(E)-N-(2-methoxy-5-(3-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-oxoprop-1-en-1-yl)phenyl)isobutyramide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (E)-N-(2-methoxy-5-(3-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-oxoprop-1-en-1-yl)phenyl)isobutyramide
• 英文别名: N-[2-methoxy-5-[(E)-3-(5-methoxy-2,2-dimethylchromen-8-yl)-3-oxoprop-1-enyl]phenyl]-2-methylpropanamide
• 化学式: C₂₆H₂₉NO₅
• 分子量: 435.52
• InChiKey: JPBJYGYQDZCXMG-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-methoxy-2-((2-methylbut-3-yn-2-yl)oxy)phenyl)ethanone 在 吡啶 、 4-二甲氨基吡啶 、 铁粉 、 氯化铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 49.0h， 生成 (E)-N-(2-methoxy-5-(3-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-oxoprop-1-en-1-yl)phenyl)isobutyramide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Millepachine Derivatives As a New Class of Tubulin Polymerization Inhibitors

  摘要：

  Twenty-one novel derivatives of millepachine were synthesized and evaluated for their in vitro antiprolifer-active activity. Among them, 8 exhibited the most potent activity, with IC50 values of 8-27 nM against panel of cancer cell lines and retained full activity in multidrug resistant cancer cells. Treated cells were arrested in G2/M phase and resulted in cellular apoptosis. Microtubule dynamics confirmed 8 was a novel tubulin. polymerization inhibitor by binding at the colchicine site 8 also exhibited antivascular activity because it concentration dependently reduced the cell migration and disrupted capillary like tube formation in HUVEC cells. Furthermore the hydrochloride salt of 8 (8 center dot HCl) significantly improved the bioavailability up to 47% while retaining the antiproliferative activity. Importantly, 8 center dot HCl significantly inhibited tumor growths in four xenograft models including resistance tumor-cell bearing mice models without causing significant loss of body weight, suggesting that 8 is a promising new orally anticancer agent to be developed.

  DOI：

  10.1021/jm500849z

文献信息

• (E)-1-(5-METHOXY-2,2-DIMETHYL-2H-CHROMEN-8-YL)-3-(4-METHOXYPHENYL)PROP-2-EN-1-ONE AND ANALOGS THEREOF, AS WELL AS PREPARATION METHOD AND USE THEREOF
  申请人：Chen Lijuan

  公开号：US20150133659A1

  公开（公告）日：2015-05-14

  The present invention relates to millepachine ((E)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-(4-methoxyphenyl)prop-2-en-1-one) and its analogues. The present invention provides methods for preparing these compounds, pharmaceutical compositions including these compounds, and methods of treating diseases utilizing pharmaceutical compositions including these compounds.

  本发明涉及米勒帕辛（（E）-1-(5-甲氧基-2,2-二甲基-2H-香豆素-8-基)-3-(4-甲氧基苯基)丙-2-烯-1-酮）及其类似物。本发明提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用包括这些化合物的药物组合物治疗疾病的方法。
• US9394268B2
  申请人：——

  公开号：US9394268B2

  公开（公告）日：2016-07-19
• Synthesis and Biological Evaluation of Novel Millepachine Derivatives As a New Class of Tubulin Polymerization Inhibitors
  作者：Zhuang Yang、Wenshuang Wu、Jingjing Wang、Li Liu、Luyuan Li、Jianhong Yang、Guangcheng Wang、Dong Cao、Ronghong Zhang、Minghai Tang、Jiaolin Wen、Jun Zhu、Wei Xiang、Fang Wang、Liang Ma、Mingli Xiang、Jingsong You、Lijuan Chen

  DOI：10.1021/jm500849z

  日期：2014.10.9

  Twenty-one novel derivatives of millepachine were synthesized and evaluated for their in vitro antiprolifer-active activity. Among them, 8 exhibited the most potent activity, with IC50 values of 8-27 nM against panel of cancer cell lines and retained full activity in multidrug resistant cancer cells. Treated cells were arrested in G2/M phase and resulted in cellular apoptosis. Microtubule dynamics confirmed 8 was a novel tubulin. polymerization inhibitor by binding at the colchicine site 8 also exhibited antivascular activity because it concentration dependently reduced the cell migration and disrupted capillary like tube formation in HUVEC cells. Furthermore the hydrochloride salt of 8 (8 center dot HCl) significantly improved the bioavailability up to 47% while retaining the antiproliferative activity. Importantly, 8 center dot HCl significantly inhibited tumor growths in four xenograft models including resistance tumor-cell bearing mice models without causing significant loss of body weight, suggesting that 8 is a promising new orally anticancer agent to be developed.