ethyl (Z)-3-[5-(4-chlorophenyl)-1H-tetrazol-1-yl]propenoate | 1077627-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl (Z)-3-[5-(4-chlorophenyl)-1H-tetrazol-1-yl]propenoate
• 英文别名: ethyl (Z)-3-[5-(4-chlorophenyl)tetrazol-1-yl]prop-2-enoate
• CAS: 1077627-06-5
• 化学式: C₁₂H₁₁ClN₄O₂
• 分子量: 278.698
• InChiKey: OBXNRTWLQUOURS-FPLPWBNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-(4-氯苯基)-1H-四唑 、 丙炔酸乙酯 在 三乙胺 作用下， 以 乙腈 为溶剂， 以33%的产率得到ethyl (Z)-3-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]propenoate
  参考文献：
  名称：

  Inhibition of the CRM1-mediated nucleocytoplasmic transport by N-azolylacrylates: Structure–activity relationship and mechanism of action

  摘要：

  CRM1-mediated nucleocytoplasmic transport plays an important role in many cellular processes and diseases. To investigate the structural basis required for the inhibition of the CRM1-mediated nuclear export we have synthesized analogs of a previously identified small molecule lead compound and monitored their activity against the Rev function of the human immunodeficiency virus. Microscopy studies show that the active congeners of this series inhibit the nucleocytoplasmic transport of Rev and the co-localization between Rev and CRM1 in living cells. Mechanism of action studies show their interaction with the Cys528 residue of CRM1 involving a Michael-addition type of reaction. However, structure-activity relationship demonstrates strict constraints to the structure of the inhibitors, and shows that activity is not solely correlated to Michael-addition suggesting a more complex mechanism of action. Our results are suggestive for the existence of a well-defined interaction at the CRM1-NES binding site. In addition, the most selective congener inhibited the HIV-1 production in latently infected cells. These specific CRM1 inhibitors are of interest as tool for analyzing the mechanisms of post-transcriptional control of gene expression and provide insight in the design of new agents. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.051

文献信息

• Inhibition of the CRM1-mediated nucleocytoplasmic transport by N-azolylacrylates: Structure–activity relationship and mechanism of action
  作者：Tine Van Neck、Christophe Pannecouque、Els Vanstreels、Miguel Stevens、Wim Dehaen、Dirk Daelemans

  DOI：10.1016/j.bmc.2008.09.051

  日期：2008.11

  CRM1-mediated nucleocytoplasmic transport plays an important role in many cellular processes and diseases. To investigate the structural basis required for the inhibition of the CRM1-mediated nuclear export we have synthesized analogs of a previously identified small molecule lead compound and monitored their activity against the Rev function of the human immunodeficiency virus. Microscopy studies show that the active congeners of this series inhibit the nucleocytoplasmic transport of Rev and the co-localization between Rev and CRM1 in living cells. Mechanism of action studies show their interaction with the Cys528 residue of CRM1 involving a Michael-addition type of reaction. However, structure-activity relationship demonstrates strict constraints to the structure of the inhibitors, and shows that activity is not solely correlated to Michael-addition suggesting a more complex mechanism of action. Our results are suggestive for the existence of a well-defined interaction at the CRM1-NES binding site. In addition, the most selective congener inhibited the HIV-1 production in latently infected cells. These specific CRM1 inhibitors are of interest as tool for analyzing the mechanisms of post-transcriptional control of gene expression and provide insight in the design of new agents. (C) 2008 Elsevier Ltd. All rights reserved.