(±)-1-苯基-2,3,4,5-四氢-(1H)-3-苯并ze庚因-7,8-二醇氢溴酸盐 | 20012-10-6

• 物质功能分类: 医药中间体 - 杂环化合物
• 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: (±)-1-苯基-2,3,4,5-四氢-(1H)-3-苯并ze庚因-7,8-二醇氢溴酸盐
• 英文名称: 7,8-Dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine Hydrobromide
• 英文别名: SKF 38393 hydrobromide；(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide；(+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide；(±)-SKF 38393 hydrobromide；SKF-38393 hydrobromide；5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol;hydrobromide
• CAS: 20012-10-6
• 化学式: BrH*C₁₆H₁₇NO₂
• 分子量: 336.228
• InChiKey: INNWVRBZMBCEJI-UHFFFAOYSA-N

物化性质

• 熔点：
  283-285 °C
• 溶解度：
  在温和加热的情况下在水中溶解至 25 mM，在温和加热的情况下在乙醇中溶解至 25 mM

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 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：
  52.5
• 氢给体数：
  4
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，置于干燥处

制备方法与用途

SKF 38393 碘溴盐是一种对多巴胺 D1 受体的选择性激动剂，其 IC50 值为 110 nM。

反应信息

• 作为反应物：
  描述：

  (±)-1-苯基-2,3,4,5-四氢-(1H)-3-苯并ze庚因-7,8-二醇氢溴酸盐 在 硼烷四氢呋喃络合物 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (R,S)-7,8-dihydroxy-1H-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  （+/-）-3-烯丙基-6-溴-7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并ze庚因，一种新的高亲和力D1多巴胺受体配体：合成与构效关系。

  摘要：

  7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并ze庚因形成一系列对D1多巴胺受体具有高亲和力的化合物。先前已证明6-氯衍生物具有增强的亲和力，选择性和激动剂活性。为了研究取代6-氯取代6-溴的效果，我们合成了一系列化合物并评估了它们对D1受体的亲和力。结果表明6-溴衍生物与6-氯衍生物具有几乎相同的亲和力，这一发现与D1拮抗剂7-卤代-8-羟基-1-苯基-2,3,4,5-相似。四氢-1H-3-苯并ze庚因系列。从目前的工作来看，3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4，

  DOI：

  10.1021/jm00116a004
• 作为产物：
  描述：

  N-[2-(3,4-二甲氧基苯基)乙基]-2-苯基-2-羟基乙胺 在 氢溴酸 作用下， 反应 3.0h， 以90%的产率得到(±)-1-苯基-2,3,4,5-四氢-(1H)-3-苯并ze庚因-7,8-二醇氢溴酸盐
  参考文献：
  名称：

  Dopamine agonists related to 3-allyl-6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol, 6-position modifications

  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-diol (SK&F 82526) retains the DA-1 agonist potency of the latter compound but unlike the parent also shows substantial DA-2 agonist activity. In a previous study of N-substituted benzazepines these combined agonist effects were shown to be uniquely associated with the N-allyl group. A continuation of this research has examined dependency of combined DA-2/DA-1 agonist activities on 6-position modification with the specific objective of developing an agonist with maximum effectiveness and potency at the DA-2 receptor subtype. DA-2 agonist activity was measured in a rabbit ear artery assay, and DA-1 agonist activity was determined in an adenylate cyclase assay. Replacing chloro with bromo retains the activity pattern and the potency of the chloro compound; replacement with a hydrogen causes a decrease of both DA-1 and DA-2 receptor activating potency. Introduction of a 6-methyl group causes loss of DA-2 agonist activity and reduction in DA-1 agonist potency. Substitution with a 6-fluoro provides the best balance of DA-2 and DA-1 agonist activities; this compound was moderately potent in both assays.

  DOI：

  10.1021/jm00384a006

文献信息

• 2,3,4,5-Tetrahydro-1H-3-benzazepine-7,8-diones
  申请人：SmithKline Corporation

  公开号：US04108989A1

  公开（公告）日：1978-08-22

  Novel benzazepine derivatives having central and peripheral dopaminergic activity useful in treating Parkinson's and cardiovascular diseases. The compounds have additional use as intermediates for the synthesis of other benzazepines with similar useful properties. The 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-dione derivatives are particularly useful.

  新型苯并哌啶衍生物具有中枢和外周多巴胺活性，可用于治疗帕金森病和心血管疾病。这些化合物还可用作合成具有类似有用性质的其他苯并哌啶的中间体。其中1-苯基-2,3,4,5-四氢-1H-3-苯并哌啶-7,8-二酮衍生物特别有用。
• Alkylthio-7,8-dihdroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines
  申请人：SmithKline Corporation

  公开号：US04206210A1

  公开（公告）日：1980-06-03

  A new series of lower alkylthio-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines having potent central dopaminergic activity of utility in treating Parkinson's disease. The 6-and 9-methylthio compounds are particularly of use.

  一系列新的具有治疗帕金森病中枢多巴胺活性的低烷基硫基-7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并哌啶类化合物。其中6-和9-甲硫基化合物特别有用。
• 7,8-Amino, hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines, process for their preparation and pharmaceutical compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0033632A2

  公开（公告）日：1981-08-12

  A group of 1-phenyl-2,3,4,5-tetrahydro-1H-3-benz- azepines having structures with amino, hydroxy substituents at the 7,8-positions of the benzazepine nucleus is disclosed. Also described are pharmacodynamic pharmaceutical compositions containing them and processes for their preparation.

  本研究公开了一组 1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓，其结构在苯并氮杂卓核的 7、8 位上具有氨基和羟基取代基。还描述了含有它们的药效学药物组合物及其制备工艺。
• Method for post mortem diagnosis of Alzheimer's Disease (AD)
  申请人：Red Bull GmbH

  公开号：EP2806276A1

  公开（公告）日：2014-11-26

  Disclosed is a method for diagnosing Alzheimer's Disease (AD) post mortem, wherein the amount of at least one receptor complex, selected from the group consisting of nicotinic acetylcholine receptor complex 4, nicotinic acetylcholine receptor complex 7, dopamine receptor complex D1 and dopamine receptor complex D2, is measured in a brain sample of a patient and diagnosing AD, if the amount of the complex in the sample is increased compared to normal, non-AD levels.

  本发明公开了一种用于死后诊断阿尔茨海默病（AD）的方法，该方法测量患者脑样本中至少一种受体复合物的含量，这些受体复合物选自由烟碱乙酰胆碱受体复合物 4、烟碱乙酰胆碱受体复合物 7、多巴胺受体复合物 D1 和多巴胺受体复合物 D2 组成的组，如果样本中的复合物含量与正常非 AD 水平相比有所增加，则诊断为 AD。
• 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