1-tert-butyl-4-(piperidin-4-yl-methyl)piperazine | 1013330-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-tert-butyl-4-(piperidin-4-yl-methyl)piperazine
• 英文别名: 1-tert-butyl-4-(piperidin-4-ylmethyl)piperazine
• CAS: 1013330-25-0
• 化学式: C₁₄H₂₉N₃
• mdl: MFCD13489502
• 分子量: 239.404
• InChiKey: BHWJKRURWWSGAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  18.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-tert-butyl-4-(piperidin-4-yl-methyl)piperazine 、 3,3-二苯基丙酸 在 4-二甲氨基吡啶 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 1-(4-((4-tert-butylpiperazin-1-yl)methyl)piperidin-1-yl)-3,3-diphenylpropan-1-one
  参考文献：
  名称：

  WO2008/31227

  摘要：

  公开号：
• 作为产物：
  描述：

  1-(1-benzylpiperidin-4-yl)methyl-4-tert-butyl-piperazine 在 钯 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 1-tert-butyl-4-(piperidin-4-yl-methyl)piperazine
  参考文献：
  名称：

  DIARYL PIPERIDINE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS

  摘要：

  本发明揭示了对于其特征为不需要的钙通道活性，特别是不需要的N型钙通道活性的状况，有效改善的方法和化合物。具体而言，本发明揭示了一系列二芳基哌啶化合物，其通式为（I），其中X为连接剂，Y可以是C、O、S或N。

  公开号：

  US20100168103A1

文献信息

• Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and <i>In Vivo</i> Efficacy in the <i>Plasmodium falciparum</i> NSG Mouse Model
  作者：André Horatscheck、Ana Andrijevic、Aloysius T. Nchinda、Claire Le Manach、Tanya Paquet、Lutete Peguy Khonde、Jean Dam、Kailash Pawar、Dale Taylor、Nina Lawrence、Christel Brunschwig、Liezl Gibhard、Mathew Njoroge、Janette Reader、Mariëtte van der Watt、Kathryn Wicht、Ana Carolina C. de Sousa、John Okombo、Keletso Maepa、Timothy J. Egan、Lyn-Marie Birkholtz、Gregory S. Basarab、Sergio Wittlin、Paul V. Fish、Leslie J. Street、James Duffy、Kelly Chibale

  DOI：10.1021/acs.jmedchem.0c01411

  日期：2020.11.12

  cardiotoxicity and were addressed through structure–activity and structure–property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated

  一系列 2,4-二取代咪唑并吡啶源自 SoftFocus 激酶文库，是从针对人类疟疾寄生虫恶性疟原虫的高通量表型筛选中鉴定出来的。命中化合物显示出中等的无性血阶段活性。在先导优化过程中，标记了几个问题，例如对多重耐药 K1 菌株的交叉耐药性、体外细胞毒性和心脏毒性，并通过结构-活性和结构-性质关系研究得到解决。在小鼠中评估了化合物的药代动力学特性，这些化合物显示出理想的体外活性、细胞毒性的选择性窗口和微粒体代谢稳定性。领跑者化合物37在小鼠中显示出良好的暴露，并结合良好的体外抗疟原虫活性，这在恶性疟原虫NOD -scid IL-2Rγ无效（NSG）小鼠模型中转化为体内功效。初步机理研究表明抑制血红素形成是一种促成作用方式。
• [EN] RAPIDLY ACCELERATING FIBROSARCOMA PROTEIN DEGRADING COMPOUNDS AND ASSOCIATED METHODS OF USE<br/>[FR] COMPOSÉS DE DÉGRADATION DE PROTÉINE DE FIBROSARCOME RAPIDEMENT ACCÉLÉRÉ ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2022047145A1

  公开（公告）日：2022-03-03

  Bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (Raf, such as c-Raf, A-Raf, and/or B-Raf), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds Raf, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本文描述了作为快速加速纤维肉瘤（Raf，如c-Raf、A-Raf和/或B-Raf）调节剂的双功能化合物。具体来说，本公开的异双功能化合物在一端含有结合到cereblon E3泛素连接酶的部分，另一端含有结合Raf的部分，使目标蛋白质靠近泛素连接酶以实现目标蛋白质的降解（和抑制）。本公开的异双功能化合物表现出与目标蛋白质的降解/抑制相关的广泛的药理活性。由于目标蛋白质异常调节导致的疾病或疾病可以通过本公开的化合物和组合物进行治疗或预防。
• Modulators of proteolysis and associated methods of use
  申请人：Arvinas Operations, Inc.

  公开号：US11161841B2

  公开（公告）日：2021-11-02

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 Kirsten 大鼠肉瘤蛋白（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与相应 E3 泛素连接酶结合的 Von Hippel-Lindau、cereblon、Apotosis Proteins 抑制剂或小鼠双敏同源物 2 配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白的聚集、积累和/或过度激活而导致的疾病或失调。
• MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20190315732A1

  公开（公告）日：2019-10-17

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
• [EN] DIARYL PIPERIDINE COMPOUNDS AS CALCIUM CHANNEL BLOCKERS<br/>[FR] COMPOSÉS DE DIARYLE PIPERIDINE UTILISÉS EN TANT QUE BLOQUEURS DE CANAUX CALCIQUES
  申请人：NEUROMED PHARMACEUTICALS LTD

  公开号：WO2008031227A1

  公开（公告）日：2008-03-20

  [EN] Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted N-type calcium channel activity are disclosed. Specifically, a series of diaryl piperidine compounds are disclosed of the general formula (I) where X is a linker and Y may be C, O, S or N.
  [FR] La présente invention concerne des procédés et des composés efficaces dans l'amélioration de pathologies caractérisées par une activité indésirable du canal calcique, en particulier par une activité indésirable du canal calcique de type N. L'invention concerne en particulier une série de composés de diaryle pipéridine de formule générale (I) dans laquelle X représente un lieur et dans laquelle Y peut désigner C, O, S ou N.