6-bromo-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine | 67287-41-6

• 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: 6-bromo-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine
• 英文别名: 6-bromo-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine；6-Brom-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin；9-bromo-7,8-dimethoxy-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
• CAS: 67287-41-6
• 化学式: C₁₈H₂₀BrNO₂
• 分子量: 362.266
• InChiKey: WUISFYZOKPXMQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromo-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine 在 正丁基锂 作用下， 以 乙醚 、 甲苯 为溶剂， 生成 6-carboxy-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride
  参考文献：
  名称：

  6-Carboxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine compounds and use

  摘要：

  一组1-苯基-3-苯并噁唑啉类化合物，其结构特征是在6位具有一个羧基取代基，这些化合物是多巴胺能药物或用于制备其他多巴胺能药物的中间体。具体说明的物种包括6-羧甲氧基-7,8-二羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并噁唑啉、6-羧基-7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并噁唑啉和6-羧甲氧基-7,8-二羟基-1-(4'-羟基苯基)-2,3,4,5-四氢-1H-3-苯并噁唑啉。

  公开号：

  US04165372A1
• 作为产物：
  描述：

  7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine 在 溴 、 乙酸酐 作用下， 以63%的产率得到6-bromo-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine
  参考文献：
  名称：

  Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D1 receptor activities

  摘要：

  A series of racemic 6-aryl substituted 1-phenylbenzazepines 7a-e, and 17a,b were prepared. All these compounds showed binding potencies compatible to or much higher than that of the prototypic (+/-)-SKF- 38393 ((+/-)-1) and (+/-)-SKF-83959 (3) for the D(1) receptor. Among analogs of (+/-)-SKF-38393, compounds 7b, 7c and 7e possess 10-, 2- and 7-fold enhancement in binding for the D(1) receptor, respectively. Lower but compatible potency to that of (+/-)-1 was observed for compounds 7a and 7d. The optimal 6-substituents (m-tolyl, and 2 '-naphthyl) were applied to the skeleton of (+/-)-SKF-83959 (3). The resulting compounds 17a, b displayed high affinity at the D(1) receptor, only slightly lower than that of (3). These two compounds also showed good binding at the D(2) receptor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.049

文献信息

• Synthesis and renal vasodilator activity of some dopamine agonist 1-aryl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diols: halogen and methyl analogs of fenoldopam
  作者：Joseph Weinstock、David L. Ladd、James W. Wilson、Charles K. Brush、Nelson C. F. Yim、Gregory Gallagher、Mary E. McCarthy、Joanne Silvestri、Henry M. Sarau

  DOI：10.1021/jm00161a029

  日期：1986.11

  Certain 6-halo-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines were found to be potent D-1 dopamine agonists. The 1-(4-hydroxyphenyl) analogues did not have central nervous system activity because their high polarity inhibited entry into the brain. However, these compounds were potent renal vasodilators. Fenoldopam, the 6-chloro analogue, is an especially significant member of the series, and its synthesis

  发现某些6-卤代-1-苯基-2,3,4,5-四氢-1H-3-苯并ze庚因是有效的D-1多巴胺激动剂。1-（4-羟苯基）类似物不具有中枢神经系统活性，因为它们的高极性抑制了其进入大脑。但是，这些化合物是有效的肾血管扩张药。非氯多巴，6-氯类似物，是该系列中特别重要的成员，其合成，药理和临床特性已得到广泛研究。6-甲基和6-碘同系物是有效的肾血管扩张剂，但通过刺激大鼠尾状腺苷酸环化酶测定，非有效的部分D-1激动剂。可能的合理化建议这些活动具有不同的受体储备。9位取代的苯并庚因多巴胺激动剂不活跃或效力低下，
• 6-Carboxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine compounds and use
  申请人：SmithKline Corporation

  公开号：US04165372A1

  公开（公告）日：1979-08-21

  A group of 1-phenyl-3-benzazepines with structures characterized by having a carboxy derived substituent at position 6 which are dopaminergic agents or are intermediates for preparing other dopaminergic agents. Particular illustrative species include 6-carbomethoxy-7,8-dihydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-ben zazepine, 6-carboxy-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine and 6-carbomethoxy-7,8-dihydroxy-1-(4'-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3- benzazepine.

  一组1-苯基-3-苯并噁唑啉类化合物，其结构特征是在6位具有一个羧基取代基，这些化合物是多巴胺能药物或用于制备其他多巴胺能药物的中间体。具体说明的物种包括6-羧甲氧基-7,8-二羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并噁唑啉、6-羧基-7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并噁唑啉和6-羧甲氧基-7,8-二羟基-1-(4'-羟基苯基)-2,3,4,5-四氢-1H-3-苯并噁唑啉。
• Pharmacologically active 6-lower alkyl-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines, method of preparing them and intermediates
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0002327A1

  公开（公告）日：1979-06-13

  6-Lower alkyl-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-IH-3-benzazepines of formula: in which: R is a lower alkyl of 1-6 carbons; R, is hydrogen, benzyl, phenethyl, lower alkanoyl of 1-5 carbons, lower alkyl of 1-5 carbons, lower alkyenyl of 3-5 carbons, furyl methyl, thienylmethyl or phenacyl; R2 and R3 are each hydrogen, lower alkyl of 1-5 carbons, lower alkanoyl of 2-5 carbons, benzyl or, when taken together, methylene; and R4 is hydrogen or one or two substituents from the group comprising trifluoromethyl, halo, methyl, methoxy, acetoxy, hydroxy or methylthio; or pharmaceutically acceptable, acid addition salts thereof show dopaminergic activity. Intermediates and chemical methods for preparing them are described. An important species is 6-methyl-7,8-dihydroxy-l(p-hydroxyphenyl) -2,3,4,5- tetrahydro -1N-3- benzazepine, as the base or one of its salts, which has antihypertensive activity.

  式中的 6-低级烷基-7,8-二羟基-1-苯基-2,3,4,5-四氢-IH-3-苯并氮杂卓： 其中 R是1-6个碳原子的低级烷基； R，是氢、苄基、苯乙基、1-5 个碳原子的低级烷酰基、1-5 个碳原子的低级烷基、3-5 个碳原子的低级烯基、呋喃甲基、噻吩甲基或苯乙基； R2 和 R3 分别是氢、1-5 个碳原子的低级烷基、2-5 个碳原子的低级烷酰基、苄基或合起来是亚甲基；以及 R4 是氢或来自三氟甲基、卤代、甲基、甲氧基、乙酰氧基、羟基或甲硫基等组的一个或两个取代基；或其药学上可接受的酸加成盐 显示多巴胺能活性。 本文介绍了中间体和制备它们的化学方法。其中一种重要的中间体是 6-甲基-7,8-二羟基-l（对羟基苯基）-2,3,4,5-四氢-1N-3-苯并氮杂卓，它的碱或盐具有抗高血压活性。
• 7,8-Substituted-1-phenyl-2,3,4,5-tetrahydro-1-H-3-benzazepines
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0026505A1

  公开（公告）日：1981-04-08

  A new series of 7,8-disubstituted-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines of use as intermediates in preparing compounds having dopaminergic activity which are described and claimed in European Patent Application 78300633.1.

  欧洲专利申请 78300633.1 中描述并声称了一系列新的 7,8-二取代-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓，可用作制备具有多巴胺能活性的化合物的中间体。
• Substituted benzazepines, processes for preparing them and pharmaceutical compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0004794B1

  公开（公告）日：1982-04-28