2-chloro-4-(3-chloro-4-fluorophenyl)-5-methylpyrimidine | 1341200-62-1

• 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: 2-chloro-4-(3-chloro-4-fluorophenyl)-5-methylpyrimidine
• 英文别名: 2-Chloro-4-(3-chloro-4-fluorophenyl)-5-methylpyrimidine
• CAS: 1341200-62-1
• 化学式: C₁₁H₇Cl₂FN₂
• 分子量: 257.094
• InChiKey: WAVRNJYACGPQIP-UHFFFAOYSA-N

物化性质

• 沸点：
  385.3±37.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-氟-4-(4-甲基-1-哌嗪基)苯胺 、 2-chloro-4-(3-chloro-4-fluorophenyl)-5-methylpyrimidine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 叔丁醇 为溶剂， 反应 12.0h， 以73%的产率得到4-(3-chloro-4-fluorophenyl)-N-(3-fluoro-4-(4-methylpiperazin-1-yl)phenyl)-5-methylpyrimidin-2-amine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors

  摘要：

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

  DOI：

  10.1021/ml200198x
• 作为产物：
  描述：

  2,4-二氯-5-甲基嘧啶 、 3-氯-4-氟苯硼酸 在 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以70%的产率得到2-chloro-4-(3-chloro-4-fluorophenyl)-5-methylpyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors

  摘要：

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

  DOI：

  10.1021/ml200198x

文献信息

• [EN] SUBSTITUTED N-PHENYLPYRIMIDIN-2-AMINE ANALOGS AS INHIBITORS OF THE AXL KINASE<br/>[FR] ANALOGUES DE N-PHÉNYLPYRIMIDINE-2-AMINE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'AXL KINASE
  申请人：UNIV UTAH RES FOUND

  公开号：WO2012135800A1

  公开（公告）日：2012-10-04

  In one aspect, the invention relates to substituted N-phenylpyrimidin-2-amine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of Axl kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the Axl kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  该发明涉及替代的N-苯基嘧啶-2-胺类似物、其衍生物和相关化合物，它们可作为Axl激酶的抑制剂；合成这些化合物的方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与Axl激酶功能障碍相关的疾病的方法。本文摘要旨在作为在特定领域搜索的工具，并不意味着对本发明的限制。
• SUBSTITUTED N-PHENYLPYRIMIDIN-2-AMINE ANALOGS AS INHIBITORS OF THE AXL KINASE
  申请人：Bearss David J.

  公开号：US20120283261A1

  公开（公告）日：2012-11-08

  In one aspect, the invention relates to substituted N-phenylpyrimidin-2-amine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of Axl kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the Axl kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  该发明涉及取代的N-苯基嘧啶-2-胺类似物、其衍生物和相关化合物，这些化合物可用作Axl激酶的抑制剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与Axl激酶功能障碍相关的疾病的方法。本摘要旨在作为特定领域搜索的扫描工具，不限制本发明。
• Substituted N-phenylpyrimidin-2-amine analogs as inhibitors of the Axl kinase
  申请人：Bearss David J.

  公开号：US08901120B2

  公开（公告）日：2014-12-02

  In one aspect, the invention relates to substituted N-phenylpyrimidin-2-amine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of Axl kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the Axl kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及替代N-苯基嘧啶-2-胺类似物、其衍生物及相关化合物，这些化合物可用作Axl激酶的抑制剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及利用这些化合物和组合物治疗与Axl激酶功能失调相关的疾病的方法。本文摘要旨在作为搜索特定领域的工具，不旨在限制本发明。
• US8901120B2
  申请人：——

  公开号：US8901120B2

  公开（公告）日：2014-12-02
• Design, Synthesis, and Biological Evaluation of a Series of Novel AXL Kinase Inhibitors
  作者：Alexis Mollard、Steven L. Warner、Lee T. Call、Mark L. Wade、Jared J. Bearss、Anupam Verma、Sunil Sharma、Hariprasad Vankayalapati、David J. Bearss

  DOI：10.1021/ml200198x

  日期：2011.12.8

  The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC(50) = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.