N-(3-bromophenyl)-2,5-dichloropyrimidin-4-amine | 1352244-15-5

• 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: N-(3-bromophenyl)-2,5-dichloropyrimidin-4-amine
• 英文别名: (3-bromophenyl)-(2,5-dichloropyrimidin-4-yl)amine
• CAS: 1352244-15-5
• 化学式: C₁₀H₆BrCl₂N₃
• 分子量: 318.988
• InChiKey: OWJSRUSBPUFXRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-bromophenyl)-2,5-dichloropyrimidin-4-amine 在 盐酸 、 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 1,4-二氧六环 、 甲乙醚 、 乙腈 为溶剂， 反应 16.5h， 生成 N4-(5-bromo-2-methoxyphenyl)-5-chloro-N2-(3-vinylphenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Design, Synthesis, and Anaplastic Lymphoma Kinase (ALK) Inhibitory Activity for a Novel Series of 2,4,8,22-Tetraazatetracyclo[14.3.1.1^3,7.1^9,13]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene Macrocycles

  摘要：

  A novel set of 2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles were prepared as potential anaplastic lymphoma kinase (ALK) inhibitors, designed to rigidly lock an energy-minimized bioactive conformation of the diaminopyrimidine (DAP) scaffold, a well-documented kinase platform. From 13 analogues prepared, macrocycle 2m showed the most promising in vitro ALK enzymatic (IC50 = 0.5 nM) and cellular (IC50 = 10 nM) activities. In addition, macrocycle 2m exhibited a favorable kinase selectivity preference for inhibition of ALK relative to the highly homologous insulin receptor (IR) kinase (IR/ALK ratio of 173). The inclusive in vitro biological results for this set of macrocycles validate this scaffold as a viable kinase template and further corroborate recent DAP/ALK solid state studies indicating that the inverted "U" shaped conformation of the acyclic DAPs is a preferred bioactive conformation.

  DOI：

  10.1021/jm201333e
• 作为产物：
  描述：

  2,4,5-三氯嘧啶 、 间溴苯胺 在 四丁基碘化铵 作用下， 以 二甲基亚砜 为溶剂， 反应 3.08h， 以72%的产率得到N-(3-bromophenyl)-2,5-dichloropyrimidin-4-amine
  参考文献：
  名称：

  含有组蛋白脱乙酰酶抑制剂的 5-chloro-4-((取代的苯基)氨基)嘧啶的发现和 SAR 分析

  摘要：

  摘要 组蛋白去乙酰化酶 (HDAC) 是表观遗传学中开发抗癌药物的有效靶点。在发现具有抗癌效力的新型 HDAC 抑制剂时，5-氯-4-((取代的苯基)氨基)嘧啶片段作为帽基组装到 HDAC 抑制剂的结构中。SAR显示小基团的存在（例如甲氧基取代）有利于HDAC抑制活性。在酶抑制选择性测试中，化合物L20表现出 I 类选择性，对 HDAC1 的 IC 50值为 0.684 µM（选择性指数 >1462）、2.548 µM（选择性指数 >392）和 0.217 µM（选择性指数 >4608） , HDAC2 和 HDAC3 与针对 HDAC6 的效力比较 (IC 50值 > 1000 µM），分别。在抗增殖试验中，化合物L20显示出血液学和实体癌抑制活性。在流式细胞仪中，L20促进了K562细胞的G0/G1期细胞周期阻滞和凋亡。

  DOI：

  10.1080/14756366.2022.2097446

文献信息

• Design, Synthesis, and Anaplastic Lymphoma Kinase (ALK) Inhibitory Activity for a Novel Series of 2,4,8,22-Tetraazatetracyclo[14.3.1.1^3,7.1^9,13]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene Macrocycles
  作者：Henry J. Breslin、Brandon M. Lane、Gregory R. Ott、Arup K. Ghose、Thelma S. Angeles、Mark S. Albom、Mangeng Cheng、Weihua Wan、R. Curtis Haltiwanger、Kevin J. Wells-Knecht、Bruce D. Dorsey

  DOI：10.1021/jm201333e

  日期：2012.1.12

  A novel set of 2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles were prepared as potential anaplastic lymphoma kinase (ALK) inhibitors, designed to rigidly lock an energy-minimized bioactive conformation of the diaminopyrimidine (DAP) scaffold, a well-documented kinase platform. From 13 analogues prepared, macrocycle 2m showed the most promising in vitro ALK enzymatic (IC50 = 0.5 nM) and cellular (IC50 = 10 nM) activities. In addition, macrocycle 2m exhibited a favorable kinase selectivity preference for inhibition of ALK relative to the highly homologous insulin receptor (IR) kinase (IR/ALK ratio of 173). The inclusive in vitro biological results for this set of macrocycles validate this scaffold as a viable kinase template and further corroborate recent DAP/ALK solid state studies indicating that the inverted "U" shaped conformation of the acyclic DAPs is a preferred bioactive conformation.
• Discovery and SAR analysis of 5-chloro-4-((substituted phenyl)amino)pyrimidine bearing histone deacetylase inhibitors
  作者：Lin Zhang、Yiming Chen、Fahui Li、Lihui Zhang、Jinhong Feng、Lei Zhang

  DOI：10.1080/14756366.2022.2097446

  日期：2022.12.31

  Abstract Histone deacetylases (HDACs) are validated targets for the development of anticancer drugs in epigenetics. In the discovery of novel HDAC inhibitors with anticancer potency, the 5-chloro-4-((substituted phenyl)amino)pyrimidine fragment is assembled as a cap group into the structure of HDAC inhibitors. The SAR revealed that presence of small groups (such as methoxy substitution) is beneficial

  摘要 组蛋白去乙酰化酶 (HDAC) 是表观遗传学中开发抗癌药物的有效靶点。在发现具有抗癌效力的新型 HDAC 抑制剂时，5-氯-4-((取代的苯基)氨基)嘧啶片段作为帽基组装到 HDAC 抑制剂的结构中。SAR显示小基团的存在（例如甲氧基取代）有利于HDAC抑制活性。在酶抑制选择性测试中，化合物L20表现出 I 类选择性，对 HDAC1 的 IC 50值为 0.684 µM（选择性指数 >1462）、2.548 µM（选择性指数 >392）和 0.217 µM（选择性指数 >4608） , HDAC2 和 HDAC3 与针对 HDAC6 的效力比较 (IC 50值 > 1000 µM），分别。在抗增殖试验中，化合物L20显示出血液学和实体癌抑制活性。在流式细胞仪中，L20促进了K562细胞的G0/G1期细胞周期阻滞和凋亡。