1,4,4-三甲基-7-氧代-4,5,6,7-四氢-1H-吲唑-3-羧酸乙酯 | 802541-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1,4,4-三甲基-7-氧代-4,5,6,7-四氢-1H-吲唑-3-羧酸乙酯
• 英文名称: ethyl 1,4,4-trimethyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate
• 英文别名: ethyl 1,4,4-trimethyl-7-oxo-5,6-dihydroindazole-3-carboxylate
• CAS: 802541-48-6
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: MPKAOSDCKDNDBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1,4,4-三甲基-7-氧代-4,5,6,7-四氢-1H-吲唑-3-羧酸乙酯 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 39.0h， 生成 ethyl 8-{[3-chloro-4-(4-methylpiperazin-1-yl)phenyl]amino}-1,4,4-trimethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate
  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 (3-methoxy-6,6-dimethyl-2-oxocyclohex-3-en-1-yl)(oxo)acetate 、 甲基肼 在 乙酸乙酯 、 Brine 、 Sodium sulfate-III 、 crude material 、 silica gel 、 ethyl acetate dichloromethane 作用下， 以 溶剂黄146 、 水 为溶剂， 反应 16.0h， 以to obtain the pure title compound (4.8 g, 47.7% yield)的产率得到1,4,4-三甲基-7-氧代-4,5,6,7-四氢-1H-吲唑-3-羧酸乙酯
  参考文献：
  名称：

  Pyrazolo quinazoline derivatives, process for their preparation and their use as kinase inhibitors

  摘要：

  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，如癌症方面有用。

  公开号：

  US08541429B2

文献信息

• 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。
• Synthesis and SAR of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent and selective CDK4/6 inhibitors
  作者：Hui Zhao、Xiaoxia Hu、Kai Cao、Yue Zhang、Kuantao Zhao、Chunlei Tang、Bainian Feng

  DOI：10.1016/j.ejmech.2018.08.043

  日期：2018.9

  CDK4/6 pathway is an attractive target for development of anti-cancer drugs. Herein, we reported the design and synthesis of a series of 4,5-dihydro-1H-pyrazolo [4,3-h]guinazoline derivatives as selective CDK4/6 inhibitors. Applied with the optimizing strategy to the initial scaffold, it is found that compound 13n is able to selectively inhibit CDK4 and CDK6 with IC50 values 0.01 and 0.026 mu M, respectively. The compound showed good anti-proliferative activity when tested in a panel of tumor cell lines with CDK4/6 related mechanism of action, the results clearly suggest that compound 13n works much better than Ly2385219 which is a selective CDK4/6 inhibitor. This compound was also found to have favorable pharmacokinetic parameters. Taken together, compound 13n could be selected for further preclinical evaluation. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Identification of <i>N</i>,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1<i>H</i>-pyrazolo[4,3-<i>h</i>]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor
  作者：Maria Gabriella Brasca、Nadia Amboldi、Dario Ballinari、Alexander Cameron、Elena Casale、Giovanni Cervi、Maristella Colombo、Francesco Colotta、Valter Croci、Roberto D’Alessio、Francesco Fiorentini、Antonella Isacchi、Ciro Mercurio、Walter Moretti、Achille Panzeri、Wilma Pastori、Paolo Pevarello、Francesca Quartieri、Fulvia Roletto、Gabriella Traquandi、Paola Vianello、Anna Vulpetti、Marina Ciomei

  DOI：10.1021/jm9006559

  日期：2009.8.27

  The discovery of a novel class of inhibitors of cyclin dependent kinases (CDKs) is described, Starting from compound 1, showing good potency as inhibitor of CDKs but being poorly selective against a panel of serine-threonine and tyrosine kinases, new analogues were synthesize cl, Enhancement in selectivity, antiproliferative activity against A2780 human ovarian carcinoma cells, and optimization of the physical properties and pharmacokinetic profile led to the identification of highly potent and orally available compounds. Compound 28 (PHA-848125), which in the preclinical xenograft A2780 human ovarian carcinoma model showed good efficacy and was well tolerated upon repeated daily treatments, was identified its a drug candidate for further development. Compound 28 is Currently undergoing phase I and phase II clinical trials.