咪唑并[1,2- a]吡啶封端的选择性 HDAC6 抑制剂的多组分合成及结合模式。
Multicomponent Synthesis and Binding Mode of Imidazo[1,2- a]pyridine-Capped Selective HDAC6 Inhibitors.
机构信息
Institut für Pharmazie , Universität Leipzig , Brüderstraße 34 , 04103 Leipzig , Germany.
Institut für Pharmazeutische und Medizinische Chemie , Heinrich-Heine-Universität Düsseldorf , Universitätsstr. 1 , 40225 Düsseldorf , Germany.
出版信息
Org Lett. 2018 Jun 1;20(11):3255-3258. doi: 10.1021/acs.orglett.8b01118. Epub 2018 May 23.
Abstract
The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode.
摘要
本文报道了一种基于咪唑并[1,2-a]吡啶的组蛋白去乙酰化酶抑制剂的小型文库的多组分合成。生物评价发现了先导化合物 MAIP-032，它是一种选择性 HDAC6 抑制剂，具有有前景的抗癌活性。与 MAIP-032 结合的斑马鱼 HDAC6 催化结构域 2 的 X 射线结构揭示了一种单价锌结合模式。
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