8-[(2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid | 1202056-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-[(2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid
• 英文别名: 8-(2-Methoxyanilino)-1-methyl-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxylic acid
• CAS: 1202056-99-2
• 化学式: C₁₈H₁₇N₅O₃
• 分子量: 351.365
• InChiKey: HADUZSIVCXLYDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-[(2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid 在 氨 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 8-[(2-methoxyphenyl)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：

  ethyl 8-iodo-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate 在 乙醇 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 8-[(2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid
  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

• 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 AS PROTEIN KINASE ACTIVITY MODULATORS
  申请人：Les Laboratoires Servier

  公开号：EP2303891B1

  公开（公告）日：2016-02-17
• US8846701B2
  申请人：——

  公开号：US8846701B2

  公开（公告）日：2014-09-30
• Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors
  作者：Marina Caldarelli、Mauro Angiolini、Teresa Disingrini、Daniele Donati、Marco Guanci、Stefano Nuvoloni、Helena Posteri、Francesca Quartieri、Marco Silvagni、Riccardo Colombo

  DOI：10.1016/j.bmcl.2011.05.122

  日期：2011.8

  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.