Based on insight from the X-ray crystal structure of human chymase in complex with compound 1, a lactam carbonyl of the diazepane core was exchanged with O-substituted oxyimino group, leading to amidoxime derivatives. This modification resulted in highly potent chymase inhibitors, such as O-phenylamidoxime 5f. X-ray crystal structure analysis indicated that compound 5f induced movement of the Leu99 and Tyr94 side chains at the S2 site, and the increase in inhibitory activity of O-phenyl amidoxime derivatives suggested that the O-phenyl moiety interacted with the Tyr94 residue. Surface plasmon resonance experiments showed that compound 5f had slower association and dissociation kinetics and the calculated residence time of compound 5f to human chymase was extended compared to that of amide compound 1.

基于人糜酶与化合物1复合的X射线晶体结构的见解，将二氮杂环庚烷核心的内酰胺羰基与O-取代的氧亚氨基基团交换，从而得到a肟肟衍生物。这种修饰导致了高效的糜酶抑制剂，例如O- phenylamidoxime 5f。X射线晶体结构分析表明，化合物5f诱导Leu99和Tyr94侧链在S2位点运动，O-苯基a胺肟衍生物的抑制活性增加表明O-苯基部分与Tyr94残基相互作用。表面等离振子共振实验表明，化合物5f具有较慢的缔合和解离动力学，与酰胺化合物1相比，化合物5f在人糜酶中的计算停留时间延长。