5-(4-bromobenzyloxy)-4-oxo-4H-chromene-2-carboxylic acid [2-(6-methoxy-1H-indol-3-yl)ethyl]amide | 1516902-69-4

• 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: 5-(4-bromobenzyloxy)-4-oxo-4H-chromene-2-carboxylic acid [2-(6-methoxy-1H-indol-3-yl)ethyl]amide
• 英文别名: 5-[(4-bromophenyl)methoxy]-N-[2-(6-methoxy-1H-indol-3-yl)ethyl]-4-oxochromene-2-carboxamide
• CAS: 1516902-69-4
• 化学式: C₂₈H₂₃BrN₂O₅
• 分子量: 547.405
• InChiKey: CDVAZDPJSYGNKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-((4-bromobenzyl)oxy)-4-oxo-4H-chromene-2-carboxylic acid 、 3-(2-氨基乙基)-6-甲氧基吲哚 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以11%的产率得到5-(4-bromobenzyloxy)-4-oxo-4H-chromene-2-carboxylic acid [2-(6-methoxy-1H-indol-3-yl)ethyl]amide
  参考文献：
  名称：

  Structure–Activity Relationships of Chromone Derivatives toward the Mechanism of Interaction with and Inhibition of Breast Cancer Resistance Protein ABCG2

  摘要：

  We recently identified a chromone derivative, 5-(4-bromobenzyloxy)-2-(2-(5-methoxyindolypethyl-1-carbonyl)-4H-chromen-4-one, named here as chromone 1, as a potent, selective, nontoxic, and nontransported inhibitor of ABCG2-mediated drug efflux (Valdameri et al. J. Med. Chem. 2012, 55, 966). We have now synthesized a series of 14 derivatives to study the structure activity relationships controlling both drug efflux and ATPase activity of ABCG2 and to elucidate their molecular mechanism of interaction and inhibition. It was found that the 4-bromobenzyloxy substituent at position 5 and the methoxyindole are important for both inhibition of mitoxantrone efflux and inhibition of basal ATPase activity. Quite interestingly, methylation of the central amide nitrogen strongly altered the high affinity for ABCG2 and the complete inhibition of mitoxantrone efflux and coupled ATPase activity. These results allowed the identification of a critical central inhibitory moiety of chromones that has never been, investigated previously in any series of inhibitors.

  DOI：

  10.1021/jm401649j

文献信息

• Structure–Activity Relationships of Chromone Derivatives toward the Mechanism of Interaction with and Inhibition of Breast Cancer Resistance Protein ABCG2
  作者：Evelyn Winter、Florine Lecerf-Schmidt、Gustavo Gozzi、Basile Peres、Mark Lightbody、Charlotte Gauthier、Csilla Ozvegy-Laczka、Gergely Szakacs、Balazs Sarkadi、Tânia B. Creczynski-Pasa、Ahcène Boumendjel、Attilio Di Pietro

  DOI：10.1021/jm401649j

  日期：2013.12.27

  We recently identified a chromone derivative, 5-(4-bromobenzyloxy)-2-(2-(5-methoxyindolypethyl-1-carbonyl)-4H-chromen-4-one, named here as chromone 1, as a potent, selective, nontoxic, and nontransported inhibitor of ABCG2-mediated drug efflux (Valdameri et al. J. Med. Chem. 2012, 55, 966). We have now synthesized a series of 14 derivatives to study the structure activity relationships controlling both drug efflux and ATPase activity of ABCG2 and to elucidate their molecular mechanism of interaction and inhibition. It was found that the 4-bromobenzyloxy substituent at position 5 and the methoxyindole are important for both inhibition of mitoxantrone efflux and inhibition of basal ATPase activity. Quite interestingly, methylation of the central amide nitrogen strongly altered the high affinity for ABCG2 and the complete inhibition of mitoxantrone efflux and coupled ATPase activity. These results allowed the identification of a critical central inhibitory moiety of chromones that has never been, investigated previously in any series of inhibitors.