2-[4-(4-nitro-2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanol | 859027-18-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[4-(4-nitro-2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanol
• 英文别名: 2-{4-[4-nitro-2-(trifluoromethyl)benzyl]piperazin-1-yl}ethan-1-ol；2-[4-(4-Nitro-2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanol；2-[4-[[4-nitro-2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]ethanol
• CAS: 859027-18-2
• 化学式: C₁₄H₁₈F₃N₃O₃
• 分子量: 333.31
• InChiKey: WZHIUQAETBFSLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[4-(4-nitro-2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanol 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 30.0h， 生成 3-[(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-N-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}-3-(trifluoromethyl)phenyl)-4-methylbenzamide
  参考文献：
  名称：

  [EN] COMPOSITIONS FOR INDUCING TUMOR IMMUNITY AND REDUCING DRUG TOLERANCE
  [FR] COMPOSITIONS POUR INDUIRE UNE IMMUNITÉ TUMORALE ET RÉDUIRE LA TOLÉRANCE AUX MÉDICAMENTS

  摘要：

  本文描述了与脂质结合的HSP-90抑制剂，包括该结合物的组合物，以及使用该组合物治疗癌症的方法。

  公开号：

  WO2022082108A1
• 作为产物：
  描述：

  N-羟乙基哌嗪 、 1-(溴甲基)-4-硝基-2-(三氟甲基)苯 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以90%的产率得到2-[4-(4-nitro-2-trifluoromethyl-benzyl)-piperazin-1-yl]-ethanol
  参考文献：
  名称：

  [EN] COMPOSITIONS FOR INDUCING TUMOR IMMUNITY AND REDUCING DRUG TOLERANCE
  [FR] COMPOSITIONS POUR INDUIRE UNE IMMUNITÉ TUMORALE ET RÉDUIRE LA TOLÉRANCE AUX MÉDICAMENTS

  摘要：

  本文描述了与脂质结合的HSP-90抑制剂，包括该结合物的组合物，以及使用该组合物治疗癌症的方法。

  公开号：

  WO2022082108A1

文献信息

• [EN] SUBSTITUTED PYRIMIDINYL AND PYRIDINYL-PYRROLOPYRIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS<br/>[FR] PYRIMIDINYL ET PYRIDINYL-PYRROLOPYRIDINONES SUBSTITUÉS, PROCÉDÉ POUR LEUR PRÉPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASES
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2014072220A1

  公开（公告）日：2014-05-15

  The present invention relates to substituted pyrimidinyl- and pyridinylpyrrolopyridinone compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular RET family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions containing these compounds.

  本发明涉及替代嘧啶基和吡啶基吡咯吡啶酮化合物，这些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 RET 家族激酶方面具有用途。本发明还提供了制备这些化合物的方法，包括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。
• SUBSTITUTED PYRIMIDINYL AND PYRIDINYL-PYRROLOPYRIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  申请人：NERVIANO MEDICAL SCIENCES S.r.l.

  公开号：US20150299192A1

  公开（公告）日：2015-10-22

  The present invention relates to substituted pyrimidinyl- and pyridinylpyrrolopyridinone compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular RET family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions containing these compounds.

  本发明涉及取代的嘧啶基和吡啶基吡咯吡啶酮化合物，其调节蛋白激酶活性，因此在治疗由失调的蛋白激酶活性引起的疾病中特别有用，特别是RET家族激酶。本发明还提供了制备这些化合物的方法、包含这些化合物的制药组合物以及利用含有这些化合物的制药组合物治疗疾病的方法。
• Discovery of 3-[2-(Imidazo[1,2-<i>b</i>]pyridazin-3-yl)ethynyl]-4-methyl-<i>N</i>-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant
  作者：Wei-Sheng Huang、Chester A. Metcalf、Raji Sundaramoorthi、Yihan Wang、Dong Zou、R. Mathew Thomas、Xiaotian Zhu、Lisi Cai、David Wen、Shuangying Liu、Jan Romero、Jiwei Qi、Ingrid Chen、Geetha Banda、Scott P. Lentini、Sasmita Das、Qihong Xu、Jeff Keats、Frank Wang、Scott Wardwell、Yaoyu Ning、Joseph T. Snodgrass、Marc I. Broudy、Karin Russian、Tianjun Zhou、Lois Commodore、Narayana I. Narasimhan、Qurish K. Mohemmad、John Iuliucci、Victor M. Rivera、David C. Dalgarno、Tomi K. Sawyer、Tim Clackson、William C. Shakespeare

  DOI：10.1021/jm100395q

  日期：2010.6.24

  In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of I1e315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC(50)s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CM L, including patients refractory to all currently approved therapies.
• US9604980B2
  申请人：——

  公开号：US9604980B2

  公开（公告）日：2017-03-28
• Rapid Discovery of a Novel Series of Abl Kinase Inhibitors by Application of an Integrated Microfluidic Synthesis and Screening Platform
  作者：Bimbisar Desai、Karen Dixon、Elizabeth Farrant、Qixing Feng、Karl R. Gibson、Willem P. van Hoorn、James Mills、Trevor Morgan、David M. Parry、Manoj K. Ramjee、Christopher N. Selway、Gary J. Tarver、Gavin Whitlock、Adrian G. Wright

  DOI：10.1021/jm400099d

  日期：2013.4.11

  Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC(50) > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.