1-乙基氧基羰基-3-[4-(4-甲基-1-哌嗪)-苯甲酰基氨基]-5-boc-4,6-二氢-吡咯并[3,4-c]吡唑 | 761443-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-乙基氧基羰基-3-[4-(4-甲基-1-哌嗪)-苯甲酰基氨基]-5-boc-4,6-二氢-吡咯并[3,4-c]吡唑
• 中文别名: 5-(叔丁氧羰基)-3-[[4-(4-甲基哌嗪-1-基)苯甲酰基]氨基]-4,6-二氢吡咯并[3,4-C]吡唑-1-羧酸乙酯
• 英文名称: 5-tert-butyl 1-ethyl 3-{[4-(4-methylpiperazin-1-yl)benzoyl]amino}-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylate
• 英文别名: 3-[4-(N-methylpiperazin-1-yl)benzamido]-1-ethoxycarbonyl-5-t-butyloxycarbonyl-4,6-dihydropyrrolo[3,4-c]pyrazole；1-Ethyloxycarbonyl-3-[4-(4-methyl-piperazin-1-YL)-benzoylamino]-5-boc-4,6-dihydro-pyrrolo[3,4-C]pyrazole；5-O-tert-butyl 1-O-ethyl 3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-4,6-dihydropyrrolo[3,4-c]pyrazole-1,5-dicarboxylate
• CAS: 761443-69-0
• 化学式: C₂₅H₃₄N₆O₅
• 分子量: 498.582
• InChiKey: YLYRHIITRIEACU-UHFFFAOYSA-N

物化性质

• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-乙基氧基羰基-3-[4-(4-甲基-1-哌嗪)-苯甲酰基氨基]-5-boc-4,6-二氢-吡咯并[3,4-c]吡唑 在 盐酸 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 5-((2R)-2-甲氧基-2-苯基乙酰基)-3-[[4-(4-甲基哌嗪-1-基)苯甲酰基]氨基]-5,6-二氢吡咯并[3,4-c]吡唑-1(4H)-羧酸乙酯
  参考文献：
  名称：

  （R）-N-[5-(2-甲氧基-2-苯基乙酰基)-1,4, 5,6-四氢吡咯并[3,4-c]吡唑-3-基]-4-(4-甲 基哌嗪-1-基)苯甲酰胺的合成方法

  摘要：

  本发明属于医药技术领域，涉及PHA739358（Danusertib）即（R）‑N‑[5‑(2‑甲氧基‑2‑苯基乙酰基)‑1,4,5,6‑四氢吡咯并[3,4‑c]吡唑‑3‑基]‑4‑(4‑甲基哌嗪‑1‑基)苯甲酰胺的制备，共设计了四条反应路线，以简单易得的甘氨酸为原料，经加成、酯化、氨基保护、环合等反应制得（R）‑N‑[5‑(2‑甲氧基‑2‑苯基乙酰基)‑1,4,5,6‑四氢吡咯并[3,4‑c]吡唑‑3‑基]‑4‑(4‑甲基哌嗪‑1‑基)苯甲酰胺，路线1、2、4收率可达25%以上，路线3收率可达20%以上。本发明具有反应步骤短、后处理操作简便、耗时短、收率高、总成本低的优点。为抗肿瘤药物PHA739358的制备提供了新方法。

  公开号：

  CN104072498B
• 作为产物：
  描述：

  3-氨基-5-叔丁氧羰基-吡咯并[3,4-C]吡唑 在 草酰氯 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 1-乙基氧基羰基-3-[4-(4-甲基-1-哌嗪)-苯甲酰基氨基]-5-boc-4,6-二氢-吡咯并[3,4-c]吡唑
  参考文献：
  名称：

  （R）-N-[5-(2-甲氧基-2-苯基乙酰基)-1,4, 5,6-四氢吡咯并[3,4-c]吡唑-3-基]-4-(4-甲 基哌嗪-1-基)苯甲酰胺的合成方法

  摘要：

  本发明属于医药技术领域，涉及PHA739358（Danusertib）即（R）‑N‑[5‑(2‑甲氧基‑2‑苯基乙酰基)‑1,4,5,6‑四氢吡咯并[3,4‑c]吡唑‑3‑基]‑4‑(4‑甲基哌嗪‑1‑基)苯甲酰胺的制备，共设计了四条反应路线，以简单易得的甘氨酸为原料，经加成、酯化、氨基保护、环合等反应制得（R）‑N‑[5‑(2‑甲氧基‑2‑苯基乙酰基)‑1,4,5,6‑四氢吡咯并[3,4‑c]吡唑‑3‑基]‑4‑(4‑甲基哌嗪‑1‑基)苯甲酰胺，路线1、2、4收率可达25%以上，路线3收率可达20%以上。本发明具有反应步骤短、后处理操作简便、耗时短、收率高、总成本低的优点。为抗肿瘤药物PHA739358的制备提供了新方法。

  公开号：

  CN104072498B

文献信息

• Pyrrolo[3,4-c]pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
  申请人：Pfizer Italia S.r.l.

  公开号：US07141568B2

  公开（公告）日：2006-11-28

  Pyrrolo[3,4-c]pyrazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, 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（I）的吡咯并[3,4-c]吡唑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；本发明中的化合物在治疗中可能有用，用于治疗与蛋白激酶活性失调相关的疾病，如癌症。
• Bicyclo-pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
  申请人：Abrate Francesca

  公开号：US20070037790A1

  公开（公告）日：2007-02-15

  Compounds which are pyrrolo-pyrazole derivatives and pharmaceutically acceptable salts thereof, together with the process for their preparation and pharmaceutical compositions thereof are disclosed; these compounds or compositions are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, cell proliferative disorders, Alzheimer's disease, viral infections, auto-immune diseases and neurodegenerative disorders.

  本发明公开了吡咯-吡唑衍生物及其药学上可接受的盐，以及其制备方法和制药组合物；这些化合物或组合物在治疗由于和/或与蛋白激酶活性改变有关的疾病方面是有用的，例如癌症、细胞增殖性疾病、阿尔茨海默病、病毒感染、自身免疫性疾病和神经退行性疾病。
• Potent and Selective Aurora Inhibitors Identified by the Expansion of a Novel Scaffold for Protein Kinase Inhibition
  作者：Daniele Fancelli、Daniela Berta、Simona Bindi、Alexander Cameron、Paolo Cappella、Patrizia Carpinelli、Cornel Catana、Barbara Forte、Patrizia Giordano、Maria Laura Giorgini、Sergio Mantegani、Aurelio Marsiglio、Maurizio Meroni、Juergen Moll、Valeria Pittalà、Fulvia Roletto、Dino Severino、Chiara Soncini、Paola Storici、Roberto Tonani、Mario Varasi、Anna Vulpetti、Paola Vianello

  DOI：10.1021/jm049076m

  日期：2005.4.1

  Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC(50) of 0.027 microM in the enzymatic assay for Aur-A inhibition and IC(50)s between 0.05 microM and 0.5 microM for the inhibition of proliferation of different tumor cell lines.
• 1,4,5,6-Tetrahydropyrrolo[3,4-<i>c</i>]pyrazoles:  Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile
  作者：Daniele Fancelli、Jürgen Moll、Mario Varasi、Rodrigo Bravo、Roberta Artico、Daniela Berta、Simona Bindi、Alexander Cameron、Ilaria Candiani、Paolo Cappella、Patrizia Carpinelli、Walter Croci、Barbara Forte、Maria Laura Giorgini、Jan Klapwijk、Aurelio Marsiglio、Enrico Pesenti、Maurizio Rocchetti、Fulvia Roletto、Dino Severino、Chiara Soncini、Paola Storici、Roberto Tonani、Paola Zugnoni、Paola Vianello

  DOI：10.1021/jm060897w

  日期：2006.11.30

  The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.
• WO2005/5427
  申请人：——

  公开号：——

  公开（公告）日：——