5-[2-(5-bromo-2-trifluoromethoxyphenylamino)pyrimidin-4-yl]-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester | 1137467-60-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-[2-(5-bromo-2-trifluoromethoxyphenylamino)pyrimidin-4-yl]-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester
• 英文别名: 5-[2-(5-bromo-2-trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester；ethyl 5-[2-[5-bromo-2-(trifluoromethoxy)anilino]pyrimidin-4-yl]-1-methylpyrrole-3-carboxylate
• CAS: 1137467-60-7
• 化学式: C₁₉H₁₆BrF₃N₄O₃
• 分子量: 485.26
• InChiKey: MZRPRLAVSSPYBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-[2-(5-bromo-2-trifluoromethoxyphenylamino)pyrimidin-4-yl]-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 在 tris-(dibenzylideneacetone)dipalladium(0) 、 1-羟基-1H-苯并三唑铵盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium hydroxide 、 lithium hexamethyldisilazane 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 1-methyl-5-{2-[5-(4-methylpiperazin-1-yl)-2-trifluoromethoxyphenylamino]pyrimidin-4-yl}-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-amino-pyrimidin-4-yl)-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 在 copper(l) iodide 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 cesium iodide 、 亚硝酸异戊酯 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 5-[2-(5-bromo-2-trifluoromethoxyphenylamino)pyrimidin-4-yl]-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester
  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

文献信息

• [EN] SUBSTITUTED PYRROLO-PYRIMIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLOPYRIMIDINE SUBSTITUÉS, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2009040399A1

  公开（公告）日：2009-04-02

  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.

  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。
• 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。
• 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。
• SUBSTITUTED PYRROLO-PYRIMIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  申请人：Nerviano Medical Sciences S.r.l.

  公开号：EP2203442B1

  公开（公告）日：2012-06-20
• US8426417B2
  申请人：——

  公开号：US8426417B2

  公开（公告）日：2013-04-23