头孢唑兰
头孢唑兰 用途与合成方法
Cefozopran (SCE-2787) is a fourth-generation cephalosporin that has good activity against gram-positive organisms including methicillin-susceptible staphylococci, enterococci, and viridans group streptococci; and against gram-negative organisms including hemophilus influenza. Moreover, cefozopran has comparatively good activity against enterococci and P. aeruginosa , which are refractory to other cephalosporins.
Cefozopran (SCE-2787) (5-80 mg/kg; s.c.; twice a day for 5 days; four-week-old ICR male mice) is effective against acute respiratory tract infections caused by Kiebsiella pneumonia DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, Cefozopran (20-80 mg/kg; s.c.; twice a day for 7 days; five-week-old CBA/J female mice) is as effective as Ceftazidime.
13g化合物(Ⅳ)和50ml三氟乙酸,在冰浴冷却下搅拌,再在室温下搅拌30min。浓缩,加入乙酸乙酯,再浓缩。往残液中加入100ml乙醚,过滤收集产生的粉末,干燥,得10g化合物(V),收率92%。
1.1g化合物(V)、1.0g咪唑并[1,2-b]哒嗪和1.1g碘化钾溶于50%乙腈水溶液,在60--70℃下搅拌2h。冷却,经硅胶层析,以丙酮和80%丙酮水溶液洗脱。收集含产物的组分,浓缩。残物经MCl胶CHP 20P柱层析提纯,以2%乙醇水溶液洗脱。收集含产物的组分,浓缩,冻干,得0.2g头孢唑兰,收率17%。
0.4g头孢唑兰溶于1.0ml 0.01mol/L盐酸,经Amberlite XAD-2层析,以0.01mol/L盐酸-乙腈(1:9体积比)洗脱。洗脱液浓缩,加入丙酮,过滤收集产生的粉末,以小量丙酮洗,干燥,得0.25g盐酸头孢唑兰。