(E)-2-cyano-3-(3-hydroxy-4-methoxyphenyl)acrylamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-2-cyano-3-(3-hydroxy-4-methoxyphenyl)acrylamide
• 英文别名: 2-cyano-3-(3-hydroxy-4-methoxyphenyl)propenamide；(E)-2-cyano-3-(3-hydroxy-4-methoxyphenyl)prop-2-enamide
• 化学式: C₁₁H₁₀N₂O₃
• 分子量: 218.212
• InChiKey: LDWQQGWNDMMORF-XBXARRHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  96.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  溶剂黄146 、 (E)-2-cyano-3-(3-hydroxy-4-methoxyphenyl)acrylamide 在 碘苯二乙酸 作用下， 反应 2.0h， 以30%的产率得到2-cyano-3-(2-acetoxy-5-hydroxy-4-methoxyphenyl)propenamide
  参考文献：
  名称：

  Structural Studies on Bioactive Compounds. 32. Oxidation of Tyrphostin Protein Tyrosine Kinase Inhibitors with Hypervalent Iodine Reagents

  摘要：

  Hydroxylated styrenes (tyrphostins) undergo oxidation by hypervalent iodine oxidants such as [(diacetoxy)iodo]benzene (DAIB) to give a range of products depending on the structure of the phenolic substrate, the solvent, the oxidant stoichiometry, and the purification strategy. Conditions have been developed to modify the phenolic component of the tyrphostin without affecting the appended substituted-vinyl moiety. Novel products include: unstable 2-acyloxy-2-methoxy-4-(substituted-vinyl)cyclohexadienones and their rearrangement products 2-acyloxy-4-hydroxy-3 -methoxy-1-(substituted-vinyl)benzenes; phenyliodoniophenolates and their rearrangement products iodophenoxytyrphostins; and 3,3'-dialkoxy-2,2'-dihydroxy-5,5'-di(substituted-vinyl)biphenyls. None of these oxidation products displayed enhanced activity in vitro in the NCI 60-cell line panel or in a panel of human breast cancer cell lines, compared to their tyrphostin precursors. The inhibitory activity of three representative tyrphostins (3e,n, 28) was not modulated by aerobic/anaerobic conditions in MCF-7 and MDA 468 cells and was independent of EGFR status in clones of ZR75B cells transfected with this receptor. Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-alpha, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autaphosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds. Growth stimulation by the tyrphostin 3n in the ER+ breast cell lines MCF-7, T47D, and ZR75-1 was abolished by 1 mu M tamoxifen, suggesting that this compound has estrogen agonist activity.

  DOI：

  10.1021/jm990947f
• 作为产物：
  描述：

  异香兰素 、 氰乙酰胺 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 (E)-2-cyano-3-(3-hydroxy-4-methoxyphenyl)acrylamide
  参考文献：
  名称：

  Structural Studies on Bioactive Compounds. 32. Oxidation of Tyrphostin Protein Tyrosine Kinase Inhibitors with Hypervalent Iodine Reagents

  摘要：

  Hydroxylated styrenes (tyrphostins) undergo oxidation by hypervalent iodine oxidants such as [(diacetoxy)iodo]benzene (DAIB) to give a range of products depending on the structure of the phenolic substrate, the solvent, the oxidant stoichiometry, and the purification strategy. Conditions have been developed to modify the phenolic component of the tyrphostin without affecting the appended substituted-vinyl moiety. Novel products include: unstable 2-acyloxy-2-methoxy-4-(substituted-vinyl)cyclohexadienones and their rearrangement products 2-acyloxy-4-hydroxy-3 -methoxy-1-(substituted-vinyl)benzenes; phenyliodoniophenolates and their rearrangement products iodophenoxytyrphostins; and 3,3'-dialkoxy-2,2'-dihydroxy-5,5'-di(substituted-vinyl)biphenyls. None of these oxidation products displayed enhanced activity in vitro in the NCI 60-cell line panel or in a panel of human breast cancer cell lines, compared to their tyrphostin precursors. The inhibitory activity of three representative tyrphostins (3e,n, 28) was not modulated by aerobic/anaerobic conditions in MCF-7 and MDA 468 cells and was independent of EGFR status in clones of ZR75B cells transfected with this receptor. Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-alpha, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autaphosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds. Growth stimulation by the tyrphostin 3n in the ER+ breast cell lines MCF-7, T47D, and ZR75-1 was abolished by 1 mu M tamoxifen, suggesting that this compound has estrogen agonist activity.

  DOI：

  10.1021/jm990947f

文献信息

• Structural Studies on Bioactive Compounds. 32. Oxidation of Tyrphostin Protein Tyrosine Kinase Inhibitors with Hypervalent Iodine Reagents
  作者：Geoffrey Wells、Angela Seaton、Malcolm F. G. Stevens

  DOI：10.1021/jm990947f

  日期：2000.4.1

  Hydroxylated styrenes (tyrphostins) undergo oxidation by hypervalent iodine oxidants such as [(diacetoxy)iodo]benzene (DAIB) to give a range of products depending on the structure of the phenolic substrate, the solvent, the oxidant stoichiometry, and the purification strategy. Conditions have been developed to modify the phenolic component of the tyrphostin without affecting the appended substituted-vinyl moiety. Novel products include: unstable 2-acyloxy-2-methoxy-4-(substituted-vinyl)cyclohexadienones and their rearrangement products 2-acyloxy-4-hydroxy-3 -methoxy-1-(substituted-vinyl)benzenes; phenyliodoniophenolates and their rearrangement products iodophenoxytyrphostins; and 3,3'-dialkoxy-2,2'-dihydroxy-5,5'-di(substituted-vinyl)biphenyls. None of these oxidation products displayed enhanced activity in vitro in the NCI 60-cell line panel or in a panel of human breast cancer cell lines, compared to their tyrphostin precursors. The inhibitory activity of three representative tyrphostins (3e,n, 28) was not modulated by aerobic/anaerobic conditions in MCF-7 and MDA 468 cells and was independent of EGFR status in clones of ZR75B cells transfected with this receptor. Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-alpha, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autaphosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds. Growth stimulation by the tyrphostin 3n in the ER+ breast cell lines MCF-7, T47D, and ZR75-1 was abolished by 1 mu M tamoxifen, suggesting that this compound has estrogen agonist activity.
• (E)-2-Cyano-3-(substituted phenyl)acrylamide analogs as potent inhibitors of tyrosinase: A linear β-phenyl-α,β-unsaturated carbonyl scaffold
  作者：Sujin Son、Haewon Kim、Hwi Young Yun、Do Hyun Kim、Sultan Ullah、Seong Jin Kim、Yeon-Jeong Kim、Min-Soo Kim、Jin-Wook Yoo、Pusoon Chun、Hyung Ryong Moon

  DOI：10.1016/j.bmc.2015.11.015

  日期：2015.12

  In this study, we synthesized (E)-2-cyano-3-(substituted phenyl) acrylamide (CPA) derivatives which possess a linear beta-phenyl-alpha,beta-unsaturated carbonyl scaffold and examined their inhibitory activities against tyrosinase. CPA analogs exerted inhibitory activity against mushroom tyrosinase. Results from the docking simulation indicated that CPA2 could bind directly to the active site of mushroom tyrosinase and the binding affinity of CPA2 for tyrosinase might be higher than that of kojic acid, a well-known potent tyrosinase inhibitor. In B16F10 cells, CPA2 significantly suppressed tyrosinase activity and melanogenesis in a dose-dependent manner. At the concentration of 25 mu M, CPA2 exhibited tyrosinase inhibitory activity comparable to that of kojic acid with no cytotoxic effect. Results from the present study suggest that CPA2 bearing a linear beta-phenyl-alpha,beta-unsaturated carbonyl scaffold may be the potential candidate for treatment of diseases associated with hyperpigmentation and that a linear beta-phenyl-alpha,beta-unsaturated carbonyl scaffold might be closely related to potent tyrosinase inhibition. (c) 2015 Elsevier Ltd. All rights reserved.