3-allyl-6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)2,3,4,5-tetrahydro-1H-3-benzazepine | 77386-10-8

• 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: 3-allyl-6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)2,3,4,5-tetrahydro-1H-3-benzazepine
• 英文别名: 3-allyl-6-chloro-7,8-dimethoxy-1-(p-methoxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine；9-chloro-7,8-dimethoxy-5-(4-methoxyphenyl)-3-prop-2-enyl-1,2,4,5-tetrahydro-3-benzazepine
• CAS: 77386-10-8
• 化学式: C₂₂H₂₆ClNO₃
• 分子量: 387.906
• InChiKey: FFVFANRIQXCVLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-allyl-6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)2,3,4,5-tetrahydro-1H-3-benzazepine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 3-allyl-6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7.8-diol
  参考文献：
  名称：

  Dopamine receptor agonists: 3-allyl-6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol and a series of related 3-benzazepines

  摘要：

  The N-allyl derivative (SK&F 85174) of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-dio l (SK&F 82526) not only retains the exceptional D-1 agonist potency of its parent but also displays reasonably potent D-2 agonist activity, as measured by a dopamine-sensitive adenylate cyclase test and a rabbit ear artery assay, respectively. Several additional N-substituted compounds were prepared to explore the D-2/D-1 agonist relationship. The N-methyl analogue retained good D-2 agonist potency, but this substitution converted D-1 agonist activity into antagonist activity. Most other N-substituents sharply decreased D-2 agonist potency including the N-n-propyl group. This observation was surprising since the introduction of mono- or di-N-n-propyl substituent(s) is commonly linked with retention or enhancement of D-2 agonist potency in other series of dopamine agonists. The N-(2-hydroxyethyl) analogue retains about one-fourth the D-2 potency of SK&F 85174. Several synthetic methods were used to prepare these compounds. N-Allylation of a trimethoxybenzazepine followed by cleavage of the methyl ethers with boron tribromide was the preferred method. Other methods used were direct alkylation of the trihydroxy secondary amine, i.e., SK&F 82526, and an acylation-amide reduction-cleavage method.

  DOI：

  10.1021/jm00155a024
• 作为产物：
  描述：

  6-氯-2,3,4,5-四氢-7,8-二甲氧基-1-(4-甲氧基苯基)-1H-3-苯并氮杂卓 、 3-溴丙烯 在 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 生成 3-allyl-6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  7,8-Dihydroxy-1-(sulfamylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine

  摘要：

  新的7,8-二羟基-1-(磺酰基苯基)-2,3,4,5-四氢-1H-3-苯并氮平具有药物活性，同时提供了新的中间体和合成方法。领先的化合物为6-氯-7,8-二羟基-1-(对磺酰基苯基)-2,3,4,5-四氢-1H-3-苯并氮平，具有非常强的肾脏多巴胺能活性。

  公开号：

  US04285938A1

文献信息

• 7,8-Dihydroxy-1-(sulfamylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine
  申请人：SmithKline Corporation

  公开号：US04285938A1

  公开（公告）日：1981-08-25

  New 7,8-dihydroxy-1-(sulfamylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepines having pharmaceutical activity together with new intermediates and methods of synthesis for preparing them. The lead compound is 6-chloro-7,8-dihydroxy-1-(p-sulfamylphenyl)-2,3,4,5-tetrahydro-1H-3-benzaz epine which has very potent renal dopaminergic activity.

  新的7,8-二羟基-1-(磺酰基苯基)-2,3,4,5-四氢-1H-3-苯并氮平具有药物活性，同时提供了新的中间体和合成方法。领先的化合物为6-氯-7,8-二羟基-1-(对磺酰基苯基)-2,3,4,5-四氢-1H-3-苯并氮平，具有非常强的肾脏多巴胺能活性。
• 7,8-Dihydroxy-1-(sulfamylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine derivatives, a process for their preparation and compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0027348A1

  公开（公告）日：1981-04-22

  The invention provides 7,8-dihydroxy-1-(sulfonyl- phenyl)- 2,3,4,5-tetrahydro-1H-3-benzazepines having pharmaceutical activity, in particular renal dopaminergic activity as with the preferred 6-chloro-7,8- dihydroxy-1-(p-sulfamylphenyl)-2,3,4,5- tetrahydro-1H-3-benzazepine. The invention includes 0-alkanoyl derivatives thereof and pharmaceutically acceptable acid addition salts. The compounds of the invention can be prepared by reacting an appropriate 1-halosulfamylphenyl-2,3,4,5- tetrahydro-1 H-3-benzazepine, protected where necessary, with ammonia or a suitable amine.

  本发明提供的7,8-二羟基-1-(磺酰基苯基)-2,3,4,5-四氢-1H-3-苯并氮杂卓具有药物活性，特别是肾多巴胺活性，如优选的6-氯-7,8-二羟基-1-(对磺酰基苯基)-2,3,4,5-四氢-1H-3-苯并氮杂卓。本发明包括其 0-烷酰基衍生物和药学上可接受的酸加成盐。本发明的化合物可通过将适当的 1-卤磺酰胺基苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓（必要时加以保护）与氨或适当的胺反应来制备。
• WEINSTOCK, J.
  作者：WEINSTOCK, J.

  DOI：——

  日期：——
• ROSS, S. T.;FRANZ, R. G.;WILSON, J. W.;BRENNER, M.;DEMARINIS, R. M.;HIEBL+, J. MED. CHEM., 1986, 29, N 5, 733-740
  作者：ROSS, S. T.、FRANZ, R. G.、WILSON, J. W.、BRENNER, M.、DEMARINIS, R. M.、HIEBL+

  DOI：——

  日期：——
• 3-Allyl-7,8-dihydroxy-6-halo-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine derivatives, process for preparing them and compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0020107B1

  公开（公告）日：1982-08-11