| 1516902-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• CAS: 1516902-65-0
• 化学式: C₁₇H₁₁BrO₅
• 分子量: 375.175
• InChiKey: YGYCNUZMEICXSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.83
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  76.74
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-methyl-2-(1-methyl-1H-indol-3-yl)ethan-1-amine 、 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3%的产率得到6-(4-bromobenzyloxy)-4-oxo-4H-chromene-2-carboxylic acid [2-(methyl-1H-indol-3-yl)-ethyl]methylamide
  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