Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors

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• 作者：Yunkyung Jeong ; Jooyeon Lee ; Jae-Sang Ryu ; ^{ryuj@ewha.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Aurora kinase ; Click chemistry ; Hinge-binder ; 1 ; 2 ; 3-Triazole ; Anticancer
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：24
• 期：9
• 页码：2114-2124
• 全文大小：1836 K

文摘

A series of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives were designed, synthesized, and evaluated for the Aurora kinase inhibitory activities. The novel hinge-binder tethered 1,2,3-triazolylsalicylamide scaffold was effectively assembled by Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC). A variety of alkynes with hinge binders were used to search proper structures–binding relationship to the hinge region. The synthesized 1,2,3-triazolylsalicylamide derivatives showed significant Aurora kinase inhibitory activity. In particular, 8a inhibited Aurora A kinase with an IC₅₀ value of 0.284 μM, whereas 8m inhibited Aurora B kinase with an IC₅₀ value of 0.364 μM.