(2,5-dichloropyrimidin-4-yl)-3-vinylphenylamine | 1192471-59-2

• 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: (2,5-dichloropyrimidin-4-yl)-3-vinylphenylamine
• 英文别名: 2,5-dichloro-N-(3-ethenylphenyl)pyrimidin-4-amine
• CAS: 1192471-59-2
• 化学式: C₁₂H₉Cl₂N₃
• 分子量: 266.13
• InChiKey: DXNUAKREMDNXDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  (2,5-dichloropyrimidin-4-yl)-3-vinylphenylamine 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 8.5h， 生成 (14Z)-6-chloro-17-(4-methylpiperazin-1-yl)-19-methoxy-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,14,16,18-decaene
  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：

  3-乙烯基苯胺 、 2,4,5-三氯嘧啶 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以87%的产率得到(2,5-dichloropyrimidin-4-yl)-3-vinylphenylamine
  参考文献：
  名称：

  [EN] MACROCYCLIC COMPOUNDS AS ALK, FAK AND JAK2 INHIBITORS
  [FR] COMPOSÉS MACROCYLCIQUES COMME INHIBITEURS D'ALK, DE FAK ET DE JAK2

  摘要：

  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。

  公开号：

  WO2012125603A1

文献信息

• MACROCYCLIC COMPOUNDS AND THEIR USE AS KINASE INHIBITORS
  申请人：Combs Andrew Paul

  公开号：US20090286778A1

  公开（公告）日：2009-11-19

  The present invention relates to macrocyclic compounds of Formula I: or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK/ALK inhibitors useful in the treatment of JAK/ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

  本发明涉及以下化学式I的大环化合物： 或其药用可接受盐或季铵盐，其中所述成员在此提供，并且它们的组成物和使用方法，这些JAK/ALK抑制剂在治疗JAK/ALK相关疾病中有用，例如炎症和自身免疫性疾病以及癌症。
• [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。
• US8871753B2
  申请人：——

  公开号：US8871753B2

  公开（公告）日：2014-10-28
• [EN] MACROCYCLIC COMPOUNDS AND THEIR USE AS KINASE INHIBITORS<br/>[FR] COMPOSÉS MACROCYCLIQUES ET LEUR UTILISATION À TITRE D'INHIBITEURS DE KINASE
  申请人：INCYTE CORP

  公开号：WO2009132202A2

  公开（公告）日：2009-10-29

  The present invention relates to macrocyclic compounds of Formula I: or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK/ ALK inhibitors useful in the treatment of JAK/ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
• 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.