(E)-3-(3-amino-4-methoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one

• 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)-3-(3-amino-4-methoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one
• 英文别名: E-3-(3-azanyl-4-methoxy-phenyl)-1-(5-methoxy-2,2-dimethyl-chromen-8-yl)prop-2-en-1-one；(E)-3-(3-amino-4-methoxyphenyl)-1-(5-methoxy-2,2-dimethylchromen-8-yl)prop-2-en-1-one
• 化学式: C₂₂H₂₃NO₄
• 分子量: 365.429
• InChiKey: IUIOXMRMRADSKI-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-amino-4-methoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 (E)-6-((2-methoxy-5-(3-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-oxoprop-1-en-1-yl)phenyl)amino)-6-oxohexanoic acid
  参考文献：
  名称：

  Dual-targeting antitumor hybrids derived from Pt(IV) species and millepachine analogues

  摘要：

  Many strategies have been developed to circumvent the shortcomings of Pt(II)-based chemotherapy, but the inherent problems still have not been effectively resolved. Here we report a new series of dual targeting Pt(IV) prodrugs, conjugates of millepachine analogues with the related Pt(IV) complexes derived from cisplatin or oxaliplatin, respectively, which can inhibit tubulin polymerization and induce DNA damage. Among them, compound 19 possessed excellent antitumor activities against the tested human cancer cell lines, and arrested the cell cycle at the G2/M phases and ultimately induced cell apoptosis. Interestingly, its low cytotoxicity toward two human normal cells and sensitivity toward two cisplatin-resistant cells revealed the possibility for cancer therapy. More importantly, 19 displayed excellent antitumor efficacy in the SK-OV-3 xenograft model better than cisplatin and the corresponding millepachine analogue. Our research provided an efficient strategy for multi-targeting antitumor drug development. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.012
• 作为产物：
  描述：

  1-(4-methoxy-2-((2-methylbut-3-yn-2-yl)oxy)phenyl)ethanone 在 吡啶 、 铁粉 、 氯化铵 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 37.0h， 生成 (E)-3-(3-amino-4-methoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)prop-2-en-1-one
  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。
• 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.
• US9394268B2
  申请人：——

  公开号：US9394268B2

  公开（公告）日：2016-07-19
• Dual-targeting antitumor hybrids derived from Pt(IV) species and millepachine analogues
  作者：Xiaochao Huang、Shixian Hua、Rizhen Huang、Zhikun Liu、Shaohua Gou、Zhimei Wang、Zhixin Liao、Hengshan Wang

  DOI：10.1016/j.ejmech.2018.02.012

  日期：2018.3

  Many strategies have been developed to circumvent the shortcomings of Pt(II)-based chemotherapy, but the inherent problems still have not been effectively resolved. Here we report a new series of dual targeting Pt(IV) prodrugs, conjugates of millepachine analogues with the related Pt(IV) complexes derived from cisplatin or oxaliplatin, respectively, which can inhibit tubulin polymerization and induce DNA damage. Among them, compound 19 possessed excellent antitumor activities against the tested human cancer cell lines, and arrested the cell cycle at the G2/M phases and ultimately induced cell apoptosis. Interestingly, its low cytotoxicity toward two human normal cells and sensitivity toward two cisplatin-resistant cells revealed the possibility for cancer therapy. More importantly, 19 displayed excellent antitumor efficacy in the SK-OV-3 xenograft model better than cisplatin and the corresponding millepachine analogue. Our research provided an efficient strategy for multi-targeting antitumor drug development. (C) 2018 Elsevier Masson SAS. All rights reserved.