8-butoxycarbonyl-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydro-isoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 8-butoxycarbonyl-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydro-isoquinoline
• 英文别名: 1,2,3,4-Tetrahydro-2-methyl-4-phenyl-8-isoquinolinecarbamic acid butyl ester；butyl N-(2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-yl)carbamate
• 化学式: C₂₁H₂₆N₂O₂
• 分子量: 338.45
• InChiKey: WUNQTSWTUXBZSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(2-nitrobenzyl)-2-(methylamino)-1-(4'-chlorophenyl)-1-ethanol 在 镍 硫酸 、 氢气 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 6.0~8.0 ℃ 、101.33 kPa 条件下， 反应 15.5h， 生成 8-butoxycarbonyl-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydro-isoquinoline
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property

  摘要：

  As shown by structure-activity relationship studies in 8-(substituted-amino)-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines, the most important structural requirement for a marked antidepressant action is the presence of an ureido, (alkoxycarbonyl)amino, or [(alkylamino)acyl]amino group attached to the isoquinoline skeleton in position 8. In one of the biological tests a significant difference was found between 8-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline (nomifensine) and the new compounds synthesized. Nearly all compounds substituted in the amino group either decrease the spontaneous motility in mice or exert no effect on it. Two syntheses have been elaborated for the preparation of the compounds represented by the general formulas II-V where R1 = hydrogen, halogen, or methyl; Y = CONHR, OCOR, or CO(CH2)nNHR, in which R = alkyl or aralkyl or NHR = cyclic amine and n = 1-2. The syntheses start either from the corresponding 8-amino-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines or from the corresponding noncyclized amino alcohols. Of the compounds, 4-(p-chlorophenyl)-8-[(ethoxy-carbonyl)amino]-2-methyl-1,2,3,4- tetrahydroisoquinoline was found to possess the highest activity.

  DOI：

  10.1021/jm00157a012

文献信息

• Isoquinoline derivatives
  申请人：EGYT Gyogyszervegyeszeti Gyar

  公开号：US04537895A1

  公开（公告）日：1985-08-27

  The invention relates to new 4-aryl-2-methyl-1,2,3,4-tetrahydro-isoquinoline derivatives of the general Formula I ##STR1## and salts thereof wherein R stands for hydrogen, lower alkyl or halogen and X represents a group of the general Formula --(CH.sub.2).sub.n --NR.sup.1 R.sup.2, --NH--R.sup.3 or --OR.sup.4, in which R.sup.1 and R.sup.2 may be the same or different and stand for hydrogen or lower alkyl or R.sup.1 and R.sup.2 together with the adjacent nitrogen atom, they are attached to, form a 5- or 6-membered saturated heterocyclic ring which may optionally contain a further oxygen or sulfur atom or an optionally lower alkyl substituted imino group; n is an integral number 1, 2, 3 or 4; R.sup.3 stands for lower alkyl or optionally substituted phenyl and R.sup.4 is lower alkyl, halogeno lower alkyl, or phenyl lower alkyl. The compounds of the general Formula I are useful as antidepressants and antiparkinsone agents. The compounds of the general Formula I can be prepared by methods known per se.

  该发明涉及一般式I的新的4-芳基-2-甲基-1,2,3,4-四氢异喹啉衍生物及其盐，其中R代表氢、较低的烷基或卤素，X代表一般式--(CH.sub.2).sub.n --NR^1 R^2、--NH--R^3或--OR^4的基团，其中R^1和R^2可以相同也可以不同，代表氢或较低的烷基，或者R^1和R^2与相邻的氮原子一起，连接形成一个可能含有进一步的氧或硫原子或一个可选择地较低烷基取代的亚胺基团的5-或6-成员饱和杂环环，n是整数1、2、3或4；R^3代表较低的烷基或可选择地取代的苯基，R^4是较低的烷基、卤代较低的烷基或苯基较低的烷基。一般式I的化合物可用作抗抑郁药和抗帕金森病药物。一般式I的化合物可以通过已知的方法制备。
• US4537895A
  申请人：——

  公开号：US4537895A

  公开（公告）日：1985-08-27
• Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property
  作者：E. Zara-Kaczian、L. Gyorgy、Gyula Deak、A. Seregi、M. Doda

  DOI：10.1021/jm00157a012

  日期：1986.7

  As shown by structure-activity relationship studies in 8-(substituted-amino)-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines, the most important structural requirement for a marked antidepressant action is the presence of an ureido, (alkoxycarbonyl)amino, or [(alkylamino)acyl]amino group attached to the isoquinoline skeleton in position 8. In one of the biological tests a significant difference was found between 8-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline (nomifensine) and the new compounds synthesized. Nearly all compounds substituted in the amino group either decrease the spontaneous motility in mice or exert no effect on it. Two syntheses have been elaborated for the preparation of the compounds represented by the general formulas II-V where R1 = hydrogen, halogen, or methyl; Y = CONHR, OCOR, or CO(CH2)nNHR, in which R = alkyl or aralkyl or NHR = cyclic amine and n = 1-2. The syntheses start either from the corresponding 8-amino-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines or from the corresponding noncyclized amino alcohols. Of the compounds, 4-(p-chlorophenyl)-8-[(ethoxy-carbonyl)amino]-2-methyl-1,2,3,4- tetrahydroisoquinoline was found to possess the highest activity.