute, Bristol-Myers Squibb K.K., Tokyo.
J Antibiot (Tokyo). 1993 May;46(5):850-7. doi: 10.7164/antibiotics.46.850.
7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3- [propen-1-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6,7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave well-balanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.
合成了在丙烯基的3-位上具有多种杂环儿茶酚的7-[(Z)-2-(2-氨基噻唑-4-基)-2-甲氧基-(或羟基)-亚氨基乙酰胺基]-3-[丙烯-1-基]-头孢菌素。其中，6,7-二羟基异喹啉衍生物2a和2b在给小鼠肌肉注射后显示出非常高且持久的血药浓度，并且其体内抗菌活性高于根据其体外活性所预期的值。前一种头孢菌素(2a)具有平衡的体外和体内抗菌谱，包括抗耐甲氧西林金黄色葡萄球菌(MRSA)活性。后一种头孢菌素(2b)对革兰氏阳性菌也显示出良好的体外和体内活性，特别是对MRSA菌株金黄色葡萄球菌A15036，其体内活性与万古霉素相当，但缺乏抗假单胞菌活性。
