7-bromo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide | 113081-32-6

• 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-bromo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide
• 英文别名: 8-bromo-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol;hydrobromide
• CAS: 113081-32-6
• 化学式: BrH*C₁₆H₁₆BrNO
• 分子量: 399.125
• InChiKey: IONYJCBNCWTVMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  32.3
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-bromo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide 、 3-溴丙烯 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 3-allyl-7-bromo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  (.+-.)-3-Allyl-7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines as selective high affinity D1 dopamine receptor antagonists: synthesis and structure-activity relationship

  摘要：

  Substituted 1-phenyl-3-benzazepines form a class of compounds possessing potent and selective affinity for the D1 DA receptor. 7,8-Dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 38393) and its 6-halo analogues are potent and selective D1 receptor agonists. Recently, the 3-allyl derivatives of SKF 38393 and its analogues were described as selective D1 agonists with higher D1 efficacy and CNS potency. In order to extend these results to compounds in the 7-halo-8-hydroxy-substituted antagonist series, we have synthesized and pharmacologically characterized 3-allyl analogues of 7-substituted (Cl, Br, H) 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. These 3-allyl derivatives were compared with their 3-methyl and 3-unsubstituted analogues in terms of their D1 receptor affinity and selectivity. The results have been used to generate structure-affinity relationships. The D1 receptor affinity, for 3-substitution, is found to be in the order: methyl > allyl > H. For 7-substitution, the affinity is in the order: Cl = Br > H. The 3-allyl compounds show affinity close to that of the parent (3-methyl) compounds while exhibiting a slightly diminished D1 selectivity. However, the greater lipophilicity of the 3-allyl compounds may enable them to cross the blood-brain barrier more readily and thereby exhibit higher in vivo CNS potency. Thus 3-allylbenzazepines have potential as high affinity selective Dl antagonists.

  DOI：

  10.1021/jm00079a008
• 作为产物：
  描述：

  (+/-)-7-bromo-8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine 在 三溴化硼 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 以60%的产率得到7-bromo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide
  参考文献：
  名称：

  (.+-.)-3-Allyl-7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines as selective high affinity D1 dopamine receptor antagonists: synthesis and structure-activity relationship

  摘要：

  Substituted 1-phenyl-3-benzazepines form a class of compounds possessing potent and selective affinity for the D1 DA receptor. 7,8-Dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 38393) and its 6-halo analogues are potent and selective D1 receptor agonists. Recently, the 3-allyl derivatives of SKF 38393 and its analogues were described as selective D1 agonists with higher D1 efficacy and CNS potency. In order to extend these results to compounds in the 7-halo-8-hydroxy-substituted antagonist series, we have synthesized and pharmacologically characterized 3-allyl analogues of 7-substituted (Cl, Br, H) 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. These 3-allyl derivatives were compared with their 3-methyl and 3-unsubstituted analogues in terms of their D1 receptor affinity and selectivity. The results have been used to generate structure-affinity relationships. The D1 receptor affinity, for 3-substitution, is found to be in the order: methyl > allyl > H. For 7-substitution, the affinity is in the order: Cl = Br > H. The 3-allyl compounds show affinity close to that of the parent (3-methyl) compounds while exhibiting a slightly diminished D1 selectivity. However, the greater lipophilicity of the 3-allyl compounds may enable them to cross the blood-brain barrier more readily and thereby exhibit higher in vivo CNS potency. Thus 3-allylbenzazepines have potential as high affinity selective Dl antagonists.

  DOI：

  10.1021/jm00079a008

文献信息

• 1-Phenyl-3-benzazepine compounds and medicaments containing these compounds for treating gastrointestinal motility disorders
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0244088A2

  公开（公告）日：1987-11-04

  Compounds of the formula (I) and pharmaceutically acceptable acid addition salts thereof for use in treating gastrointestinal motility disorders are described wherein R¹ is hydrogen. C₁-C₆alkyl or C₃-C₅alkenyl; R² is hydrogen, hydroxy, C₁-C₆alkoxy, halogen, trifluoromethyl, C₁-C₆alkyl, SOn(C₁-C₆)alkyl, SOnCF₃, SOnphenyl or SO₂NR⁵R⁶; R³ is hydrogen, halogen, CF₃, C₁-C₆alkyl or R⁷O; R⁴ is hydroxy, C₁-C₆alkoxy, C₁-C₆alkyl, SOn(C₁-C₆) alkyl, NH₂, NO₂, halogen, trifluoromethyl, C₁-C₆alkylsulfonamido, C₁-C₆alkanoylamino, hydroxymethyl or C₁-C₆alkoxymethyl, except that when R³ is hydroxy in the 7-position and R¹ is hydrogen or when R³ is hydroxy in the 8-position and R¹ is methyl, R⁴ may be halogen or trifluoromethyl only if it is in the 6- or 9-position; n is 0, l or 2; R⁵ and R⁶ are hydrogen or C₁-C₆alkyl; and R⁷ is hydrogen, C₁-C₆alkyl or C₁-C₆alkanoyl. Pharmaceutical compositions containing them and their use in the manufacture of medicaments for treating gastrointestinal motility disorders are described.

  式 (I) 的化合物 及其药学上可接受的用于治疗胃肠道运动紊乱的酸加成盐，其中 R¹ 是氢。C₁-C₆烷基或C₃-C₅烯基；R²是氢、羟基、C₁-C₆烷氧基、卤素、三氟甲基、C₁-C₆烷基、SOn(C₁-C₆)烷基、SOnCF₃、SOnphenyl或SO₂NR⁵R⁶；R³ 是氢、卤素、CF₃、C₁-C₆烷基或 R⁷O；R⁴ 是羟基、C₁-C₆ 烷氧基、C₁-C₆ 烷基、SOn(C₁-C₆) 烷基、NH₂、NO₂、卤素、三氟甲基、C₁-C₆ 烷基磺酰胺基、C₁-C₆ 烷酰氨基、羟甲基或 C₁-C₆ 烷氧基甲基、但当 R³ 在 7 位为羟基而 R¹ 为氢，或当 R³ 在 8 位为羟基而 R¹ 为甲基时，R⁴ 只有在 6 或 9 位时才可以是卤素或三氟甲基；n为0、l或2；R⁵和R⁶为氢或C₁-C₆烷基；以及R⁷为氢、C₁-C₆烷基或C₁-C₆烷酰基。 描述了含有它们的药物组合物及其在制造治疗胃肠道运动紊乱药物中的用途。
• (.+-.)-3-Allyl-7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines as selective high affinity D1 dopamine receptor antagonists: synthesis and structure-activity relationship
  作者：Nandkishore Baindur、Mai Tran、Hyman B. Niznik、H. C. Guan、Phillip Seeman、John L. Neumeyer

  DOI：10.1021/jm00079a008

  日期：1992.1

  Substituted 1-phenyl-3-benzazepines form a class of compounds possessing potent and selective affinity for the D1 DA receptor. 7,8-Dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 38393) and its 6-halo analogues are potent and selective D1 receptor agonists. Recently, the 3-allyl derivatives of SKF 38393 and its analogues were described as selective D1 agonists with higher D1 efficacy and CNS potency. In order to extend these results to compounds in the 7-halo-8-hydroxy-substituted antagonist series, we have synthesized and pharmacologically characterized 3-allyl analogues of 7-substituted (Cl, Br, H) 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. These 3-allyl derivatives were compared with their 3-methyl and 3-unsubstituted analogues in terms of their D1 receptor affinity and selectivity. The results have been used to generate structure-affinity relationships. The D1 receptor affinity, for 3-substitution, is found to be in the order: methyl > allyl > H. For 7-substitution, the affinity is in the order: Cl = Br > H. The 3-allyl compounds show affinity close to that of the parent (3-methyl) compounds while exhibiting a slightly diminished D1 selectivity. However, the greater lipophilicity of the 3-allyl compounds may enable them to cross the blood-brain barrier more readily and thereby exhibit higher in vivo CNS potency. Thus 3-allylbenzazepines have potential as high affinity selective Dl antagonists.