(11aS)-8-[3-(1H-2-indolycarboxamido)]butoxyl-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (11aS)-8-[3-(1H-2-indolycarboxamido)]butoxyl-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one
• 英文别名: N-[4-[[(6aS)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]butyl]-1H-indole-2-carboxamide
• 化学式: C₂₆H₂₈N₄O₄
• 分子量: 460.533
• InChiKey: BQFHQEUKXWUMSR-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吲哚-2-羧酸 在 四溴化碳 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 51.5h， 生成 (11aS)-8-[3-(1H-2-indolycarboxamido)]butoxyl-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Pyrrolo[2,1-c][1,4]benzodiazepine and Indole Conjugates as Anticancer Agents

  摘要：

  A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) hybrids linked with indole carboxylates is described. These compounds were prepared by linking C-8 of 3 (DC-81) with an indole 2-carbonyl moiety (9) through carbon chain linkers to afford PBD hybrid agents 17-21 in good yields. Preliminary in vivo tests show that these hybrid agents have potent antitumor activity. The cytotoxic studies of the hybrid agents on human melanoma A2058 cells indicate most of the hybrids induced higher cytotoxicity, better DNA-binding ability, an increase in the apoptotic sub-G1 population, and a significant reduction in Delta Psi(mt) relative to compound 3. In addition, DNA flow cytometric analysis shows that hybrids actively induce a marked loss of cells from the G2/M phase of the cell cycle, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Thus, we suggest that the hybrid agents are potent inducers of cell apoptosis in A2058 cells.

  DOI：

  10.1021/jm050956q

文献信息

• Novel pyrrolo[2,1-c][1,4] benzodiazepine-indole derivatives, their preparation process, and uses of the same
  申请人：Kaohsiung Medical University

  公开号：US20040054168A1

  公开（公告）日：2004-03-18

  Disclosed herein are novel pyrrolo[2,1-c][1,4]benzodiazepine-indole derivatives of formula (I): 1 wherein each of the substituents is given the definition as set forth in the Specification and claims. Also disclosed are the preparation process of these derivatives and their uses in the manufacture of pharmaceutical compositions.

  本文披露了一种新颖的嘧啶并[2,1-c][1,4]苯二氮杂环己烯-吲哚衍生物，化学式（I）如下：其中每个取代基的定义如规范和索赔中所述。还披露了这些衍生物的制备过程以及它们在制造药物组合物中的用途。
• Design, Synthesis, and Biological Evaluation of Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepine and Indole Conjugates as Anticancer Agents
  作者：Jeh-Jeng Wang、Yu-Kai Shen、Wan-Ping Hu、Ming-Chu Hsieh、Fu-Lung Lin、Ming-Kuan Hsu、Mei-Hui Hsu

  DOI：10.1021/jm050956q

  日期：2006.2.1

  A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) hybrids linked with indole carboxylates is described. These compounds were prepared by linking C-8 of 3 (DC-81) with an indole 2-carbonyl moiety (9) through carbon chain linkers to afford PBD hybrid agents 17-21 in good yields. Preliminary in vivo tests show that these hybrid agents have potent antitumor activity. The cytotoxic studies of the hybrid agents on human melanoma A2058 cells indicate most of the hybrids induced higher cytotoxicity, better DNA-binding ability, an increase in the apoptotic sub-G1 population, and a significant reduction in Delta Psi(mt) relative to compound 3. In addition, DNA flow cytometric analysis shows that hybrids actively induce a marked loss of cells from the G2/M phase of the cell cycle, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Thus, we suggest that the hybrid agents are potent inducers of cell apoptosis in A2058 cells.