Novel cyclic-imide peptidomimetics as aminopeptidase N inhibitors. Design, chemistry and activity evaluation. Part I

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• 作者：Qianbin Li ; Hao Fang ; Xuejian Wang ; Liping Hu ; Wenfang Xu
• 关键词：Aminopeptidase N ; Cyclic-imide ; Peptidomimetics ; Anti-tumor
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：44
• 期：12
• 页码：4819-4825
• 全文大小：503 K

文摘

A series of aminopeptidase inhibitors with cyclic-imide scaffold are described. The biological characterization for the piperidinedione analogues revealed that most compounds displayed high inhibitory activity against APN. Among which 4l and 6 showed potent inhibition against APN with the IC₅₀ value of 5.2 μM and 3.1 μM, respectively. In addition, 6 also displayed good activity in HL-60 cell assay and in vivo anti-metastasis assay. This interesting activity profile may also guide the design of new, specific inhibitors of target mammalian aminopeptidases with ‘one-zinc’ active site.