6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-3-(2,3-dihydroxypropyl)-1H-3-benzazepine-7,8-diol | 100166-61-8

• 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: 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-3-(2,3-dihydroxypropyl)-1H-3-benzazepine-7,8-diol
• 英文别名: 9-Chloro-3-(2,3-dihydroxypropyl)-5-(4-hydroxyphenyl)-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol
• CAS: 100166-61-8；100166-81-2
• 化学式: C₁₉H₂₂ClNO₅
• 分子量: 379.84
• InChiKey: ZBWVZIOVYQUUOR-UHFFFAOYSA-N

物化性质

• 沸点：
  615.5±55.0 °C(Predicted)
• 密度：
  1.428±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  104
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  芬洛多潘 、 缩水甘油 以 甲醇 、 水 为溶剂， 反应 16.0h， 生成 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-3-(2,3-dihydroxypropyl)-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

文献信息

• 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
  作者：Stephen T. Ross、Robert G. Franz、James W. Wilson、Martin Brenner、Robert M. DeMarinis、J. Paul Hieble、Henry M. Sarau

  DOI：10.1021/jm00155a024

  日期：1986.5

  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.