7-Chloro-1,3,4,5-tetrahydro-3-hydroxy-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one | 107967-01-1

• 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: 7-Chloro-1,3,4,5-tetrahydro-3-hydroxy-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one
• 英文别名: methyl 7-chloro-3-hydroxy-4-(4-methoxyphenyl)-2-oxo-4,5-dihydro-1H-1-benzazepine-3-carboxylate
• CAS: 107967-01-1
• 化学式: C₁₉H₁₈ClNO₅
• 分子量: 375.809
• InChiKey: FJPQFGCUWZOIRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-Chloro-1,3,4,5-tetrahydro-3-hydroxy-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one 生成 cis-1,3,4,5-tetrahydro-7-chloro-3-hydroxy-4-(4-methoxyphenyl)-2H-1-benzazepin-2-one
  参考文献：
  名称：

  FLOYD, DAVID;KRAPCHO, JOHN

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氯-2-硝基甲苯 在 盐酸 、 氧气 、 sodium methylate 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 tin(ll) chloride 、 三甲氧基磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 7-Chloro-1,3,4,5-tetrahydro-3-hydroxy-3-(methoxycarbonyl)-4-(4-methoxyphenyl)-2H-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

文献信息

• Benzazepine derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04748239A1

  公开（公告）日：1988-05-31

  Vasodilating activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof.

  扩血管活性由具有以下结构式的化合物和其药用可接受的盐所表现。
• 3-substituted benzazepines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04767756A1

  公开（公告）日：1988-08-30

  Benzazepine derivatives useful, for example, as cardiovascular agents, are disclosed. These compounds have the general formula ##STR1## and pharmaceutically acceptable salts thereof.

  本发明揭示了苯并噻唑衍生物，例如作为心血管药物有用。这些化合物具有一般式##STR1##和其药学上可接受的盐。
• FLOYD, DAVID;KRAPCHO, JOHN
  作者：FLOYD, DAVID、KRAPCHO, JOHN

  DOI：——

  日期：——
• US4767756A
  申请人：——

  公开号：US4767756A

  公开（公告）日：1988-08-30
• US4748239A
  申请人：——

  公开号：US4748239A

  公开（公告）日：1988-05-31