6-chloro-N⁴-(3,4-dimethoxy-phenyl)-pyrimidine-4,5-diamine | 870257-98-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-chloro-N⁴-(3,4-dimethoxy-phenyl)-pyrimidine-4,5-diamine
• 英文别名: 6-chloro-N⁴-(3’,4’-dimethoxyphenyl)pyrimidine-4,5-diamine；6-chloro-4-N-(3,4-dimethoxyphenyl)pyrimidine-4,5-diamine
• CAS: 870257-98-0
• 化学式: C₁₂H₁₃ClN₄O₂
• 分子量: 280.714
• InChiKey: LSHLQUWXSRZNAP-UHFFFAOYSA-N

物化性质

• 沸点：
  416.9±45.0 °C(Predicted)
• 密度：
  1.374±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-N⁴-(3,4-dimethoxy-phenyl)-pyrimidine-4,5-diamine 在 magnesium sulfate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 8,9-dimethoxy-N-[(1R)-1-phenylethyl]-6,11-dihydro-5H-pyrimido[4,5-b][1,4]benzodiazepin-4-amine
  参考文献：
  名称：

  Novel tricyclic azepine derivatives: Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase

  摘要：

  Novel tricyclic derivatives containing an oxazepine, thiazepine, or diazepine ring were studied for their EGFR tyrosine kinase inhibitory activity. While the oxazepines were in general more potent than thiazepines, the diazepines displayed somewhat different structure-activity relationships. Moreover, the diazepines, in contrast to the oxazepines, showed appreciable inhibitory activity against the KDR tyrosine kinase. Furthermore, both oxazepines and diazepines demonstrated significant ability to inhibit autophosphorylation of EGFR in DiFi cells (generally, IC50 values in the single-digit micromolar to submicromolar range). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.031
• 作为产物：
  描述：

  4,6-二氯-5-氨基嘧啶 、 3,4-二甲氧基苯胺 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 以45%的产率得到6-chloro-N⁴-(3,4-dimethoxy-phenyl)-pyrimidine-4,5-diamine
  参考文献：
  名称：

  通过Pictet-Spengler环化制备取代的嘧啶并[4,5 - b ] -1,4-苯并a氮平，硫氮平和地西平

  摘要：

  使用Pictet-Spengler环化作为关键步骤，可以实现标题化合物的合成，这些化合物已被用作某些受体酪氨酸激酶的抑制剂。

  DOI：

  10.1021/jo051419g

文献信息

• Preparation of Substituted Pyrimido[4,5-<i>b</i>]-1,4-benzoxazepines, Thiazepines, and Diazepines via a Pictet−Spengler Cyclization
  作者：Matthew A. J. Duncton、Leon M. Smith、Sabina Burdzovic-Wizeman、Aaron Burns、Hu Liu、Yunyu Mao、Wai C. Wong、Alexander S. Kiselyov

  DOI：10.1021/jo051419g

  日期：2005.11.1

  A synthesis of the title compounds, which have found use as inhibitors of certain receptor tyrosine kinases, was achieved using a Pictet−Spengler cyclization as a key step.

  使用Pictet-Spengler环化作为关键步骤，可以实现标题化合物的合成，这些化合物已被用作某些受体酪氨酸激酶的抑制剂。
• Purine analogs as phosphatidylinositol 4-kinase IIIβ inhibitors
  作者：Michal Šála、Martin Kögler、Pavla Plačková、Ivana Mejdrová、Hubert Hřebabecký、Eliška Procházková、Dmytro Strunin、Gary Lee、Gabriel Birkus、Jan Weber、Helena Mertlíková-Kaiserová、Radim Nencka

  DOI：10.1016/j.bmcl.2016.04.002

  日期：2016.6

  We report on an extensive structure–activity relationship study of novel PI4K IIIβ inhibitors. The purine derivative of the potent screening hit T-00127-HEV1 has served as a suitable starting point for a thorough investigation of positions 8 and 2. While position 8 of the purine scaffold can only bear a small substituent to maintain the inhibitory activity, position 2 is opened for extensive modification

  我们报道了新型PI4KIIIβ抑制剂的广泛的构效关系研究。强效筛选命中的T-00127-HEV1的嘌呤衍生物已作为彻底研究位置8和2的合适起点。而嘌呤支架的位置8仅可带有一个小的取代基以维持抑制活性， 2被打开以进行广泛的修饰并且可以容纳甚至被取代的苯环而不会损失PI4KIIIβ抑制活性。这些经验观察与我们的对接研究的结果很好地相关，这表明位置2指向溶液，可以为与酶的远程残基相互作用提供必要的空间，而位置8周围的空腔则受到严格限制。
• Novel tricyclic azepine derivatives: Biological evaluation of pyrimido[4,5-b]-1,4-benzoxazepines, thiazepines, and diazepines as inhibitors of the epidermal growth factor receptor tyrosine kinase
  作者：Leon Smith、Wai C. Wong、Alexander S. Kiselyov、Sabina Burdzovic-Wizemann、Yunyu Mao、Yongjiang Xu、Matthew A.J. Duncton、Ki Kim、Evgueni L. Piatnitski、Jacqueline F. Doody、Ying Wang、Robin L. Rosler、Daniel Milligan、John Columbus、Chris Balagtas、Sui Ping Lee、Andrey Konovalov、Yaron R. Hadari

  DOI：10.1016/j.bmcl.2006.07.031

  日期：2006.10

  Novel tricyclic derivatives containing an oxazepine, thiazepine, or diazepine ring were studied for their EGFR tyrosine kinase inhibitory activity. While the oxazepines were in general more potent than thiazepines, the diazepines displayed somewhat different structure-activity relationships. Moreover, the diazepines, in contrast to the oxazepines, showed appreciable inhibitory activity against the KDR tyrosine kinase. Furthermore, both oxazepines and diazepines demonstrated significant ability to inhibit autophosphorylation of EGFR in DiFi cells (generally, IC50 values in the single-digit micromolar to submicromolar range). (c) 2006 Elsevier Ltd. All rights reserved.