3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one

• 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: 3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one
• 英文别名: (3R,4S)-3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one
• 化学式: C₂₇H₂₉NO₇
• 分子量: 479.53
• InChiKey: CRBBNFROHMFUPS-JWQCQUIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (4-methoxybenzylidene)-3,4,5-trimethoxyphenylamine 、 (3,4-二甲氧基苯基)乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以1.1%的产率得到3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one
  参考文献：
  名称：

  Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents

  摘要：

  The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (beta-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the beta-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46 and 47 displayed the most potent antiproliferative activity of the series. beta-Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells (IC50 = 0.8 nM) together with significant in vitro inhibition of tubulin polymerization and has been selected for further biochemical assessment. These novel beta-lactam compounds are identified as potentially useful scaffolds for the further development of antitumor agents that target tubulin.

  DOI：

  10.1021/jm101115u

文献信息

• Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents
  作者：Niamh M. O’Boyle、Miriam Carr、Lisa M. Greene、Orla Bergin、Seema M. Nathwani、Thomas McCabe、David G. Lloyd、Daniela M Zisterer、Mary J. Meegan

  DOI：10.1021/jm101115u

  日期：2010.12.23

  The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (beta-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the beta-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46 and 47 displayed the most potent antiproliferative activity of the series. beta-Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells (IC50 = 0.8 nM) together with significant in vitro inhibition of tubulin polymerization and has been selected for further biochemical assessment. These novel beta-lactam compounds are identified as potentially useful scaffolds for the further development of antitumor agents that target tubulin.