5-{4-[(Pyridin-2-ylmethyl)-amino]-5-trifluoromethyl-pyrimidin-2-ylamino}-1,3-dihydro-indol-2-one | 717906-37-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-{4-[(Pyridin-2-ylmethyl)-amino]-5-trifluoromethyl-pyrimidin-2-ylamino}-1,3-dihydro-indol-2-one
• 英文别名: 5-(4-(Pyridin-2-ylmethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)indolin-2-one；5-[[4-(pyridin-2-ylmethylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-1,3-dihydroindol-2-one
• CAS: 717906-37-1
• 化学式: C₁₉H₁₅F₃N₆O
• 分子量: 400.363
• InChiKey: DAJMEJBPGNBYEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  91.8
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氨甲基吡啶 、 5-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-2,3-dihydro-1H-indol-2-one 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-{4-[(Pyridin-2-ylmethyl)-amino]-5-trifluoromethyl-pyrimidin-2-ylamino}-1,3-dihydro-indol-2-one
  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。
• Compound for the treatment of abnormal cell growth
  申请人：Pfizer Inc

  公开号：US20040220177A1

  公开（公告）日：2004-11-04

  The invention relates to compounds of the formula 1 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , n, A and B are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.

  本发明涉及公式11的化合物，以及其药物可接受的盐、前药和溶剂化物，其中R1、R2、R3、R4、R5、n、A和B的定义如本文所述。本发明还涉及通过给予公式1的化合物治疗哺乳动物异常细胞生长的方法，并涉及用于治疗此类疾病的制药组合物，其中包含公式1的化合物。本发明还涉及制备公式1的化合物的方法。
• 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。