2-chloro-N-cyclopropyl-6,7-dimethoxyquinazolin-4-amine | 938524-27-7

• 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: 2-chloro-N-cyclopropyl-6,7-dimethoxyquinazolin-4-amine
• CAS: 938524-27-7
• 化学式: C₁₃H₁₄ClN₃O₂
• mdl: MFCD09726519
• 分子量: 279.726
• InChiKey: IJKGMMZVFBFQTG-UHFFFAOYSA-N

物化性质

• 沸点：
  408.9±45.0 °C(Predicted)
• 密度：
  1.407±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-甲基高哌嗪 、 2-chloro-N-cyclopropyl-6,7-dimethoxyquinazolin-4-amine 在 盐酸 作用下， 以 1,4-二氧六环 、 异丙醇 为溶剂， 以79%的产率得到N-cyclopropyl-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
  参考文献：
  名称：

  Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a

  摘要：

  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.

  DOI：

  10.1021/jm901543m
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 、 环丙胺 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2-chloro-N-cyclopropyl-6,7-dimethoxyquinazolin-4-amine
  参考文献：
  名称：

  Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines.

  摘要：

  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.

  DOI：

  10.1021/jm100478y

文献信息

• QUINAZOLINE DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS
  申请人：Knust Henner

  公开号：US20100125078A1

  公开（公告）日：2010-05-20

  The present invention relates to a compounds of formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , and n are as defined herein and to a pharmaceutically active salt, a racemic mixture, an enantiomer, an optical isomer or a tautomeric form thereof. The present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

  本发明涉及一种具有以下式I的化合物 其中 R 1 ，R 2 ，R 3 ，R 4 ，R 5 和n如本文所定义，并且涉及其药用活性盐，外消旋混合物，对映体，光学异构体或其互变异构体形式。本化合物是治疗抑郁症、疼痛、精神病、帕金森病、精神分裂症、焦虑症和注意力缺陷多动障碍（ADHD）的高潜力NK-3受体拮抗剂。
• 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.
• US8318749B2
  申请人：——

  公开号：US8318749B2

  公开（公告）日：2012-11-27
• 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.