N-<2-hydroxy-2-(3-methoxyphenyl)ethyl>-2-(2-chloro-3,4-dimethoxyphenyl)ethylamine | 67287-60-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-<2-hydroxy-2-(3-methoxyphenyl)ethyl>-2-(2-chloro-3,4-dimethoxyphenyl)ethylamine
• 英文别名: N-[2-(2-chloro-3,4-dimethoxyphenyl)-ethyl]-2-hydroxy-2-(m-methoxyphenyl)ethylamine；2-[2-(2-Chloro-3,4-dimethoxyphenyl)ethylamino]-1-(3-methoxyphenyl)ethanol
• CAS: 67287-60-9
• 化学式: C₁₉H₂₄ClNO₄
• 分子量: 365.857
• InChiKey: IMBVEEUXEAFDFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  60
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-<2-hydroxy-2-(3-methoxyphenyl)ethyl>-2-(2-chloro-3,4-dimethoxyphenyl)ethylamine 在 氢溴酸 作用下， 反应 3.0h， 以66%的产率得到6-chloro-7,8-dihydroxy-1-(m-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide
  参考文献：
  名称：

  取代的6-氯-1-苯基-2,3,4,5-四氢-1H-3-苯并ze庚因的多巴胺能活性。

  摘要：

  合成了6-氯-7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并ze庚因并将其评估为中枢和周围多巴胺受体的激动剂。这些苯并ze庚因是通过将某些氨基醇环化，然后将前体的7,8-二甲氧基基团脱甲基为7,8-儿茶酚部分而制备的。通过测量对肾血流量的影响并计算伴随的肾血管阻力变化，确定了麻醉狗的多巴胺能活性的初步证据。最有效的化合物在1-苯基上含有羟基或在3'位置被氯，甲基或三氟甲基取代。中心多巴胺能活性的证据是通过测量黑质病变的大鼠的旋转效应以及体外测定大鼠纹状体腺苷酸环化酶的刺激而获得的。具有最佳中枢多巴胺能活性的化合物通常是亲脂性最高的苯并ze庚因，它们被取代在1-苯基的3'位置，并含有3-N-甲基或3-N-烯丙基。

  DOI：

  10.1021/jm00346a005
• 作为产物：
  描述：

  3-甲氧基苯甲醛 在 sodium hydride 、 二甲基亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 N-<2-hydroxy-2-(3-methoxyphenyl)ethyl>-2-(2-chloro-3,4-dimethoxyphenyl)ethylamine
  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

文献信息

• Method for 6-bromination of 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
  申请人：SmithKline Corporation

  公开号：US04160765A1

  公开（公告）日：1979-07-10

  The preparation of 6-bromo-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines is described by direct bromination of the nucleus.

  6-溴-7,8-二甲氧基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂环庚三烯的制备是通过直接核溴化描述的。
• 6-Halo-7,8-d
  申请人：SmithKline Corporation

  公开号：US04197297A1

  公开（公告）日：1980-04-08

  6-Halo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines whose structures have a hydroxy group substituted on the 1-phenyl ring have potent and specific antihypertensive activity by means of their peripheral dopaminergic effect. The lead compound of the series is 6-chloro-7,8-dihydroxy-(p-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepi ne methane sulfonate.

  结构上在1-苯基环上有一个羟基取代的6-卤-7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并环辛烷类化合物具有强效和特异的降压活性，通过其外周多巴胺能作用实现。该系列的首要化合物是6-氯-7,8-二羟基-(对羟基苯基)-2,3,4,5-四氢-1H-3-苯并环辛烷甲磺酸盐。
• 6-Halo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines
  申请人：SmithKline Corporation

  公开号：US04255422A1

  公开（公告）日：1981-03-10

  7,8-Dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines having a halo substituent at the 6-position have potent dopaminergic activity. The 6-chloro congeners are most active.

  在6位有卤素取代基的7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并吡啶具有强大的多巴胺活性。其中，6-氯同系物活性最强。
• Synergistic antihypertensive compositions
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0022330A2

  公开（公告）日：1981-01-14

  Compositions useful for treating hypertension contain a renal dopaminergic agent, for example a 6,9-optionally substituted-7,8-dihydroxy-1-pydroxyphenyl)- 2,3,4,5-tetrahydro-1H-3-benzazepine or a salt and or O-alkanoyl ester thereof, combined with a diuretic agent. Especially useful are compositions containing as active ingredients 6-chloro-7,8-dihydroxy- 1-(4-hydroxyphenyl)- 2,3,4,5-tetrahydro-1H- 3-benzazepine or a pharmaceutically acceptable salt thereof combined with triamterene, hydro chlorothiazide or ticrynafen. The medicinal compositions are administered internally but most readily orally.

  用于治疗高血压的组合物含有肾多巴胺能剂，例如 6，9-可选取代的-7，8-二羟基-1-(4-羟基苯基)-2，3，4，5-四氢-1H-3-苯并氮杂卓或其盐和或 O-烷酰酯，并与利尿剂结合使用。特别有用的是含有 6-氯-7,8-二羟基-1-(4-羟基苯基)-2,3,4,5-四氢-1H-3-苯并氮杂卓或其药学上可接受的盐作为有效成分的复方制剂与三苯氧胺、氢氯噻嗪或替曲奈芬的复方制剂。这些药物组合物可内服，但最常用的是口服。
• PFEIFFER, F. R.;WILSON, J. W.;WEINSTOCK, J.;KUO, G. Y.;CHAMBERS, P. A.;HO+, J. MED. CHEM., 1982, 25, N 4, 352-358
  作者：PFEIFFER, F. R.、WILSON, J. W.、WEINSTOCK, J.、KUO, G. Y.、CHAMBERS, P. A.、HO+

  DOI：——

  日期：——