Okonogi K, Miyake A
Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd.
Nihon Rinsho. 1997 May;55(5):1261-5.
Since infectious diseases are caused by various bacteria and most of them are treated empirically, broad-spectrum antibiotics are required. To expand the spectrum, an imidazopyridazinium group and aminothiadiazole group were introduced to 3- and 7-side chain of cephem nucleus, respectively. The resulting compound, cefozopran, was able to permeate not only outer membrane of Pseudomonas aeruginosa but also envelope of gram-positive bacteria, which functioned as a barrier to antipseudomonal cephalosporins, and showed potent activity against wide variety of bacteria including those which produced a large amount of cephalosporinase and were resistant to third-generation cephalosporins. In spite of the broad antibacterial spectrum, cefozopran only weakly affected gastrointestinal flora of mice and prevented colonization by MRSA.
由于传染病是由各种细菌引起的，并且大多数传染病是根据经验进行治疗的，因此需要使用广谱抗生素。为了扩大抗菌谱，分别将咪唑并哒嗪鎓基团和氨基噻二唑基团引入到头孢烯核的3位和7位侧链上。由此得到的化合物头孢唑兰不仅能够穿透铜绿假单胞菌的外膜，还能够穿透革兰氏阳性菌的包膜（革兰氏阳性菌的包膜是抗假单胞菌头孢菌素的屏障），并且对多种细菌显示出强大的活性，包括那些产生大量头孢菌素酶并对第三代头孢菌素有抗性的细菌。尽管头孢唑兰具有广泛的抗菌谱，但它对小鼠胃肠道菌群的影响很小，并且能够防止耐甲氧西林金黄色葡萄球菌（MRSA）的定植。
