6-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]hexyl 4-[6,7-dimethoxy-1-(phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-4-oxobutanoate | 1309235-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 6-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]hexyl 4-[6,7-dimethoxy-1-(phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-4-oxobutanoate
• CAS: 1309235-50-4
• 化学式: C₃₆H₄₁N₃O₁₁S
• 分子量: 723.801
• InChiKey: AGUQQXQLSXSNTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  51
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  178
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N-(3,4-dimethoxyphenylethyl)-2-phenoxyacetamide 在 4-二甲氨基吡啶 、 钾硼氢 、 二乙胺 、 N,N'-二环己基碳二亚胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 30.5h， 生成 6-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]hexyl 4-[6,7-dimethoxy-1-(phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-4-oxobutanoate
  参考文献：
  名称：

  Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents

  摘要：

  Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.077

文献信息

• Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents
  作者：Zhi-hong Zou、Xiao-bu Lan、Hai Qian、Wen-long Huang、Yun-man Li

  DOI：10.1016/j.bmcl.2011.07.077

  日期：2011.10

  Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects. (C) 2011 Elsevier Ltd. All rights reserved.