3,5-Bis(4-hydroxy-3-nitrobenzylidene)piperidin-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3,5-Bis(4-hydroxy-3-nitrobenzylidene)piperidin-4-one
• 英文别名: (3E,5E)-3,5-bis[(4-hydroxy-3-nitrophenyl)methylidene]piperidin-4-one
• 化学式: C₁₉H₁₅N₃O₇
• 分子量: 397.344
• InChiKey: YHPWRQPORKRTMM-ACFHMISVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-羟基-3-硝基苯甲醛 、 4-氧代哌啶酮盐酸盐 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 18.25h， 以35%的产率得到3,5-Bis(4-hydroxy-3-nitrobenzylidene)piperidin-4-one
  参考文献：
  名称：

  Synthesis, cytotoxicity, and structure–activity insight of NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidones

  摘要：

  Twenty-one NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidone analogs of curcumin, 12 of which are novel, were synthesized and evaluated for their cytotoxicity against B16 (murine melanoma) and L1210 (murine lymphoma) cells grown in culture. These curcumin analogs are related to a known anticancer STAT3 inhibitor 3,5-bis-(4-fluorobenzyl)-4-piperidone (3). The compounds showed remarkable cytotoxicity, especially against B16 cells. The dimethoxy substituted analogs 4e and 4f and dihydroxy analog 4i emerged as the most active compounds with IC50 values in the range of 0.2-2.3 mu M. 4e, f, and i were about 10-times more cytotoxic against both cell lines than 3. Analysis of the results demonstrates that the position of the hydroxyl group is crucial for cytotoxicity. Amino-containing analogs are generally less active than their halogenated and oxygen-containing analogs, and N-substitution in the 4-piperidone moiety adds value to the cytotoxicity of the compounds.

  DOI：

  10.1007/s00044-013-0557-9

文献信息

• 2,6-Bis(3,4,5-trihydroxybenzylydene) derivatives of cyclohexanone
  作者：Roberta Costi、Roberto Di Santo、Marino Artico、Silvio Massa、Rino Ragno、Roberta Loddo、Massimiliano La Colla、Enzo Tramontano、Paolo La Colla、Alessandra Pani

  DOI：10.1016/j.bmc.2003.10.005

  日期：2004.1

  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.
• Synthesis, cytotoxicity, and structure–activity insight of NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidones
  作者：Matthew Gregory、Armaan Dandavati、Megan Lee、Samuel Tzou、Mia Savagian、Kimberly A. Brien、Vijay Satam、Pravin Patil、Moses Lee

  DOI：10.1007/s00044-013-0557-9

  日期：2013.11

  Twenty-one NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidone analogs of curcumin, 12 of which are novel, were synthesized and evaluated for their cytotoxicity against B16 (murine melanoma) and L1210 (murine lymphoma) cells grown in culture. These curcumin analogs are related to a known anticancer STAT3 inhibitor 3,5-bis-(4-fluorobenzyl)-4-piperidone (3). The compounds showed remarkable cytotoxicity, especially against B16 cells. The dimethoxy substituted analogs 4e and 4f and dihydroxy analog 4i emerged as the most active compounds with IC50 values in the range of 0.2-2.3 mu M. 4e, f, and i were about 10-times more cytotoxic against both cell lines than 3. Analysis of the results demonstrates that the position of the hydroxyl group is crucial for cytotoxicity. Amino-containing analogs are generally less active than their halogenated and oxygen-containing analogs, and N-substitution in the 4-piperidone moiety adds value to the cytotoxicity of the compounds.