8-amino-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methylamide

• 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-amino-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methylamide
• 英文别名: 8-amino-N,1,4,4-tetramethyl-5H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 化学式: C₁₄H₁₈N₆O
• 分子量: 286.337
• InChiKey: APPMJHDOPYYSMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-amino-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methylamide 在 cesium iodide 、 亚硝酸异戊酯 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 22.0h， 以35%的产率得到8-iodo-N,1,4,4-tetramethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  [EN] PYRAZOLO-QUINAZOLINE DERIVATIVES,PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  [FR] DERIVES DE PYRAZOLO-QUINAZOLINE, PROCEDE DE PREPARATION ASSOCIE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开了配方(Ia)或(Ib)中定义的吡唑喹唑啉衍生物及其药用盐，其制备方法以及包含它们的药物组合物；本发明的化合物可能在治疗中对与异常蛋白激酶活性相关的疾病，如癌症，具有用处。

  公开号：

  WO2004104007A1
• 作为产物：
  描述：

  ethyl 8-amino-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate 在 氢氧化钾 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 、 乙醇 为溶剂， 反应 21.5h， 生成 8-amino-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methylamide
  参考文献：
  名称：

  [EN] PYRAZOLO-QUINAZOLINE DERIVATIVES,PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  [FR] DERIVES DE PYRAZOLO-QUINAZOLINE, PROCEDE DE PREPARATION ASSOCIE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开了配方(Ia)或(Ib)中定义的吡唑喹唑啉衍生物及其药用盐，其制备方法以及包含它们的药物组合物；本发明的化合物可能在治疗中对与异常蛋白激酶活性相关的疾病，如癌症，具有用处。

  公开号：

  WO2004104007A1

文献信息

• [EN] PYRAZOLO-QUINAZOLINE DERIVATIVES AS CHOLINE KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLO-QUINAZOLINE UTILISÉS EN TANT QU'INHIBITEURS DE CHOLINE KINASE
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2019011715A1

  公开（公告）日：2019-01-17

  The present invention relates to substituted pyrazolo-quinazoline derivatives which modulate the activity of Choline Kinase (ChoK). The compounds of this invention are therefore useful in treating diseases caused by an altered choline metabolism, such as cancer, cell proliferative disorders, infectious diseases of different origin, immune- related disorders and neurodegenerative disorders. 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.

  本发明涉及替代吡唑喹唑啉衍生物，其调节胆碱激酶（ChoK）的活性。因此，本发明的化合物在治疗由改变的胆碱代谢引起的疾病方面具有用途，如癌症、细胞增殖异常、不同起源的传染病、免疫相关疾病和神经退行性疾病。本发明还提供了制备这些化合物的方法、包含这些化合物的药物组合物以及利用包含这些化合物的药物组合物治疗疾病的方法。
• Pyrazolo-Quinazoline Derivatives, Process for Their Preparation and Their Use as Kinase Inhibitors
  申请人：Traquandi Gabriella

  公开号：US20090124605A1

  公开（公告）日：2009-05-14

  Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, 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 disregulated protein kinase activity, like cancer.

  本发明公开了式(Ia)或(Ib)的吡唑喹唑啉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；本发明的化合物在治疗与蛋白激酶活性失调有关的疾病，如癌症中可能有用。
• Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors
  申请人：Traquandi Gabriella

  公开号：US20070185143A1

  公开（公告）日：2007-08-09

  Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention maybe useful in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer”.

  本发明公开了公式（Ia）或（Ib）中定义的吡唑并[3,4-d]喹唑啉衍生物及其药学上可接受的盐，其制备方法和包含它们的制药组合物；本发明中的化合物可能在治疗中有用，用于治疗与蛋白激酶活性失调有关的疾病，如癌症。
• PYRAZOLO-QUINAZOLINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  申请人：Traquandi Gabriella

  公开号：US20130338148A1

  公开（公告）日：2013-12-19

  Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, 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 disregulated protein kinase activity, like cancer.

  本发明揭示了式(Ia)或(Ib)的吡唑并喹唑啉衍生物及其药学上可接受的盐，以及它们的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，如癌症方面有用。
• Substituted pyrazolo[4,3-h]quinazolines as choline kinase inhibitors
  申请人：NERVIANO MEDICAL SCIENCES S.R.L.

  公开号：US11117901B2

  公开（公告）日：2021-09-14

  The present invention relates to substituted pyrazolo-quinazoline derivatives which modulate the activity of Choline Kinase (ChoK). The compounds of this invention are therefore useful in treating diseases caused by an altered choline metabolism, such as cancer, cell proliferative disorders, infectious diseases of different origin, immune-related disorders and neurodegenerative disorders. 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. The compounds of this disclosure include those of formula (I):

  本发明涉及可调节胆碱激酶（ChoK）活性的取代吡唑-喹唑啉衍生物。因此，本发明的化合物可用于治疗由胆碱代谢改变引起的疾病，如癌症、细胞增殖性疾病、不同来源的传染性疾病、免疫相关疾病和神经退行性疾病。本发明还提供了制备这些化合物的方法、包含这些化合物的药物组合物，以及利用包含这些化合物的药物组合物治疗疾病的方法。本发明公开的化合物包括式（I）化合物：