(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol | 654653-81-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol
• CAS: 654653-81-3
• 化学式: C₂₈H₂₈BrFN₂O₂
• 分子量: 523.445
• InChiKey: TZNZMTAIOJDNJP-IXCJQBJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  45.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  zinc(II) cyanide 、 (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三(邻甲基苯基)磷 、 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以62%的产率得到
  参考文献：
  名称：

  6-Cyano Analogues of Bedaquiline as Less Lipophilic and Potentially Safer Diarylquinolines for Tuberculosis

  摘要：

  Bedaquiline (1) is a new drug for tuberculosis and the first of the diarylquinoline class. It demonstrates excellent efficacy against TB but induces phospholipidosis at high doses, has a long terminal elimination half-life (due to its high lipophilicity), and exhibits potent hERG channel inhibition, resulting in clinical QTc interval prolongation. A number of structural ring A analogues of bedaquiline have been prepared and evaluated for their anti-M.tb activity (MIC90), with a view to their possible application as less lipophilic second generation compounds. It was previously observed that a range of 6 -substituted analogues of 1 demonstrated a positive correlation between potency (MIC90) toward M.tb and drug lipophilicity. Contrary to this trend, we discovered, by virtue of a clogP/M.tb score, that a 6-cyano (CN) substituent provides a substantial reduction in lipophilicity with only modest effects on MIC values, suggesting this substituent as a useful tool in the search for effective and safer analogues of 1.

  DOI：

  10.1021/acsmedchemlett.7b00196
• 作为产物：
  描述：

  3'-氟苯乙酮 在 盐酸 、 正丁基锂 作用下， 以 四氢呋喃 、 乙醇 、 环己烷 、 水 为溶剂， 反应 5.5h， 生成 (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol 、 (1R,2R)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol
  参考文献：
  名称：

  6-Cyano Analogues of Bedaquiline as Less Lipophilic and Potentially Safer Diarylquinolines for Tuberculosis

  摘要：

  Bedaquiline (1) is a new drug for tuberculosis and the first of the diarylquinoline class. It demonstrates excellent efficacy against TB but induces phospholipidosis at high doses, has a long terminal elimination half-life (due to its high lipophilicity), and exhibits potent hERG channel inhibition, resulting in clinical QTc interval prolongation. A number of structural ring A analogues of bedaquiline have been prepared and evaluated for their anti-M.tb activity (MIC90), with a view to their possible application as less lipophilic second generation compounds. It was previously observed that a range of 6 -substituted analogues of 1 demonstrated a positive correlation between potency (MIC90) toward M.tb and drug lipophilicity. Contrary to this trend, we discovered, by virtue of a clogP/M.tb score, that a 6-cyano (CN) substituent provides a substantial reduction in lipophilicity with only modest effects on MIC values, suggesting this substituent as a useful tool in the search for effective and safer analogues of 1.

  DOI：

  10.1021/acsmedchemlett.7b00196