6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(piperidin-4-yl)quinazolin-4-amine | 1197196-56-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(piperidin-4-yl)quinazolin-4-amine
• 英文别名: 6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-piperidin-4-ylquinazolin-4-amine
• CAS: 1197196-56-7
• 化学式: C₂₁H₃₂N₆O₂
• 分子量: 400.524
• InChiKey: WOCRGNRTXJWSBP-UHFFFAOYSA-N

物化性质

• 沸点：
  594.3±60.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 在 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 生成 6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(piperidin-4-yl)quinazolin-4-amine
  参考文献：
  名称：

  [EN] HISTONE DEACETYLASE AND HISTONE METHYLTRANSFERASE INHIBITORS AND METHODS OF MAKING AND USE OF THE SAME
  [FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE ET D'HISTONE MÉTHYLTRANSFÉRASE ET LEURS PROCÉDÉS DE PRODUCTION ET D'UTILISATION

  摘要：

  化合物的化学式（I）是组蛋白去乙酰化酶（HDACs）和组蛋白甲基转移酶G9a的双重抑制剂，这两者都是癌症发展中关键的翻译后修饰酶。

  公开号：

  WO2018005799A1

文献信息

• Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines.
  作者：Feng Liu、Xin Chen、Abdellah Allali-Hassani、Amy M. Quinn、Tim J. Wigle、Gregory A. Wasney、Aiping Dong、Guillermo Senisterra、Irene Chau、Alena Siarheyeva、Jacqueline L. Norris、Dmitri B. Kireev、Ajit Jadhav、J. Martin Herold、William P. Janzen、Cheryl H. Arrowsmith、Stephen V. Frye、Peter J. Brown、Anton Simeonov、Masoud Vedadi、Jian Jin

  DOI：10.1021/jm100478y

  日期：2010.8.12

  Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a-10 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. On the basis of the structural insights revealed by this cocrystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison K(i) = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date.
• Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a
  作者：Feng Liu、Xin Chen、Abdellah Allali-Hassani、Amy M. Quinn、Gregory A. Wasney、Aiping Dong、Dalia Barsyte、Ivona Kozieradzki、Guillermo Senisterra、Irene Chau、Alena Siarheyeva、Dmitri B. Kireev、Ajit Jadhav、J. Martin Herold、Stephen V. Frye、Cheryl H. Arrowsmith、Peter J. Brown、Anton Simeonov、Masoud Vedadi、Jian Jin

  DOI：10.1021/jm901543m

  日期：2009.12.24

  SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as it potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. The cocrystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin remodeling.
• [EN] HISTONE DEACETYLASE AND HISTONE METHYLTRANSFERASE INHIBITORS AND METHODS OF MAKING AND USE OF THE SAME<br/>[FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE ET D'HISTONE MÉTHYLTRANSFÉRASE ET LEURS PROCÉDÉS DE PRODUCTION ET D'UTILISATION
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2018005799A1

  公开（公告）日：2018-01-04

  The compounds of formula (I) are dual inhibitors of the enzymes histone deacetylases (HDACs) and histone methyltransferase G9a, both of which are key posttranslational enzymes in cancer development.

  化合物的化学式（I）是组蛋白去乙酰化酶（HDACs）和组蛋白甲基转移酶G9a的双重抑制剂，这两者都是癌症发展中关键的翻译后修饰酶。