3-(2-benzyl-5-methylazido-3-isobutyl-isoxazolidine-3-yl)-ethanol

• 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: 3-(2-benzyl-5-methylazido-3-isobutyl-isoxazolidine-3-yl)-ethanol
• 英文别名: 2-[(3S,5R)-5-(azidomethyl)-2-benzyl-3-(2-methylpropyl)-1,2-oxazolidin-3-yl]ethanol
• 化学式: C₁₇H₂₆N₄O₂
• 分子量: 318.419
• InChiKey: IOUZAKOZNDIRHM-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-benzyl-5-methylazido-3-isobutyl-isoxazolidine-3-yl)-ethanol 在 水 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 2-[(3S,5R)-5-(aminomethyl)-2-benzyl-3-(2-methylpropyl)-1,2-oxazolidin-3-yl]ethanol
  参考文献：
  名称：

  Transcriptional Up-regulation in Cells Mediated by a Small Molecule

  摘要：

  Activator artificial transcription factors, molecules that seek out specific genes and up-regulate their transcription, are desirable as mechanistic tools and as potential therapeutic agents. One challenge has been the identification of small molecule-based activator ATFs that function in cellular systems. Here we demonstrate that an amphipathic isoxazolidine activates transcription up to 80-fold in human cells when targeted to a specific promoter. Analogous to natural transcriptional activators, the function of the isoxazolidine appears to be independent of the DNA-targeting moiety, suggesting that the molecule will be effective in a variety of contexts. This is thus a critical step toward activator ATFs constructed from small molecule components.

  DOI：

  10.1021/ja0736865
• 作为产物：
  描述：

  3-(2-benzyl-5-methylazido-3-isobutyl-isoxazolidine-3-yl)-ethanal 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 以106 mg的产率得到3-(2-benzyl-5-methylazido-3-isobutyl-isoxazolidine-3-yl)-ethanol
  参考文献：
  名称：

  Transcriptional Up-regulation in Cells Mediated by a Small Molecule

  摘要：

  Activator artificial transcription factors, molecules that seek out specific genes and up-regulate their transcription, are desirable as mechanistic tools and as potential therapeutic agents. One challenge has been the identification of small molecule-based activator ATFs that function in cellular systems. Here we demonstrate that an amphipathic isoxazolidine activates transcription up to 80-fold in human cells when targeted to a specific promoter. Analogous to natural transcriptional activators, the function of the isoxazolidine appears to be independent of the DNA-targeting moiety, suggesting that the molecule will be effective in a variety of contexts. This is thus a critical step toward activator ATFs constructed from small molecule components.

  DOI：

  10.1021/ja0736865

文献信息

• CBP AND p300-MEDIATED TRANSCRIPTION MODULATORS AND RELATED METHODS
  申请人：Mapp Anna

  公开号：US20150025045A1

  公开（公告）日：2015-01-22

  The present invention relates to gene regulation. In particular, the present invention provides small compounds capable of modulating p300 and/or CBP-mediated transcription and related methods of therapeutic and research use. In addition, the present invention provides methods for treating conditions associated with aberrant p300 and/or CBP-mediated transcription with p300 and/or CBP-mediated transcription modulators (e.g., p300 and/or CBP-mediated transcription inhibitors).

  本发明涉及基因调控。具体而言，本发明提供了能够调节p300和/或CBP介导的转录作用的小分子化合物及其治疗和研究使用的相关方法。此外，本发明还提供了使用p300和/或CBP介导的转录调节剂（例如，p300和/或CBP介导的转录抑制剂）治疗与异常p300和/或CBP介导的转录相关的疾病的方法。
• Inhibition of ErbB2(Her2) expression with small molecule transcription factor mimics
  作者：Lori W. Lee、Christopher E.C. Taylor、Jean-Paul Desaulniers、Manchao Zhang、Jonas W. Højfeldt、Quintin Pan、Anna K. Mapp

  DOI：10.1016/j.bmcl.2009.08.090

  日期：2009.11

  Small molecules that mimic the transcriptional activation domain of eukaryotic transcriptional activators have the potential to serve as effective inhibitors of transcriptional processes. Here we show that one class of transcriptional activation domain mimics, amphipathic isoxazolidines, can be converted into inhibitors of gene expression mediated by the transcriptional activator ESX through small structural modi. cations. Addition of the small molecules leads to decreased expression of the cell surface growth receptor ErbB2(Her2) in ErbB2-positive cancer cells and, correspondingly, decreased proliferation. (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] ESX-MEDIATED TRANSCRIPTION MODULATORS AND RELATED METHODS<br/>[FR] MODULATEURS DE TRANSCRIPTION À MÉDIATION ASSURÉE PAR LE GÈNE ESX ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV MICHGIAN

  公开号：WO2013040436A2

  公开（公告）日：2013-03-21

  The present invention relates to gene regulation. In particular, the present invention provides small compounds capable of modulating ESX-mediated transcription and related methods of therapeutic and research use. In addition, the present invention provides methods for treating conditions associated with aberrant EGFR expression with ESX-mediated transcription modulators (e.g., ESX-mediated transcription inhibitors).
• [EN] CBP and p300-MEDIATED TRANSCRIPTION MODULATORS AND RELATED METHODS<br/>[FR] MODULATEURS DE TRANSCRIPTION À MÉDIATION ASSURÉE PAR LES PROTÉINES P300/CBP ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV MICHIGAN

  公开号：WO2013040439A2

  公开（公告）日：2013-03-21

  The present invention relates to gene regulation. In particular, the present invention provides small compounds capable of modulating p300 and/or CBP-mediated transcription and related methods of therapeutic and research use. In addition, the present invention provides methods for treating conditions associated with aberrant p300 and/or CBP -mediated transcription with p300 and/or CBP-mediated transcription modulators (e.g., p300 and/or CBP-mediated transcription inhibitors).