8-氯-2,3,4,5-四氢-5-苯基-1H-3-苯并氮杂卓-7-醇氢溴酸盐 | 90955-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 8-氯-2,3,4,5-四氢-5-苯基-1H-3-苯并氮杂卓-7-醇氢溴酸盐
• 中文别名: (Z)-3-羟基-2-((苯亚氨基)-2-噻嗯基甲基)-1H-茚-1-酮
• 英文名称: 7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide
• 英文别名: 8-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol;hydron;bromide
• CAS: 90955-43-4
• 化学式: BrH*C₁₆H₁₆ClNO
• 分子量: 354.674
• InChiKey: XSWVQBLZJAURQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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

• 作为产物：
  描述：

  3-氯-4-甲氧基苯乙腈 在 硼烷 、 三溴化硼 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.5h， 生成 8-氯-2,3,4,5-四氢-5-苯基-1H-3-苯并氮杂卓-7-醇氢溴酸盐
  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

• (.+-.)-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.