ethyl (2Z)-3-(2-phenyl-1H-imidazol-1-yl)-propenoate | 1077626-76-6

• 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 (2Z)-3-(2-phenyl-1H-imidazol-1-yl)-propenoate
• 英文别名: ethyl (Z)-3-(2-phenylimidazol-1-yl)prop-2-enoate
• CAS: 1077626-76-6
• 化学式: C₁₄H₁₄N₂O₂
• 分子量: 242.277
• InChiKey: YFKXFOCASJBSEU-NTMALXAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-苯基咪唑 、 丙炔酸乙酯 以 甲苯 为溶剂， 以31%的产率得到(E)-ethyl 3-(2-phenyl-1H-imidazol-1-yl)acrylate
  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

• NUCLEAR TRANSPORT MODULATORS AND USES THEREOF
  申请人：Shacham Sharon

  公开号：US20110275607A1

  公开（公告）日：2011-11-10

  The invention generally relates to the field of nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to new substituted-heterocyclic azole compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity such as in treating cancer and other neoplastic disorders, inflammatory diseases, disorders of abnormal tissue growth and fibrosis including cardiomyopathy, pulmonary fibrosis, hepatic fibrosis, glomerulonephritis, and other renal disorders, and for the treatment of viral infections (both acute and chronic).

  本发明通常涉及核运输调节剂领域，例如CRM1抑制剂，更具体地涉及新的取代杂环唑类化合物，这些化合物的合成和使用以及它们的制药组合物，例如在治疗、调节和/或预防与CRM1活性相关的生理状况方面的用途，例如治疗癌症和其他肿瘤性疾病、炎症性疾病、异常组织生长和纤维化疾病，包括心肌病、肺纤维化、肝纤维化、肾小球肾炎和其他肾脏疾病，以及治疗病毒感染（急性和慢性）。
• US8513230B2
  申请人：——

  公开号：US8513230B2

  公开（公告）日：2013-08-20
• US9550757B2
  申请人：——

  公开号：US9550757B2

  公开（公告）日：2017-01-24
• 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.