(2E,6E)-2,6-bis[(4-nitrophenyl)methylene]-4-hydroxycyclohexanone

• 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: (2E,6E)-2,6-bis[(4-nitrophenyl)methylene]-4-hydroxycyclohexanone
• 英文别名: (2E,6E)-2,6-bis(4'-nitrobenzylidene)-4-hydroxycyclohexanone；4-hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone；(2e,6e)-2,6-Bis(4'-nitrobenzylidene)-4-hydroxycyclohexanone；(2E,6E)-4-hydroxy-2,6-bis[(4-nitrophenyl)methylidene]cyclohexan-1-one
• 化学式: C₂₀H₁₆N₂O₆
• 分子量: 380.357
• InChiKey: BCDOATJLGCTQBE-KAVGSWPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-二琥珀酰亚胺基碳酸酯 、 (2E,6E)-2,6-bis[(4-nitrophenyl)methylene]-4-hydroxycyclohexanone 在 吡啶 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 18.0h， 以75%的产率得到(3E,5E)-3,5-bis[(4-nitrophenyl)methylene]-4-oxocyclohexyl 2,5-dioxo-1-pyrrolidinyl carbonate
  参考文献：
  名称：

  Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent

  摘要：

  Bis-arylidenecycloalkanones structurally related to the nonselective isopeptidase inhibitor G5 were synthesized and tested for cytotoxic activity against glioblastoma cells. Cytotoxicities correlate well with Hammett s constants for substituted arylidene groups, confirming the proposed inhibition mechanism. A new inhibitor (2c) based on the 4-hydroxycyclohexanone scaffold, which favors apoptosis over necrosis, was selected for further development. 2c inhibited representative deubiquitinases with micromolar IC50, and its proapoptotic activity was studied on several cancer cell lines. Inhibitor 2c was conjugated to PEG via dicarbamate and diester linkers. While the dicarbamate was inactive, the diester (2cPE) behaves like a prodrug and is converted into the active species 2c by secreted esterase activities. Finally, 2cPE was also tested in vivo on A549 lung carcinoma xenografts generated in mice. Intravenous treatment with 2cPE led to a significant reduction in primary tumor growth, without appreciable toxicity to mice.

  DOI：

  10.1021/jm501336h
• 作为产物：
  描述：

  4-羟基环己酮 、 对硝基苯甲醛 在 硫酸 、 溶剂黄146 作用下， 以85%的产率得到(2E,6E)-2,6-bis[(4-nitrophenyl)methylene]-4-hydroxycyclohexanone
  参考文献：
  名称：

  C 5-姜黄素的新型簇 ：设计，合成，体外抗增殖活性和基于4-羟基环己酮支架的双（亚芳基）-4-环酮衍生物的DNA结合

  摘要：

  本文描述了一个新的系列（ 6 ）C 5-姜黄素衍生物（2 E ，6 E- 2,2,6- 二亚苄基-4-羟基环己酮），并对其体外抗增殖活性进行了评估。进行了针对人A2780（卵巢），C33A（子宫颈）和MDA-MB-231（乳腺癌）癌细胞系的31种化合物的评估，以获得结构活性相关数据。表现最佳的是（2 E ，6 E ）-2,6-双（3'-硝基亚苄基）-4-羟基环己酮（ 6h ），IC 50分别为1.30μM，3.69μM和19.13μM的顺铂，分别为0.68μM（A2780），0.69μM（C33A）和0.92μM（MDA-MB-231）。根据计算的理化性质，第 6列中的 某些成员 ，即（2 E ，6 E ）-2,6-双[（4'-吡啶基）亚甲基] -4-羟基环己酮（ 6p ）[IC 50  = 0.76μM（A2780） ，2.69μM（C33A），1.28μM（MDA-MB-231）]与姜黄素相比似乎具有更高的生物利用度。系列

  DOI：

  10.1007/s11164-019-03859-4

文献信息

• 10.3390/pharmaceutics16050664
  作者：Maddaloni, Marianna、Farra, Rossella、Dapas, Barbara、Felluga, Fulvia、Benedetti, Fabio、Berti, Federico、Drioli, Sara、Vidali, Mattia、Cemazar, Maja、Kamensek, Urska、Brancolini, Claudio、Murano, Erminio、Maremonti, Francesca、Grassi, Mario、Biasin, Alice、Rizzolio, Flavio、Cavarzerani, Enrico、Scaggiante, Bruna、Bulla, Roberta、Balduit, Andrea、Ricci, Giuseppe、Zito, Gabriella、Romano, Federico、Bonin, Serena、Azzalini, Eros、Baj, Gabriele、Tierno, Domenico、Grassi, Gabriele

  DOI：10.3390/pharmaceutics16050664

  日期：——
• A novel cluster of C5-curcuminoids: design, synthesis, in vitro antiproliferative activity and DNA binding of bis(arylidene)-4-cyclanone derivatives based on 4-hydroxycyclohexanone scaffold
  作者：Imre Huber、István Zupkó、András Gyovai、Péter Horváth、Eszter Kiss、Gergely Gulyás-Fekete、János Schmidt、Pál Perjési

  DOI：10.1007/s11164-019-03859-4

  日期：2019.9

  of C5-curcuminoid derivatives (2 E ,6 E- 2,6-dibenzylidene-4-hydroxycyclohexanones) is described here with their evaluation for in vitro antiproliferative activities. Evaluation of 31 compounds against human A2780 (ovarian), C33A (cervix) and MDA-MB-231 (breast) cancer cell lines was performed to obtain structure activity relation data. The best performer was (2 E ,6 E )-2,6-bis(3′-nitrobenzylidene

  本文描述了一个新的系列（ 6 ）C 5-姜黄素衍生物（2 E ，6 E- 2,2,6- 二亚苄基-4-羟基环己酮），并对其体外抗增殖活性进行了评估。进行了针对人A2780（卵巢），C33A（子宫颈）和MDA-MB-231（乳腺癌）癌细胞系的31种化合物的评估，以获得结构活性相关数据。表现最佳的是（2 E ，6 E ）-2,6-双（3'-硝基亚苄基）-4-羟基环己酮（ 6h ），IC 50分别为1.30μM，3.69μM和19.13μM的顺铂，分别为0.68μM（A2780），0.69μM（C33A）和0.92μM（MDA-MB-231）。根据计算的理化性质，第 6列中的 某些成员 ，即（2 E ，6 E ）-2,6-双[（4'-吡啶基）亚甲基] -4-羟基环己酮（ 6p ）[IC 50  = 0.76μM（A2780） ，2.69μM（C33A），1.28μM（MDA-MB-231）]与姜黄素相比似乎具有更高的生物利用度。系列
• Synthesis, Characterization, and Optimization for in Vivo Delivery of a Nonselective Isopeptidase Inhibitor as New Antineoplastic Agent
  作者：Ulma Cersosimo、Andrea Sgorbissa、Carmen Foti、Sara Drioli、Rosario Angelica、Andrea Tomasella、Raffaella Picco、Marta Stefania Semrau、Paola Storici、Fabio Benedetti、Federico Berti、Claudio Brancolini

  DOI：10.1021/jm501336h

  日期：2015.2.26

  Bis-arylidenecycloalkanones structurally related to the nonselective isopeptidase inhibitor G5 were synthesized and tested for cytotoxic activity against glioblastoma cells. Cytotoxicities correlate well with Hammett s constants for substituted arylidene groups, confirming the proposed inhibition mechanism. A new inhibitor (2c) based on the 4-hydroxycyclohexanone scaffold, which favors apoptosis over necrosis, was selected for further development. 2c inhibited representative deubiquitinases with micromolar IC50, and its proapoptotic activity was studied on several cancer cell lines. Inhibitor 2c was conjugated to PEG via dicarbamate and diester linkers. While the dicarbamate was inactive, the diester (2cPE) behaves like a prodrug and is converted into the active species 2c by secreted esterase activities. Finally, 2cPE was also tested in vivo on A549 lung carcinoma xenografts generated in mice. Intravenous treatment with 2cPE led to a significant reduction in primary tumor growth, without appreciable toxicity to mice.