ethyl 6-[(dimethylamino)methylidene]-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate | 802541-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 6-[(dimethylamino)methylidene]-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate
• 英文别名: ethyl 6-[(dimethylamino)methylene]-7-oxo-1-methyl-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate；ethyl 6-[(dimethylamino)methylene]-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate；ethyl 6-(dimethylaminomethylidene)-1-methyl-7-oxo-4,5-dihydroindazole-3-carboxylate
• CAS: 802541-37-3
• 化学式: C₁₄H₁₉N₃O₃
• 分子量: 277.323
• InChiKey: VYUDULDAVWUAHL-UHFFFAOYSA-N

物化性质

• 沸点：
  455.0±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-[(dimethylamino)methylidene]-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate 在 乙醇 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 1-methyl-8-(phenylamino)-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
• 作为产物：
  描述：

  4,5,6,7-四氢-1-甲基-7-氧代-1H-吲唑-3-羧酸乙酯 、 N,N-二甲基甲酰胺二异丙基缩醛 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 6-[(dimethylamino)methylidene]-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate
  参考文献：
  名称：

  Identification of 4,5-Dihydro-1H-pyrazolo[4,3-h]quinazoline Derivatives as a New Class of Orally and Selective Polo-Like Kinase 1 Inhibitors

  摘要：

  Polo-like kinase 1 (Plk1) is a fundamental regulator of mitotic progression whose overexpression is often associated with oncogenesis and therefore is recognized as an attractive therapeutic target in the treatment of proliferative diseases. Here we discuss the structure-activity relationship of the 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline class of compounds that emerged from a high throughput screening (HTS) campaign as potent inhibitors of Plk1 kinase. Furthermore, we describe the discovery of 49, 8-{[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]amino}-1-methyl-4,5-dihydro-1H-pyrazolo-[4,3-h]quinazoline-3-carboxamide, as a highly potent and specific ATP mimetic inhibitor of Plk1 (IC(50) = 0.007 mu M) as well as its crystal structure in complex with the methylated Plk1(36-345) construct. Compound 49 was active in cell proliferation against different tumor cell lines with 1050 values in the submicromolar range and active in vivo in the HCT116 xenograft model where it showed 82% tumor growth inhibition after repeated oral administration.

  DOI：

  10.1021/jm901713n

文献信息

• 吡唑并[4,3-h]喹唑啉类化合物及其用途
  申请人：江苏艾凡生物医药有限公司

  公开号：CN107383019B

  公开（公告）日：2019-10-15

  本发明涉及一类如下通式I所示的吡唑并[4,3‑h]喹唑啉类衍生物及其用途，该类化合物具有抑制细胞周期蛋白依赖性酶家族(CDKs)中不同亚型例如CDK4/6的活性，为预防和治疗癌症、代谢与免疫疾病、心血管病以及神经性疾病提供新的手段。
• [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-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。
• SUBSTITUTED PYRAZOLO-QUINAZOLINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  申请人：Caruso Michele

  公开号：US20100216808A1

  公开（公告）日：2010-08-26

  Pyrazolo-quinazoline derivatives of formula (I) 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（I）中所定义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；本发明中的化合物在治疗与蛋白激酶活性失调相关的疾病，如癌症中可能有用。