tert-butyl 4-(4-nitro-2-(trifluoromethyl)benzyl)piperazine-1-carboxylate | 859027-32-0

• 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: tert-butyl 4-(4-nitro-2-(trifluoromethyl)benzyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-[[4-nitro-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate；tert-butyl 4-[[4-nitro-2-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate
• CAS: 859027-32-0
• 化学式: C₁₇H₂₂F₃N₃O₄
• 分子量: 389.375
• InChiKey: CMIHEMQOKUUROU-UHFFFAOYSA-N

物化性质

• 沸点：
  425.1±45.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-nitro-2-(trifluoromethyl)benzyl)piperazine-1-carboxylate 在 铁粉 、 氯化铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 4-(4-(3-iodo-4-methylbenzoylamino)-2-(trifluoromethyl)benzyl)piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  BCR-ABL DIPLOID INHIBITOR, PREPARATION METHOD THEREFOR, AND USES THEREOF

  摘要：

  公开号：

  EP3133069B1
• 作为产物：
  描述：

  2-甲基-5-硝基三氟甲苯 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 过氧化苯甲酰 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 tert-butyl 4-(4-nitro-2-(trifluoromethyl)benzyl)piperazine-1-carboxylate
  参考文献：
  名称：

  E3泛素连接酶配体化合物、基于该配体化合物开发的蛋白降解剂及它们的应用

  摘要：

  本公开涉及式(I)和式(II)的化合物或其盐、对映异构体、立体异构体、溶剂化物、同位素富集类似物、前药或多晶型物及其应用。本公开还涉及包含作为活性成分的式(I)和式(II)的化合物或其盐、对映异构体、立体异构体、溶剂化物、同位素富集类似物、前药或多晶型物的药物组合物及其应用。

  公开号：

  CN116239566A

文献信息

• [EN] DEGRADATION OF PROTEIN KINASES BY CONJUGATION OF PROTEIN KINASE INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE<br/>[FR] DÉGRADATION DE PROTÉINES KINASES PAR CONJUGAISON D'INHIBITEURS DE PROTÉINE KINASE AVEC UN LIGAND DE LA LIGASE E3 ET PROCÉDÉS D'UTILISATION
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2018089736A1

  公开（公告）日：2018-05-17

  The present application provides bifunctional compounds of Formula (I), or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases (e.g., Bcr-Abl). The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.

  本申请提供了Formula (I)的双功能化合物，或其对映体、非对映体或立体异构体，或其药学上可接受的盐、水合物、溶剂合物或前药，这些化合物作为蛋白激酶（例如Bcr-Abl）的蛋白降解诱导基团。本申请还涉及通过使用将泛素连接酶结合基团与能够结合到一个或多个蛋白激酶的配体相连的双功能化合物的方法，用于靶向降解一个或多个蛋白激酶，可用于治疗受蛋白激酶调节的疾病。
• [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.
• EP3778590
  申请人：——

  公开号：——

  公开（公告）日：——