4-(3,4-dimethoxyphenyl)-3-(pyrrol-1-yl)-1H-pyrrole-2-pyrrolidine carboxamide | 679426-06-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-(3,4-dimethoxyphenyl)-3-(pyrrol-1-yl)-1H-pyrrole-2-pyrrolidine carboxamide
• 英文别名: 4'-(3,4-dimethoxyphenyl)-2'-(pyrrolidin-1-ylcarbonyl)-1'H-1,3'-bipyrrole；[4-(3,4-dimethoxyphenyl)-3-pyrrol-1-yl-1H-pyrrol-2-yl]-pyrrolidin-1-ylmethanone
• CAS: 679426-06-3
• 化学式: C₂₁H₂₃N₃O₃
• 分子量: 365.432
• InChiKey: SKDPXRHVPTWUEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.73
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  59.49
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(3,4-dimethoxyphenyl)-3-(pyrrol-1-yl)-1H-pyrrole-2-pyrrolidine carboxamide 在 三氯氧磷 、 sodium hydroxide 作用下， 以30%的产率得到3-(3,4-dimethoxyphenyl)pyrrolo[2,3-b]pyrrolizin-8(1H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pyrrolopyrrolizinones as anticancer agents

  摘要：

  We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin-8(1H)-ones starting from commercial (het)aryl-acetonitriles. A more convergent route was also described through the first synthesis of ethyl 3-amino-4-bromo-1H-pyrrole-2-carboxylate 17. The antiproliferative activities of these compounds were tested toward various cell lines and one of them 10k shows interesting cytotoxic properties, although it was less potent than our lead compound in thiophene series 1k. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.022
• 作为产物：
  描述：

  methyl 3-amino-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylate 在 4-氯吡啶盐酸盐 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(3,4-dimethoxyphenyl)-3-(pyrrol-1-yl)-1H-pyrrole-2-pyrrolidine carboxamide
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pyrrolopyrrolizinones as anticancer agents

  摘要：

  We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin-8(1H)-ones starting from commercial (het)aryl-acetonitriles. A more convergent route was also described through the first synthesis of ethyl 3-amino-4-bromo-1H-pyrrole-2-carboxylate 17. The antiproliferative activities of these compounds were tested toward various cell lines and one of them 10k shows interesting cytotoxic properties, although it was less potent than our lead compound in thiophene series 1k. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.022

文献信息

• Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents
  作者：Vincent Lisowski、Stéphane Léonce、Laurence Kraus-Berthier、Jana Sopková-de Oliveira Santos、Alain Pierré、Ghanem Atassi、Daniel-Henri Caignard、Pierre Renard、Sylvain Rault

  DOI：10.1021/jm030961z

  日期：2004.3.1

  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.