2-(4-methoxyphenyl)-3-oxo-3-(3,4,5-trimethoxyphenyl)propanenitrile | 1025917-50-3

• 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: 2-(4-methoxyphenyl)-3-oxo-3-(3,4,5-trimethoxyphenyl)propanenitrile
• CAS: 1025917-50-3
• 化学式: C₁₉H₁₉NO₅
• 分子量: 341.364
• InChiKey: ITXWNGCYHJQWFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  77.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-3-oxo-3-(3,4,5-trimethoxyphenyl)propanenitrile 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以13%的产率得到3-(3,4,5-trimethoxyphenyl)-4-(4-methoxyphenyl)-5-isoxazolamine
  参考文献：
  名称：

  3-（5-）-氨基-邻-二芳基异唑类：区域选择性合成和抗微管蛋白活性

  摘要：

  已经验证了被聚烷氧基芳基药效基团取代的5-氨基-和3-氨基二芳基异恶唑的区域选择性合成。合成方案的起始原料很容易从植物提取物中获得。在表型海胆胚胎试验中进一步测试了目标分子，以鉴定具有抗有丝分裂微管去稳定活性的化合物。结构与活性之间的关系研究表明，有效的抗增殖活性必不可少的结构特征包括：1）5-氨基异恶唑桥联双芳基取代基（环A和B）；2）未取代的5-氨基；3）3,4,5-甲氧基取代的苯和4-甲氧基苯的药效基团分别作为环A和B。

  DOI：

  10.1016/j.ejmech.2013.12.006
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酸 在 氯化亚砜 、 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 1.5h， 生成 2-(4-methoxyphenyl)-3-oxo-3-(3,4,5-trimethoxyphenyl)propanenitrile
  参考文献：
  名称：

  cis-Restricted 3-Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays

  摘要：

  We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multidrug-resistant cancer cells.

  DOI：

  10.1021/np400310m

文献信息

• Synthesis and biological evaluation of 3,4-diaryl-5-aminoisoxazole derivatives
  作者：Tao Liu、Xiaowu Dong、Na Xue、Rui Wu、Qiaojun He、Bo Yang、Yongzhou Hu

  DOI：10.1016/j.bmc.2009.07.040

  日期：2009.9.1

  A series of cis-restricted 3,4-diaryl-5-aminoisoxazoles have been synthesized and evaluated for their biological activities. Among them, compound 11a and 13a displayed potent cytotoxic activities in vitro against five human cancer cell lines with IC50 values in the low micromolar range and two compounds inhibited tubulin polymerization with IC50 value of 1.8, and 2.1 mu M, respectively, similar to that of CA-4. Compound 13a could arrest at the G2/M phase of the cell cycle at the concentration of 0.1 and 1.0 mu M and induce apoptosis at 0.1-1.0 mu M. (C) 2009 Elsevier Ltd. All rights reserved.
• 4,5‐Diaryl‐3‐aminopyrazole Derivatives as Analogs of Combretastatin A‐4: Synthesis and Biological Evaluation
  作者：Tao Liu、Rong Cui、Jing Chen、Jun Zhang、Qiaojun He、Bo Yang、Yongzhou Hu

  DOI：10.1002/ardp.201000069

  日期：2011.5

  A series of cis‐restricted 4,5‐diaryl‐3‐aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA‐109, A549, SMMC‐7721, and PC‐3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G2/M phase. The docking research showed the conformation of 5a overlaps well with CA‐4 in the crystallized protein complex, suggesting the 4,5‐diaryl‐3‐aminopyrazoles were good mimics of CA‐4.