4-((E)-2-(5-((E)-4-butoxy-3-methoxystyryl)-1H-pyrazol-3-yl)vinyl)-2-methoxyphenol | 1346004-21-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 4-((E)-2-(5-((E)-4-butoxy-3-methoxystyryl)-1H-pyrazol-3-yl)vinyl)-2-methoxyphenol
• 英文别名: 4-[(E)-2-[3-[(E)-2-(4-butoxy-3-methoxyphenyl)ethenyl]-1H-pyrazol-5-yl]ethenyl]-2-methoxyphenol
• CAS: 1346004-21-4
• 化学式: C₂₅H₂₈N₂O₄
• 分子量: 420.508
• InChiKey: JDPMFNCGWIHFRK-JMQWPVDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  76.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  正溴丁烷 、 hydrazinocurcumin 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以57%的产率得到4-((E)-2-(5-((E)-4-butoxy-3-methoxystyryl)-1H-pyrazol-3-yl)vinyl)-2-methoxyphenol
  参考文献：
  名称：

  Binding of isoxazole and pyrazole derivatives of curcumin with the activator binding domain of novel protein kinase C

  摘要：

  The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target because of its involvement in the regulation of various cellular functions, including cell growth, differentiation, metabolism, and apoptosis. The endogenous PKC activator diacylglycerol contains two long carbon chains, which are attached to the glycerol moiety via ester linkage. Natural product curcumin (1), the active constituent of Curcuma L., contains two carbonyl and two hydroxyl groups. It modulates PKC activity and binds to the activator binding site (Majhi et al., Bioorg. Med. Chem. 2010, 18, 1591). To investigate the role of the carbonyl and hydroxyl groups of curcumin in PKC binding and to develop curcumin derivatives as effective PKC modulators, we synthesized several isoxazole and pyrazole derivatives of curcumin (2-6), characterized their absorption and fluorescence properties, and studied their interaction with the activator-binding second cysteine-rich C1B subdomain of PKC delta, PKC epsilon and PKC theta. The EC(50)s of the curcumin derivatives for protein fluorescence quenching varied in the range of 3-25 mu M. All the derivatives showed higher binding with the PKC theta C1B compared with PKC delta C1B and PKC epsilon C1B. Fluorescence emission maxima of 2-5 were blue shifted in the presence of the C1B domains, confirming their binding to the protein. Molecular docking revealed that hydroxyl, carbonyl and pyrazole ring of curcumin (1), pyrazole (2), and isoxazole (4) derivatives form hydrogen bonds with the protein residues. The present result shows that isoxazole and pyrazole derivatives bind to the activator binding site of novel PKCs and both carbonyl and hydroxy groups of curcumin play roles in the binding process, depending on the nature of curcumin derivative and the PKC isotype used. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.011