5-(2-amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid ethyl ester | 1137468-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-(2-amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 5-(2-aminopyrimidin-4-yl)-1H-pyrrole-3-carboxylate
• CAS: 1137468-07-5
• 化学式: C₁₁H₁₂N₄O₂
• 分子量: 232.242
• InChiKey: GVOLFIGFKIDLFI-UHFFFAOYSA-N

物化性质

• 沸点：
  571.7±60.0 °C(Predicted)
• 密度：
  1.318±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2-amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid ethyl ester 在 copper(l) iodide 、 1-羟基-1H-苯并三唑铵盐 、 palladium diacetate 、 sodium hydride 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium hydroxide 、 cesium iodide 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 5-[2-(5-bromo-2-trifluoromethoxyphenylamino)pyrimidin-4-yl]-1-methyl-1H-pyrrole-3-carboxylic acid amide
  参考文献：
  名称：

  5-(2-Amino-pyrimidin-4-yl)-1H-pyrrole and 2-(2-amino-pyrimidin-4-yl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one derivatives as new classes of selective and orally available Polo-like kinase 1 inhibitors

  摘要：

  The discovery and characterization of two new chemical classes of potent and selective Polo-like kinase 1 (PLK1) inhibitors is reported. For the most interesting compounds, we discuss the biological activities, crystal structures and preliminary pharmacokinetic parameters. The more advanced compounds inhibit PLK1 in the enzymatic assay at the nM level and exhibit good activity in cell proliferation on A2780 cells. Furthermore, these compounds showed high levels of selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3 isoforms. Additionally, the compounds show acceptable oral bioavailability in mice making these inhibitors suitable candidates for further in vivo activity studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.065
• 作为产物：
  描述：

  5-(2-aminopyrimidin-4-yl)-2-chloro-1H-pyrrole-3-carboxylic acid ethyl ester hydrochloride 在 palladium 10% on activated carbon 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以50%的产率得到5-(2-amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRROLO-PYRIMIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  [FR] DÉRIVÉS DE PYRROLOPYRIMIDINE SUBSTITUÉS, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开了公式（I）的取代吡咯-嘧啶衍生物及其药用盐，如规范中定义的，以及它们的制备方法和包含它们的药物组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病，如癌症中有用。

  公开号：

  WO2009040399A1

文献信息

• [EN] N-ARYL-2-(2-ARYLAMINOPYRIMIDIN-4-YL)PYRROL-4-CARBOXAMIDE DERIVATIVES AS MPS1 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE N-ARYL-2-(2-ARYLAMINOPYRIMIDIN-4-YL)PYRROL-4-CARBOXAMIDE À TITRE D'INHIBITEURS DE KINASE MPS1
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2010108921A1

  公开（公告）日：2010-09-30

  The present invention relates to substituted pyrrolyl-pyrimidines which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

  本发明涉及替代吡咯基嘧啶，其调节蛋白激酶活性，因此在治疗由失调的蛋白激酶活性引起的疾病方面具有用处，特别是MPS1。本发明还提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用这些化合物或含有它们的药物组合物治疗疾病的方法。
• N-ARYL-2-(2-ARYLAMINOPYRIMIDIN-4-YL)PYRROL-4-CARBOXAMIDE DERIVATIVES AS MPS1 KINASE INHIBITORS
  申请人：Caldarelli Marina

  公开号：US20120065192A1

  公开（公告）日：2012-03-15

  The present invention relates to substituted pyrrolyl-pyrimidines which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

  本发明涉及取代的吡咯基嘧啶，其调节蛋白激酶活性，因此在治疗由失调的蛋白激酶活性引起的疾病，特别是MPS1方面有用。本发明还提供了制备这些化合物的方法，包括这些化合物的制药组合物，以及利用这些化合物或含有它们的制药组合物治疗疾病的方法。
• Substituted Pyrrolo-Pyrimidine Derivatives, Process for Their Preparation and Their Use as Kinase Inhibitors
  申请人：Caruso Michele

  公开号：US20120122882A1

  公开（公告）日：2012-05-17

  Substituted pyrrolo-pyrimidine derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer.

  本文披露了公式(I)的取代嘧啶-吡咯衍生物及其药学上可接受的盐，以及其制备方法和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病，如癌症方面具有用途。
• N-aryl-2-(2-arylaminopyrimidin-4-yl)pyrrol-4-carboxamide derivatives as MPS1 kinase inhibitors
  申请人：Caldarelli Marina

  公开号：US08772280B2

  公开（公告）日：2014-07-08

  The present invention relates to substituted pyrrolyl-pyrimidines which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

  本发明涉及替代吡咯基嘧啶，其调节蛋白激酶活性，因此在治疗由失调的蛋白激酶活性引起的疾病，特别是MPS1方面具有用途。本发明还提供了制备这些化合物的方法，包含这些化合物的制药组合物以及利用这些化合物或含有它们的制药组合物治疗疾病的方法。
• Substituted pyrrolo-pyrimidine derivatives, process for their preparation and their use as kinase inhibitors
  申请人：Caruso Michele

  公开号：US08426417B2

  公开（公告）日：2013-04-23

  Substituted pyrrolo-pyrimidine derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer.

  本发明公开了公式（I）的替代吡咯-嘧啶衍生物及其药学上可接受的盐，其定义在说明书中，以及制备它们的过程和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病（如癌症）中有用。