4-oxo-4-indole-cis-2-butenoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-oxo-4-indole-cis-2-butenoic acid
• 英文别名: (Z)-4-indol-1-yl-4-oxobut-2-enoic acid
• 化学式: C₁₂H₉NO₃
• 分子量: 215.208
• InChiKey: OCZKIRGOZAKDNV-WAYWQWQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  马来酸酐 、 吲哚 在 TEA 作用下， 以 乙腈 为溶剂， 以18%的产率得到4-oxo-4-indole-cis-2-butenoic acid
  参考文献：
  名称：

  Rational Design of an Indolebutanoic Acid Derivative as a Novel Aldose Reductase Inhibitor Based on Docking and 3D QSAR Studies of Phenethylamine Derivatives

  摘要：

  A series of 45 phenethylamine derivatives were synthesized and evaluated for their inhibitory activity against pig kidney aldose reductase (ALR2, EC 1.1.1.21). Their IC50 values ranged from 400 muM to 24 muM. The binding modes of compounds at the active site of ALR2 were examined using flexible docking. The results indicated that phenethylamine derivatives nicely fit into the active pocket of ALR2 by forming various hydrogen bonding and hydrophobic interactions. 3D-QSAR analysis was also conducted using FlexX-docked alignment of the compounds. The best prediction was obtained by CoMSIA combined with hydrophobic and hydrogen bond donor/acceptor field (q(2) = 0.557, r(2) = 0.934). A new derivative, 4-oxo-4-(4-hydroxyindole)butanoic acid, was designed, taking into account the CoMSIA field and the binding mode derived by FlexX docking. This rationally designed compound exhibits an ALR2 inhibition with an IC50 value of 7.4 muM, which compares favorably to that of a well-known ALR2 inhibitor, tolrestat (IC50 = 16 muM) and represents a potency approximately 240-fold higher than that of an original phenethylamine lead compound, YUA001.

  DOI：

  10.1021/jm0205346