2-[(3S,4S)-4-(4-Methoxy-phenyl)-3-methyl-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl]-propionitrile | 128510-18-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-[(3S,4S)-4-(4-Methoxy-phenyl)-3-methyl-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl]-propionitrile
• CAS: 128510-18-9
• 化学式: C₂₂H₂₁F₃N₂O₂
• 分子量: 402.416
• InChiKey: OEEUPDCPLOLMEB-HUUYTVAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.94
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  53.33
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-[(3S,4S)-4-(4-Methoxy-phenyl)-3-methyl-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl]-propionitrile 在 Rh/Al₂O₃ 、 氨 、 氢气 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以0.56 g的产率得到(3S,4S)-1-(1-aminopropan-2-yl)-4-(4-methoxyphenyl)-3-methyl-6-(trifluoromethyl)-4,5-dihydro-3H-1-benzazepin-2-one
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site

  摘要：

  We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presence of two pharmacophores: a 4'-aryl methyl ether and a basic substituent appended to N1 with a pK(a) in the physiological range. When these constraints are satisfied, a wide variety of substitution is tolerated at C6, C7, and C3. The presence of an electron-withdrawing group at C6 appears to enhance potency in vitro and in vivo. For such benzazepinones, activity is primarily dependent upon lipophilicity, as measured by log P. We believe these compounds must partition into the cell membrane in order to access their receptor. The quaternary methiodide 15k was used to demonstrate that the binding site for benzazepinones is on the intracellular face of the membrane. This work represents the first comprehensive SAR of diltiazem-like calcium channel blockers.

  DOI：

  10.1021/jm00082a020
• 作为产物：
  描述：

  dimethyl <1-(4-methoxyphenyl)-2-<2-nitro-6-(trifluoromethyl)phenyl>ethyl>propanedioate 在 palladium on activated charcoal 氢气 、 sodium methylate 、 sodium hydride 、 lithium bromide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 45.0 ℃ 、275.79 kPa 条件下， 反应 17.42h， 生成 2-[(3S,4S)-4-(4-Methoxy-phenyl)-3-methyl-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl]-propionitrile
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site

  摘要：

  We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presence of two pharmacophores: a 4'-aryl methyl ether and a basic substituent appended to N1 with a pK(a) in the physiological range. When these constraints are satisfied, a wide variety of substitution is tolerated at C6, C7, and C3. The presence of an electron-withdrawing group at C6 appears to enhance potency in vitro and in vivo. For such benzazepinones, activity is primarily dependent upon lipophilicity, as measured by log P. We believe these compounds must partition into the cell membrane in order to access their receptor. The quaternary methiodide 15k was used to demonstrate that the binding site for benzazepinones is on the intracellular face of the membrane. This work represents the first comprehensive SAR of diltiazem-like calcium channel blockers.

  DOI：

  10.1021/jm00082a020