5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors

A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displ...

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Detalles Bibliográficos
Autores principales: Xiang, Pu, Jie, Hui, Zhou, Yang, Yang, Bo, Wang, Hui-Juan, Hu, Jing, Hu, Jian, Yang, Sheng-Yong, Zhao, Ying-Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272711/
https://www.ncbi.nlm.nih.gov/pubmed/25923513
http://dx.doi.org/10.3390/molecules20057620
Descripción
Sumario:A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC(50) value of 1.2 μM against EZH2, decreased global H3K27me3 level in cells and also showed good anti-viability activities against two tumor cell lines. Due to the low molecular weight and the fact that no quinoline derivative has been reported as an EZH2 inhibitor, this compound could serve as a lead compound for further optimization.

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