3-(3-benzyloxy-4-methoxyphenyl)-3-(pyrrol-1-yl)pyrrolidine propionamide | 679425-96-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(3-benzyloxy-4-methoxyphenyl)-3-(pyrrol-1-yl)pyrrolidine propionamide
• 英文别名: 3-(4-methoxy-3-phenylmethoxyphenyl)-1-pyrrolidin-1-yl-3-pyrrol-1-ylpropan-1-one
• CAS: 679425-96-8
• 化学式: C₂₅H₂₈N₂O₃
• 分子量: 404.509
• InChiKey: SXXKFOLDYRTTJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.68
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  43.7
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(3-benzyloxy-4-methoxyphenyl)-3-(pyrrol-1-yl)pyrrolidine propionamide 在 氢溴酸 、 溶剂黄146 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 3-(3-Hydroxy-4-methoxyphenyl)-2,3-dihydropyrrolizin-1-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z
• 作为产物：
  描述：

  异香兰素 在 乙酸铵 、 氯甲酸乙酯 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 丙酮 为溶剂， 反应 29.0h， 生成 3-(3-benzyloxy-4-methoxyphenyl)-3-(pyrrol-1-yl)pyrrolidine propionamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z