5-bromo-N'-(5-cyclopropyl-2H-pyrazol-3-yl)-N-[(1S)-1-(4-fluorophenyl)ethyl]pyrimidine-2,4-diamine

• 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: 5-bromo-N'-(5-cyclopropyl-2H-pyrazol-3-yl)-N-[(1S)-1-(4-fluorophenyl)ethyl]pyrimidine-2,4-diamine
• 英文别名: 5-bromo-N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-[(1S)-1-(4-fluorophenyl)ethyl]pyrimidine-2,4-diamine；5-bromo-4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-N-[(1S)-1-(4-fluorophenyl)ethyl]pyrimidine-2,4-diamine
• 化学式: C₁₈H₁₈BrFN₆
• 分子量: 417.284
• InChiKey: BJULBAQIZYUYFI-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  78.5
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-bromo-N'-(5-cyclopropyl-2H-pyrazol-3-yl)-N-[(1S)-1-(4-fluorophenyl)ethyl]pyrimidine-2,4-diamine 、 氰化亚铜 以 喹啉 为溶剂， 反应 5.0h， 以gave the desired product as a solid (67 mg, 30%)的产率得到4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2-{[(1S)-1-(4-fluorophenyl)ethyl]amino}pyrimidine-5-carbonitrile
  参考文献：
  名称：

  PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSINE KINASES

  摘要：

  描述了式(I)的化合物及其在抑制Trk活性方面的应用。

  公开号：

  US20100152219A1
• 作为产物：
  描述：

  5-bromo-2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine 、 (S)-(-)-1-(4-氟苯基)乙胺 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 生成 5-bromo-N'-(5-cyclopropyl-2H-pyrazol-3-yl)-N-[(1S)-1-(4-fluorophenyl)ethyl]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Identification of 4-Aminopyrazolylpyrimidines as Potent Inhibitors of Trk Kinases

  摘要：

  The design, synthesis and biological evaluation of a series of 4-aminopyrazolylpyrimidines as potent Trk kinase inhibitors is reported. High-throughput screening identified a promising hit in the 4-aminopyrazolylpyrimidine chemotype. Initial optimization of the series led to more potent Trk inhibitors. Further optimization using two strategies resulted in significant improvement of physical properties and led to the discovery of IN (AZ-23), a potent, orally bioavailable Trk A/B inhibitor. The compound offers the potential to test the hypothesis that modulation of Trk activity will be of benefit in the treatment of cancer and other indications in vivo.

  DOI：

  10.1021/jm800343j

文献信息

• [EN] PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES<br/>[FR] DERIVES DE PYRAZOLE EN TANT QU'INHIBITEURS DE RECEPTEUR TYROSINE KINASES
  申请人：ASTRAZENECA AB

  公开号：WO2005049033A1

  公开（公告）日：2005-06-02

  Compounds of formula (I): and their use in the inhibition of Trk activity are described.

  化合物的化学式（I）及其在抑制Trk活性中的应用被描述。
• Pyrazole derivatives as inhibitors of receptor tyrosone kinases
  申请人：Block Howard Michael

  公开号：US20070142413A1

  公开（公告）日：2007-06-21

  Compounds of formula (I): and their use in the inhibition of Trk activity are described.

  描述了式(I)的化合物及其在抑制Trk活性方面的用途。
• Point mutations in TRK inhibitor-resistant cancer and methods relating to the same
  申请人：Loxo Oncology, Inc.

  公开号：US10370727B2

  公开（公告）日：2019-08-06

  Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

  本文提供了治疗癌症受试者的方法、为癌症受试者选择治疗方法的方法、为不包括Trk抑制剂的治疗方法选择癌症受试者的方法、确定癌症受试者对Trk抑制剂治疗产生阳性反应的可能性的方法、预测Trk抑制剂对癌症受试者疗效的方法、确定受试者罹患Trk抑制剂抗性癌症风险的方法，以及根据从受试者样本中检测到的细胞具有NTRK1和/或NTRK2和/或NTRK3中至少一种点突变，确定受试者存在Trk抑制剂抗性癌症的方法。
• EP1686999B1
  申请人：——

  公开号：EP1686999B1

  公开（公告）日：2009-07-01
• Use of Pyrazolyl-Pyrimidine Derivatives in the Treatment of Pain
  申请人：Claesson Alf

  公开号：US20090005396A1

  公开（公告）日：2009-01-01

  This invention relates to the use of a pyrazolyl-pyrimidine of the formula (I). n=0, 1, 2 or 3 (I) in the manufacture of a medicament for use in the treatment or prophylaxis of pain. and to their pharmaceutical formulations and to their methods of use.