N2-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N4-(2-methoxy-5-vinylphenyl)pyrimidine-2,4-diamine | 1352244-31-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N2-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N4-(2-methoxy-5-vinylphenyl)pyrimidine-2,4-diamine
• 英文别名: N(2)-[3-Bromo-4-(4-methyl-piperazin-1-yl)-phenyl]-5-chloro-N(4)-(2-methoxy-5-vinyl-phenyl)-pyrimidine-2,4-diamine；2-N-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-4-N-(5-ethenyl-2-methoxyphenyl)pyrimidine-2,4-diamine
• CAS: 1352244-31-5
• 化学式: C₂₄H₂₆BrClN₆O
• 分子量: 529.867
• InChiKey: HGLYQZMIGLBWRC-UHFFFAOYSA-N

物化性质

• 沸点：
  659.1±65.0 °C(Predicted)
• 密度：
  1.434±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N2-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N4-(2-methoxy-5-vinylphenyl)pyrimidine-2,4-diamine 在 吡啶 、 palladium diacetate 、 potassium diazodicarboxylate 、 溶剂黄146 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 120.5h， 生成 6-chloro-10-methoxy-17-(4-methylpiperazin-1-yl)-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 trifluoroacetate (1:1)
  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：

  1-(2-bromo-4-nitrophenyl)-4-methylpiperazine 在 盐酸 、 一水合肼 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 叔丁醇 为溶剂， 反应 145.0h， 生成 N2-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N4-(2-methoxy-5-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
• 作为试剂：
  描述：

  N4-[5-bromo-2-(propane-2-sulfonyl)phenyl]-5-chloro-N2-[4-(4-methylpiperazin-1-yl)-3-vinylphenyl]pyrimidine-2,4-diamine 、 4-(4-methylpiperazin-1-yl)-3-vinylaniline 、 [5-bromo-2-(propane-2-sulfonyl)phenyl]-(2,5-dichloropyrimidin-4-yl)amine 、 乙二醇二甲醚 在 N2-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N4-(2-methoxy-5-vinylphenyl)pyrimidine-2,4-diamine 、 乙酸乙酯 、 碳酸氢钠 、 Sodium sulfate-III 作用下， 以 叔丁醇 、 乙二醇甲醚 为溶剂， 反应 144.0h， 以to give desired N(2)-[3-Bromo-4-(4-methyl-piperazin-1-yl)-phenyl]-5-chloro-N(4)-(2-methoxy-5-vinyl-phenyl)-pyrimidine-2,4-diamine in 20% yield的产率得到N2-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N4-(2-methoxy-5-vinylphenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Macrocyclic Compounds as ALK, FAK and JAK2 Inhibitors

  摘要：

  本发明提供了I式化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A和X的定义如本文所述，以及其治疗方法和用途。

  公开号：

  US20140031351A1

文献信息

• [EN] MACROCYCLIC COMPOUNDS AS ALK, FAK AND JAK2 INHIBITORS<br/>[FR] COMPOSÉS MACROCYLCIQUES COMME INHIBITEURS D'ALK, DE FAK ET DE JAK2
  申请人：CEPHALON INC

  公开号：WO2012125603A1

  公开（公告）日：2012-09-20

  The present invention provides compounds of Formula I or a pharmaceutically acceptable salt forms thereof, wherein R1, R2, R3, R4, R5, A and X are as defined herein, methods of treatment and uses thereof.

  本发明提供了式I的化合物或其药用可接受的盐形式，其中R1、R2、R3、R4、R5、A和X如本文所定义，以及其治疗方法和用途。
• MACROCYCLIC COMPOUNDS AS ALK, FAK AND JAK2 INHIBITORS
  申请人：Cephalon, Inc.

  公开号：EP2686323A1

  公开（公告）日：2014-01-22
• US9487529B2
  申请人：——

  公开号：US9487529B2

  公开（公告）日：2016-11-08