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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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
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author Xiang, Pu
Jie, Hui
Zhou, Yang
Yang, Bo
Wang, Hui-Juan
Hu, Jing
Hu, Jian
Yang, Sheng-Yong
Zhao, Ying-Lan
author_facet Xiang, Pu
Jie, Hui
Zhou, Yang
Yang, Bo
Wang, Hui-Juan
Hu, Jing
Hu, Jian
Yang, Sheng-Yong
Zhao, Ying-Lan
author_sort Xiang, Pu
collection PubMed
description 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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spelling pubmed-62727112019-01-07 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors Xiang, Pu Jie, Hui Zhou, Yang Yang, Bo Wang, Hui-Juan Hu, Jing Hu, Jian Yang, Sheng-Yong Zhao, Ying-Lan Molecules Article 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. MDPI 2015-04-27 /pmc/articles/PMC6272711/ /pubmed/25923513 http://dx.doi.org/10.3390/molecules20057620 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiang, Pu
Jie, Hui
Zhou, Yang
Yang, Bo
Wang, Hui-Juan
Hu, Jing
Hu, Jian
Yang, Sheng-Yong
Zhao, Ying-Lan
5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
title 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
title_full 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
title_fullStr 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
title_full_unstemmed 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
title_short 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
title_sort 5-methoxyquinoline derivatives as a new class of ezh2 inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272711/
https://www.ncbi.nlm.nih.gov/pubmed/25923513
http://dx.doi.org/10.3390/molecules20057620
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