EMK 181 | 133550-05-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: EMK 181
• 英文别名: 2-[(3-Fluoro-4-methoxyphenyl)methylidene]propanedinitrile
• CAS: 133550-05-7
• 化学式: C₁₁H₇FN₂O
• 分子量: 202.188
• InChiKey: KCRDGGROWVQVJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  EMK 181 在 三溴化硼 作用下， 生成 EMK 211
  参考文献：
  名称：

  Benzylidenemalononitrile compounds as activators of cell resistance to oxidative stress and modulators of multiple signaling pathways. A structure–activity relationship study

  摘要：

  Benzylidenemalononitrile (BMN) tyrphostins are well known as potent tyrosine kinase inhibitors. Moreover, in recent years it has been recognized that members of the tyrphostin family possess additional biological activities independent of their ability to inhibit protein tyrosine kinases. In this study, we examined the relationship between the structure of 49 BMNs and related compounds, and their capacity to induce heme oxygenase 1 (HO-1) gene expression in U937 human monocytic cells, to activate upstream signaling pathways and to protect cells against menadione-induced oxidative stress. It was found that the electron-withdrawing (NO2, CN, halogen) groups in BMN molecules and double meta-MeO substituents increased the HO-1 gene induction, while the electron-donating groups in ortho/para position (OH, MeO and N-morpholino) significantly decreased it. The magnitude of activation of c-Jun, Nrf2, p38 MAPK, and p70S6K correlated with specific substitution patterns in the BMN structure. BMN-dependent maximal up-regulation of HO-1 required parallel increase in Nrf2 and phospho-c-Jun cellular levels. Liquid chromatography mass spectrometry (LC-MS) analysis revealed that BMNs can generate conjugates with one or two glutathione equivalent(s). This study supports the hypothesis that BMNs induce the expression of protective genes by alkylating sensitive cysteine residues of regulatory factors. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2011.05.028