6-Chloro-3-cyclopropylmethyl-7,8-dimethoxy-1-(4-methoxy-phenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine | 81941-90-4

• 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-3-cyclopropylmethyl-7,8-dimethoxy-1-(4-methoxy-phenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine
• 英文别名: 9-chloro-3-(cyclopropylmethyl)-7,8-dimethoxy-5-(4-methoxyphenyl)-1,2,4,5-tetrahydro-3-benzazepine
• CAS: 81941-90-4
• 化学式: C₂₃H₂₈ClNO₃
• 分子量: 401.933
• InChiKey: PSUBVQNEDVXGEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 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：

  6-Chloro-3-cyclopropylmethyl-7,8-dimethoxy-1-(4-methoxy-phenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 6-chloro-3-(cyclopropylmethyl)-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 在 硼烷 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 19.0h， 生成 6-Chloro-3-cyclopropylmethyl-7,8-dimethoxy-1-(4-methoxy-phenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine
  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

• New dopaminergic benzazepines
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0044709A1

  公开（公告）日：1982-01-27

  A new series of compounds having renal vasodilating activity is described. The compounds are 3-cycloalkylmethyl-7,8-dihydroxy-6-halo-1-(p-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepines, tri-O-lower alkanoyl esters thereof and/or pharmaceutically acceptable acid addition salts thereof. They can be prepared by deetherification of the corresponding tri-lower alkyl ethers thereof.

  本文描述了一系列具有肾血管扩张活性的新化合物。这些化合物是 3-环烷基甲基-7,8-二羟基-6-卤-1-（对羟基苯基）-2,3,4,5-四氢-1H-3-苯并氮杂卓、其三-O-低级烷酰基酯和/或其药学上可接受的酸加成盐。它们可以通过相应的三低烷基醚的脱醚反应制备。
• BRENNEERR, L. M.
  作者：BRENNEERR, L. M.

  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：——
• US4328153A
  申请人：——

  公开号：US4328153A

  公开（公告）日：1982-05-04
• 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.