1-(naphthalen-2-yl)-2-(3,4,5-trimethoxyphenyl) ethane-1,2-dione | 850035-93-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(naphthalen-2-yl)-2-(3,4,5-trimethoxyphenyl) ethane-1,2-dione
• 英文别名: 1-Naphthalen-2-yl-2-(3,4,5-trimethoxy-phenyl)-ethane-1,2-dione；1-naphthalen-2-yl-2-(3,4,5-trimethoxyphenyl)ethane-1,2-dione
• CAS: 850035-93-7
• 化学式: C₂₁H₁₈O₅
• 分子量: 350.371
• InChiKey: PDSNSFKAXVSMPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(naphthalen-2-yl)-2-(3,4,5-trimethoxyphenyl) ethane-1,2-dione 在 吡啶 、 selenium(IV) oxide 、 盐酸羟胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 3-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1,2,5-selenadiazole
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 3,4-diaryl-1,2,5-selenadiazol analogues of combretastatin A-4

  摘要：

  A set of novel selenium-containing heterocyclic analogues of combretastatin A-4 (CA-4) have been designed and synthesised using a rigid 1,2,5-selenadiazole as a linker to fix the cis-orientation of ring-A and ring-B. All of the target compounds were evaluated for their in vitro anti-proliferative activities. Among these compounds, compounds 3a, 3i, 3n and 3q exhibited superior potency against different tumour cell lines with IC50 values at the nanomolar level. Moreover, compound 3n significantly induced cell cycle arrest in the G(2)/M phase, inhibited tubulin polymerisation into microtubules and caused microtubule destabilisation. A molecular modelling study of compound 3n was performed to elucidate its binding mode at the colchicine site in the tubulin dimer and to provide a basis for the further structure-guided design of novel CA-4 analogues. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.046
• 作为产物：
  描述：

  dimethyl α-hydroxy-α-(3,4,5-trimethoxyphenyl)methanephosphonate 在 selenium(IV) oxide 、 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二甲基亚砜 、 甲苯 为溶剂， 反应 0.03h， 生成 1-(naphthalen-2-yl)-2-(3,4,5-trimethoxyphenyl) ethane-1,2-dione
  参考文献：
  名称：

  3,4-二芳基-1,2,5-恶二唑-2 / 5-氧化物作为微管蛋白聚合的高效抑制剂的设计，合成和生物学评估

  摘要：

  研究了康布雷他汀A-4（CA-4）的刚性类似物的结构活性关系，从而发现了一系列3,4-二芳基-1,2,5-恶二唑-N-氧化物。其中，7n'和7n''在纳摩尔浓度下对三种癌细胞显示出显着的抗增殖活性。有趣的是，7n'比CA-4更有效地抑制微管蛋白聚合。细胞机制研究阐明了7n'破坏了细胞微管结构，使细胞周期停滞在G 2 / M期并诱导了细胞凋亡。分子建模研究显示1,2,5-恶二唑-N-氧化环可增加与结合位点的氢键相互作用。这些结果为开发新的CA-4类似物提供了动力和进一步的指导。

  DOI：

  10.1016/j.ejmech.2019.05.036

文献信息

• New naphthylcombretastatins. Modifications on the ethylene bridge
  作者：Ana B. Sánchez Maya、Concepción Pérez-Melero、Nélida Salvador、Rafael Peláez、Esther Caballero、Manuel Medarde

  DOI：10.1016/j.bmc.2005.01.012

  日期：2005.3

  Compounds with three aromatic systems, carrying a 2-naphthalene and a 3,4,5-trimethoxyphenyl moieties bonded to five-membered, six-membered or fused heterocycles display potent cytotoxic effect and inhibition of tubulin polymerization, in agreement with their structural similarity to combretastatins and their heterocyclic analogues. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and antitumor activity of benzils related to combretastatin A-4
  作者：Céline Mousset、Anne Giraud、Olivier Provot、Abdallah Hamze、Jérôme Bignon、Jian-Miao Liu、Sylviane Thoret、Joëlle Dubois、Jean-Daniel Brion、Mouâd Alami

  DOI：10.1016/j.bmcl.2008.04.053

  日期：2008.6

  A series of benzil derivatives related to combretastatin A-4 (CA-4) have been synthesized by oxidation of diarylalkynes promoted by PdI2 in DMSO. Using this new protocol, 14 benzils were prepared in good to excellent yields and their biological activity has been delineated. Several benzils exhibited excellent antiproliferative activity: for example, 4j and 4k bearing the greatest resemblance to CA-4 and AVE-8062, respectively, were found to inhibit cell growth at the nanomolar level (20-50 nM) on four human tumor cell lines. Flow cytometric analysis indicates that these compounds act as antimitotics and arrest the cell cycle in G(2)/M phase. A cell-based assay indicated that compounds 4j and 4k displayed a similar inhibition of tubulin assembly with an IC50 value similar to CA-4. These results clearly demonstrated that the Z-double bond of CA-4 can be replaced by a 1,2-diketone unit without significant loss of cytotoxicity and inhibition of tubulin assembly potency. (C) 2008 Elsevier Ltd. All rights reserved.
• Design, synthesis and biological evaluation of 3,4-diaryl-1,2,5-oxadiazole-2/5-oxides as highly potent inhibitors of tubulin polymerization
  作者：Yilang Hong、Yinglin Zhao、Lei Yang、Minghuan Gao、Long Li、Shuai Man、Zhan Wang、Qi Guan、Kai Bao、Daiying Zuo、Yingliang Wu、Weige Zhang

  DOI：10.1016/j.ejmech.2019.05.036

  日期：2019.9

  4-diaryl-1,2,5-oxadiazole-N-oxides. Among them, 7n′ and 7n′′ showed remarkable antiproliferative activities against three cancer cell lines in nanomolar concentrations. Interestingly, 7n′ inhibited tubulin polymerization much more efficiently than CA-4. Cellular mechanism investigation elucidated 7n′ disrupted the cellular microtubule structure, arrested cell cycle at G2/M phase and induces apoptosis. Molecular

  研究了康布雷他汀A-4（CA-4）的刚性类似物的结构活性关系，从而发现了一系列3,4-二芳基-1,2,5-恶二唑-N-氧化物。其中，7n'和7n''在纳摩尔浓度下对三种癌细胞显示出显着的抗增殖活性。有趣的是，7n'比CA-4更有效地抑制微管蛋白聚合。细胞机制研究阐明了7n'破坏了细胞微管结构，使细胞周期停滞在G 2 / M期并诱导了细胞凋亡。分子建模研究显示1,2,5-恶二唑-N-氧化环可增加与结合位点的氢键相互作用。这些结果为开发新的CA-4类似物提供了动力和进一步的指导。
• Synthesis and biological evaluation of novel 3,4-diaryl-1,2,5-selenadiazol analogues of combretastatin A-4
  作者：Qi Guan、Fushan Yang、Dandan Guo、Jingwen Xu、Mingyang Jiang、Chunjiang Liu、Kai Bao、Yingliang Wu、Weige Zhang

  DOI：10.1016/j.ejmech.2014.09.046

  日期：2014.11

  A set of novel selenium-containing heterocyclic analogues of combretastatin A-4 (CA-4) have been designed and synthesised using a rigid 1,2,5-selenadiazole as a linker to fix the cis-orientation of ring-A and ring-B. All of the target compounds were evaluated for their in vitro anti-proliferative activities. Among these compounds, compounds 3a, 3i, 3n and 3q exhibited superior potency against different tumour cell lines with IC50 values at the nanomolar level. Moreover, compound 3n significantly induced cell cycle arrest in the G(2)/M phase, inhibited tubulin polymerisation into microtubules and caused microtubule destabilisation. A molecular modelling study of compound 3n was performed to elucidate its binding mode at the colchicine site in the tubulin dimer and to provide a basis for the further structure-guided design of novel CA-4 analogues. (C) 2014 Elsevier Masson SAS. All rights reserved.