tert-butyl 4-({3-[(2,6-diethylphenyl)carbamoyl]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl}amino)-3-methoxybenzoate | 1202055-50-2

• 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: tert-butyl 4-({3-[(2,6-diethylphenyl)carbamoyl]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl}amino)-3-methoxybenzoate
• 英文别名: tert-butyl 4-[[3-[(2,6-diethylphenyl)carbamoyl]-1-methyl-4,5-dihydropyrazolo[4,3-h]quinazolin-8-yl]amino]-3-methoxybenzoate
• CAS: 1202055-50-2
• 化学式: C₃₃H₃₈N₆O₄
• 分子量: 582.703
• InChiKey: XTHFCLZGGOAZSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-({3-[(2,6-diethylphenyl)carbamoyl]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl}amino)-3-methoxybenzoate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-(2,6-diethylphenyl)-8-[(2-methoxy-4-{[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]carbonyl}phenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors

  摘要：

  The synthesis and SAR of a series of novel pyrazolo-quinazolines as potent and selective MPS1 inhibitors are reported. We describe the optimization of the initial hit, identified by screening the internal library collection, into an orally available, potent and selective MPS1 inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.122
• 作为产物：
  描述：

  2,6-二乙基苯胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hexamethyldisilazane 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 12.17h， 生成 tert-butyl 4-({3-[(2,6-diethylphenyl)carbamoyl]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl}amino)-3-methoxybenzoate
  参考文献：
  名称：

  Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors

  摘要：

  The synthesis and SAR of a series of novel pyrazolo-quinazolines as potent and selective MPS1 inhibitors are reported. We describe the optimization of the initial hit, identified by screening the internal library collection, into an orally available, potent and selective MPS1 inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.122

文献信息

• [EN] PYRAZOLO-QUINAZOLINES<br/>[FR] PYRAZOLO-QUINAZOLINES
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2009156315A1

  公开（公告）日：2009-12-30

  The present invention relates to pyrazolo-quinazolines, characterized by an ortho-substituted-arylamino, heterocyclylamino- or C3-C7 cycloalkylamino residue at 8 position and an aryl, heterocyclyl or C3-C7 cycloalkyl as substituent of a carboxamide at 3 position of the molecula framework. The compounds of this invention modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1/TTK. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

  本发明涉及吡唑喹唑啉类化合物，其特征在于在分子骨架的8位具有一个邻位取代的芳基氨基、杂环氨基或C3-C7环烷基氨基残基，以及在3位的羧酰胺上有一个芳基、杂环基或C3-C7环烷基作为取代基。本发明的化合物调节蛋白激酶的活性，因此在治疗由蛋白激酶活性失调引起的疾病中特别有用，尤其是MPS1/TTK。本发明还提供了制备这些化合物的方法，包括含有这些化合物的药物组合物以及利用含有这些化合物的药物组合物治疗疾病的方法。
• PYRAZOLO--QUINAZOLINES
  申请人：Caldareli Marina

  公开号：US20110105542A1

  公开（公告）日：2011-05-05

  The present invention relates to pyrazolo-quinazolines, characterized by an ortho-substituted-arylamino, heterocyclylamino- or C 3 -C 7 cycloalkylamino residue at 8 position and an aryl, heterocyclyl or C 3 -C 7 cycloalkyl as substituent of a carboxamide at 3 position of the molecula framework. The compounds of this invention modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1/TTK. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

  本发明涉及吡唑并喹唑啉，其特征在于在分子框架的8位具有一个邻位取代的芳基氨基，杂环基氨基或C3-C7环烷基氨基残基，并在3位上的羧酰胺上具有芳基，杂环基或C3-C7环烷基的取代基。本发明的化合物调节蛋白激酶的活性，因此在治疗由失调的蛋白激酶活性引起的疾病，特别是MPS1/TTK方面具有用途。本发明还提供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包含这些化合物的制药组合物治疗疾病的方法。
• Pyrazolo-quinazolines
  申请人：Caldarelli Marina

  公开号：US08846701B2

  公开（公告）日：2014-09-30

  The present invention relates to pyrazolo-quinazolines, characterized by an ortho-substituted-arylamino, heterocyclylamino- or C3-C7 cycloalkylamino residue at 8 position and an aryl, heterocyclyl or C3-C7 cycloalkyl as substituent of a carboxamide at 3 position of the molecule framework. The compounds of this invention modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular MPS1/TTK. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

  本发明涉及吡唑并喹唑啉，其特征在于8位具有取代基的芳胺基、杂环胺基或C3-C7环烷基胺基，3位的分子框架上的羧酰胺基取代基为芳基、杂环基或C3-C7环烷基。本发明的化合物调节蛋白激酶的活性，因此在治疗由失调的蛋白激酶活性引起的疾病，特别是MPS1/TTK方面具有用途。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的制药组合物治疗疾病的方法。
• PYRAZOLO-QUINAZOLINES
  申请人：Nerviano Medical Sciences S.r.l.

  公开号：EP2303891A1

  公开（公告）日：2011-04-06
• PYRAZOLO-QUINAZOLINES AS PROTEIN KINASE ACTIVITY MODULATORS
  申请人：Les Laboratoires Servier

  公开号：EP2303891B1

  公开（公告）日：2016-02-17