4-(2,4-dimethoxyphenyl)pyrimidin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(2,4-dimethoxyphenyl)pyrimidin-2-amine
• 化学式: C₁₂H₁₃N₃O₂
• 分子量: 231.254
• InChiKey: AHYDEALKOXBYFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2,4-dimethoxyphenyl)pyrimidin-2-amine 在 sodium tetrahydroborate 、 四氯化钛 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 Dicyclopropylmethyl-[4-(2,4-dimethoxy-phenyl)-pyrimidin-2-yl]-amine
  参考文献：
  名称：

  Design, synthesis, and SAR of 2-dialkylamino-4-arylpyrimidines as potent and selective corticotropin-releasing factor 1 (CRF 1 ) receptor antagonists

  摘要：

  A series of 2-dialkylamino-4-phenylpyrimidines (7) was designed and synthesized as CRF1 antagonists. SAR studies of this series resulted in the discovery of potent and selective antagonists 7b and 7n bearing a 4-(2,4,6-trisubstituted-phenyl) ring and a bulky 2-(N-bis(cyclopropane)methyl-N-propyl) amino group. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.053
• 作为产物：
  描述：

  2,4-二甲氧基苯乙酮 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 4-(2,4-dimethoxyphenyl)pyrimidin-2-amine
  参考文献：
  名称：

  Design, synthesis, and SAR of 2-dialkylamino-4-arylpyrimidines as potent and selective corticotropin-releasing factor 1 (CRF 1 ) receptor antagonists

  摘要：

  A series of 2-dialkylamino-4-phenylpyrimidines (7) was designed and synthesized as CRF1 antagonists. SAR studies of this series resulted in the discovery of potent and selective antagonists 7b and 7n bearing a 4-(2,4,6-trisubstituted-phenyl) ring and a bulky 2-(N-bis(cyclopropane)methyl-N-propyl) amino group. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.053

文献信息

• Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity
  作者：Junyu Xu、Hongmei Li、Xinren Wang、Jianhang Huang、Shuwen Li、Chenhe Liu、Ruinan Dong、Gaoyuan Zhu、Chunqi Duan、Fei Jiang、Yanmin Zhang、Yuqin Zhu、Tianyi Zhang、Yadong Chen、Weifang Tang、Tao Lu

  DOI：10.1016/j.ejmech.2020.112424

  日期：2020.8

  Specific inhibition of CDK9 is considered a promising strategy for developing effective anticancer therapeutics. However, most of the reported CDK9 inhibitors are still at an early stage of development and lack selectivity against other CDKs. Herein, we discovered coumarin derivative 30i as a potent CDK9 inhibitor with high selectivity (8300-fold over CDK7). Binding mode analysis illustrated that the substituent coumarin moiety is a critical group for CDK9 selectivity by occupying a flexible hinge/alpha D region, which is sterically hindered in other CDKs. Compound 30i showed excellent cellular antiproliferative activity, moderate pharmacokinetic property and low hERG inhibition. Moreover, 30i significantly induced tumour growth inhibition in a dose-dependent manner without causing an obvious loss of body weight in an MV4-11 xenograft mice model. Altogether, these results suggest that 30i may serve as a potential acute myeloid leukaemia (AML) therapeutics by selectively targeting CDK9. (C) 2020 Elsevier Masson SAS. All rights reserved.