A series of tricyclic β-lactams were synthesized and evaluated for in vitro antibacterial activities against carbapenem-resistant Enterobacterales (CREs). Starting from a reported tricyclic β-lactam that combined the cephalosporin skeleton having a γ-lactone ring with a carboxylic acid group, which was reported as a unique partial structure of Lactivicin, we identified the compound which shows potent antibacterial activities against all tested CREs by introducing sulfoxide. In addition, the sulfoxide-introduced tricyclic β-lactam also shows a strong therapeutic efficacy in the neutropenic mouse lung infection model. These results indicate that the tricyclic β-lactam skeleton will show sufficient therapeutic performance in clinical use and therefore can serve as a scaffold in the search for new antibacterial agents against CREs.

合成了一系列三环 β-内酰胺并进行了体外评价对耐碳青霉烯肠杆菌 (CRE) 的抗菌活性。从报道的三环 β-内酰胺开始，该三环 β-内酰胺将具有 γ-内酯环的头孢菌素骨架与羧酸基团结合起来，据报道，这是 Lactivicin 的独特部分结构，我们确定了对所有测试的 CRE 显示有效抗菌活性的化合物引入亚砜。此外，亚砜引入的三环 β-内酰胺在中性粒细胞减少的小鼠肺部感染模型中也显示出很强的治疗效果。这些结果表明，三环 β-内酰胺骨架在临床使用中将显示出足够的治疗性能，因此可以作为寻找针对 CRE 的新型抗菌剂的支架。