[3,5-Bis(3,4-dihydroxybenzylidene)-4-oxocyclohexyl]acetic acid

• 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: [3,5-Bis(3,4-dihydroxybenzylidene)-4-oxocyclohexyl]acetic acid
• 英文别名: 2-[(3E,5E)-3,5-bis[(3,4-dihydroxyphenyl)methylidene]-4-oxocyclohexyl]acetic acid
• 化学式: C₂₂H₂₀O₇
• 分子量: 396.397
• InChiKey: JLLKDSXQWKZGDX-IAGONARPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  135
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(4-氧代环己基)乙酸 、 3,4-二羟基苯甲醛 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 1.5h， 以55%的产率得到[3,5-Bis(3,4-dihydroxybenzylidene)-4-oxocyclohexyl]acetic acid
  参考文献：
  名称：

  2,6-Bis(3,4,5-trihydroxybenzylydene) derivatives of cyclohexanone

  摘要：

  A number of 2,6-bisbenzylidenecyclohexane-1-one derivatives have been synthesized and tested as HIV-1 integrase (IN) inhibitors with the aim of obtaining compounds capable to elicit antiviral activity at non-cytotoxic concentrations in cell-based assays. 3,5-Bis(3,4,5-trihydroxybenzylidene)-4-oxocyclohexaneacetic acid (20d) resulted one of the most potent and selective derivatives in acutely infected MT-4 cells (EC50 and CC50 values of 2 and 40 muM, respectively). In enzyme assays with recombinant HIV-1 integrase (rIN), this compound proved able to inhibit both 3'-processing and disintegration with IC50 values of 0.2 and 0.5 muM, respectively. In order to develop a model capable to predict the anti HIV-IN activity and useful to design novel derivatives, we performed a comparative molecular field analysis (CoMFA) like 3-D-QSAR. In our model the ligands were described quantitatively in the GRID program, and the model was optimized by selecting only the most informative variables in the GOLPE program. We found the predictive ability of the model to increase significantly when the number of variables was reduced from 20,925 to 1327. A Q(2) of 0.73 was obtained with the final model, confirming the predictive ability of the model. By studying the PLS coefficients in informative 3-D contour plots, ideas for the synthesis of new compounds could be generated. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.005