N-甲基-N-[2-[[[2-[(2-氧代-2,3-二氢-1H-吲哚-5-基)氨基]-5-三氟甲基嘧啶-4-基]氨基]甲基]苯基]甲磺酰胺 | 717906-29-1

• 物质功能分类: 生物化工 - 抑制剂 - 血管生成(Angiogenesis)
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-甲基-N-[2-[[[2-[(2-氧代-2,3-二氢-1H-吲哚-5-基)氨基]-5-三氟甲基嘧啶-4-基]氨基]甲基]苯基]甲磺酰胺
• 英文名称: PF-431396
• 英文别名: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-YL)amino]-5-trifluoromethylpyrimidin-4-YL]amino]methyl]phenyl]methanesulfonamide；N-methyl-N-[2-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide
• CAS: 717906-29-1
• 化学式: C₂₂H₂₁F₃N₆O₃S
• 分子量: 506.508
• InChiKey: POJZIZBONPAWIV-UHFFFAOYSA-N

物化性质

• 密度：
  1.506
• 溶解度：
  二甲基亚砜：≥10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  11

安全信息

• 危险品标志：
  T
• 安全说明：
  S26,S45
• 危险类别码：
  R25,R36
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

PF-431396是双PYK2/FAK抑制剂，IC50分别为11 nM和2 nM。

体外研究

在A20细胞中，PF-431396阻断抗Ig-和聚集的LFA-1诱导的Pyk2与FAK的酪氨酸磷酸化，并进一步抑制B细胞扩散。此外，它还连续抑制增钙缺乏以及钙存在下W-7诱导的蛋白质酪氨酸磷酸化（PY）。

靶点

Target	Value
FAK	2 nM
PYK2	11 nM

反应信息

• 作为产物：
  描述：

  5-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-2,3-dihydro-1H-indol-2-one 、 N-[2-(氨基甲基)苯基]-n-甲基甲烷磺酰胺 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-甲基-N-[2-[[[2-[(2-氧代-2,3-二氢-1H-吲哚-5-基)氨基]-5-三氟甲基嘧啶-4-基]氨基]甲基]苯基]甲磺酰胺
  参考文献：
  名称：

  Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): Structure–activity relationships and strategies for the elimination of reactive metabolite formation

  摘要：

  The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.

  DOI：

  10.1016/j.bmcl.2008.10.030

文献信息

• Pyrimidine derivatives for the treatment of abnormal cell growth
  申请人：Kath Charles John

  公开号：US20050256145A1

  公开（公告）日：2005-11-17

  The present invention relates to a compound of the formula 1 wherein R 1 -R 4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及一种化合物，其化学式为1，其中R1-R4如本文所定义。这种新颖的嘧啶衍生物在哺乳动物中用于治疗异常细胞增长，如癌症。本发明还涉及一种在哺乳动物中，特别是人类中使用这种化合物治疗异常细胞增长的方法，以及含有这种化合物的药物组合物。
• [EN] PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH<br/>[FR] DERIVES DE PYRIMIDINE POUR LE TRAITEMENT DE LA CROISSANCE CELLULAIRE ANORMALE
  申请人：PFIZER PROD INC

  公开号：WO2005111023A1

  公开（公告）日：2005-11-24

  The present invention relates to a compound of the formula (I) wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及式（I）的化合物，其中R1-R4如本文所定义。这种新型嘧啶衍生物在哺乳动物中治疗异常细胞增长，如癌症等方面非常有用。本发明还涉及使用这种化合物治疗哺乳动物（特别是人类）中的异常细胞增长的方法，以及含有这种化合物的制药组合物。
• [EN] PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH<br/>[FR] DERIVES DE PYRIMIDINE DESTINES AU TRAITEMENT DE LA CROISSANCE CELLULAIRE ANORMALE
  申请人：PFIZER PROD INC

  公开号：WO2004056807A1

  公开（公告）日：2004-07-08

  The present invention relates to a compound of the formula (I), wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in thetreatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及一种化合物，其化学式为（I），其中R1-R4的定义如本文所述。这种新型嘧啶衍生物在哺乳动物中治疗异常细胞生长，如癌症等方面有用。本发明还涉及一种使用这种化合物治疗哺乳动物中异常细胞生长的方法，特别是人类，并且涉及含有这种化合物的制药组合物。
• PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
  申请人：KATH JOHN CHARLES

  公开号：US20080182840A1

  公开（公告）日：2008-07-31

  The present invention relates to a compound of the formula 1 wherein R 1 -R 4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及式1的化合物，其中R1-R4如本文所定义。这些新型嘧啶衍生物在哺乳动物中治疗异常细胞生长，如癌症方面具有用途。本发明还涉及使用这些化合物治疗哺乳动物，特别是人类异常细胞生长的方法，以及含有这些化合物的制药组合物。
• FAK INHIBITORS
  申请人：Cancer Therapeutics CRC PTY LTD.

  公开号：US20150231135A1

  公开（公告）日：2015-08-20

  A compound of the formula (I): where R 1 or R 2 is a cyclic amine group and R 5 is an aromatic group with a carbonyl containing substituent for use as a FAK inhibitor.

  一种化合物，其化学式为(I)：其中R1或R2为环状胺基团，R5为含有羰基取代基的芳香基团，用作FAK抑制剂。