N-[2-(1,3-Dihydro-isobenzofuran-5-yl)-ethyl]-N-[(R)-(+)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl]-N-methylamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: N-[2-(1,3-Dihydro-isobenzofuran-5-yl)-ethyl]-N-[(R)-(+)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl]-N-methylamine
• 英文别名: [2-(1,3-Dihydro-isobenzofuran-5-yl)-ethyl]-((R)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl)-methyl-amine；2-(1,3-dihydro-2-benzofuran-5-yl)-N-[[(1R)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl]methyl]-N-methylethanamine
• 化学式: C₂₃H₂₉NO₂
• 分子量: 351.489
• InChiKey: AEYXBENLNPAYSV-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 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：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (1,3-Dihydro-isobenzofuran-5-yl)-acetonitrile 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 23.0h， 生成 N-[2-(1,3-Dihydro-isobenzofuran-5-yl)-ethyl]-N-[(R)-(+)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl]-N-methylamine
  参考文献：
  名称：

  Structure−Activity Studies for a Novel Series of N-(Arylethyl)-N-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamines Possessing Dual 5-HT Uptake Inhibiting and α₂-Antagonistic Activities

  摘要：

  In search of an alpha(2)-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the alpha(2)-receptor (K-i = 6.71 nM) and the 5-HT uptake site (20.6 nM). A series of tertiary amine analogs of 3 were synthesized and assayed for their affinity at both the alpha(2)-receptor and the 5-HT uptake site. The structure-activity relationship reveals that a variety of structural modifications to the arylethyl fragment are possible with retention of this dual activity. On the tetralin portion, 5-OMe substitution and the (R) stereochemistry at C-l are optimal with alternate substitutions producing compounds retaining high affinity for the alpha(2)-receptor but lacking affinity for the 5-HT uptake site. Data for several rigidified 5-O-alkyl analogs suggests that the favored orientation of the oxygen lone pairs may be away from the g-position of the tetralin.

  DOI：

  10.1021/jm960723m

文献信息

• TERTIARY AND SECONDARY AMINES AS ALPHA-2 ANTAGONISTS AND SEROTONIN UPTAKE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP0646112A1

  公开（公告）日：1995-04-05
• EP0646112A4
  申请人：——

  公开号：EP0646112A4

  公开（公告）日：1997-04-02
• US5288749A
  申请人：——

  公开号：US5288749A

  公开（公告）日：1994-02-22
• [EN] TERTIARY AND SECONDARY AMINES AS ALPHA-2 ANTAGONISTS AND SEROTONIN UPTAKE INHIBITORS
  申请人：——

  公开号：WO1993012754A2

  公开（公告）日：1993-07-08

  [EN] The present invention provides an amine compound of formula (I) or a pharmaceutically acceptable salt thereof which is an antagonist for alpha-2 adrenoreceptors and which inhibits serotonin (5-hydroxytryptamine, 5-HT) uptake.
  [FR] La présente invention se rapporte à un composé d'amines de la formule (I) ou un sel pharmaceutique acceptable de celui-ci qui est un antagoniste destiné aux adrénorécepteurs alpha-2 et qui inhibe la fixation de la sérotonine (5-hydroxytryptamine, 5-HT).
• Structure−Activity Studies for a Novel Series of <i>N</i>-(Arylethyl)-<i>N</i>-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-<i>N</i>-methylamines Possessing Dual 5-HT Uptake Inhibiting and α₂-Antagonistic Activities
  作者：Michael D. Meyer、Arthur A. Hancock、Karin Tietje、Kevin B. Sippy、Rajnandan Prasad、David M. Stout、David L. Arendsen、B. Greg Donner、William A. Carroll

  DOI：10.1021/jm960723m

  日期：1997.3.1

  In search of an alpha(2)-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the alpha(2)-receptor (K-i = 6.71 nM) and the 5-HT uptake site (20.6 nM). A series of tertiary amine analogs of 3 were synthesized and assayed for their affinity at both the alpha(2)-receptor and the 5-HT uptake site. The structure-activity relationship reveals that a variety of structural modifications to the arylethyl fragment are possible with retention of this dual activity. On the tetralin portion, 5-OMe substitution and the (R) stereochemistry at C-l are optimal with alternate substitutions producing compounds retaining high affinity for the alpha(2)-receptor but lacking affinity for the 5-HT uptake site. Data for several rigidified 5-O-alkyl analogs suggests that the favored orientation of the oxygen lone pairs may be away from the g-position of the tetralin.