新型β-内酰胺酶抑制剂的合成及其活性研究

摘要：阿维巴坦是一种β-内酰胺酶抑制剂，最近与β-内酰胺酶抗生素头孢他啶联用被批准用于治疗复杂性腹腔感染和复杂性尿路感染。它的成功案例鼓励了许多同系物的发展，其基础是其特殊的二氮杂环辛烷骨架。本文设计合成一系列新型具有二氮杂环辛烷骨架的β-内酰胺酶抑制剂1~6，对β-内酰胺酶抑制剂1~6与头孢他啶抗生素联合使用时产生的抑菌活性进行了研究。研究结果表明，与头孢他啶抗生素联用时对产生TEM-1、AmpC和KPC-2 3种β-内酰胺酶耐药菌表现出抑菌活性，使头孢他啶的抑菌活性增强了2~4倍。

Synthesis and activity research of novel β-lactamase inhibitors

Avibactam, a β-lactamase inhibitor, in combination with ceftazidime was approved, addressing serineβ-lactamase mediated resistance in Enterobacteriaceae and Pseudomonas aeruginosa for treatment of complicatedintra-abdominal infections (cIAI) and complicated urinary tract infections(cUTI). Its therapeutic success encouragedfurther exploration of this particular diazabicyclooctane scaffold. Here, we reported a series of novel β-lactamaseinhibitor that contains a diazabicyclooctane pharmacophore, which was able to restore the activity of ceftazidimeagainst drug resistant bacteria that producing TEM-1, AmpC, and KPC-2 β-lactamase. The MICs of ceftazidime wasimproved by 2~4 fold.