(1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-7-amine | 911422-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-7-amine
• 英文别名: (1S,4R,5R,7S)-4-methyl-2-(3-phenylpropyl)-5-(3-propan-2-yloxyphenyl)-2-azabicyclo[3.3.1]nonan-7-amine
• CAS: 911422-95-2
• 化学式: C₂₇H₃₈N₂O
• 分子量: 406.612
• InChiKey: BVXSRQBGQLIFPI-SLFPBUGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-7-amine 在 氢溴酸 、 溶剂黄146 作用下， 反应 15.0h， 以83%的产率得到(1S,4R,5R,7S)-(+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicylo-[3.3.1]nonan-7-amine
  参考文献：
  名称：

  Discovery of an Opioid κ Receptor Selective Pure Antagonist from a Library of N-Substituted 4β-Methyl-5-(3-hydroxyphenyl)morphans

  摘要：

  A library of compounds biased toward opioid receptor antagonist activity was prepared by incorporating N-phenylpropyl-4p-methyl-5-(3-hydroxyphenyl)morphans as the core scaffold using simultaneous solution phase synthetic methodology. From this library, N-phenylpropyl-4beta-methyl-5-(3-hydroxyphenyl)-7alpha-[3-(1-piperidinyl)propanamido]morphan [(-)-3b] was identified as the first potent and selective k opioid receptor antagonist from the 5-phenylmorphan class of opioids.

  DOI：

  10.1021/jm020084h
• 作为产物：
  描述：

  (R)-4-(3-异丙氧基苯基)-1,3-二甲基-1,2,3,6-四氢吡啶 在 4-二甲氨基吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 盐酸羟胺 、 sodium 、 三乙酰氧基硼氢化钠 、 二甲基亚砜 、 三乙胺 、 异丙醇 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 57.0h， 生成 (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-7-amine
  参考文献：
  名称：

  Discovery of an Opioid κ Receptor Selective Pure Antagonist from a Library of N-Substituted 4β-Methyl-5-(3-hydroxyphenyl)morphans

  摘要：

  A library of compounds biased toward opioid receptor antagonist activity was prepared by incorporating N-phenylpropyl-4p-methyl-5-(3-hydroxyphenyl)morphans as the core scaffold using simultaneous solution phase synthetic methodology. From this library, N-phenylpropyl-4beta-methyl-5-(3-hydroxyphenyl)-7alpha-[3-(1-piperidinyl)propanamido]morphan [(-)-3b] was identified as the first potent and selective k opioid receptor antagonist from the 5-phenylmorphan class of opioids.

  DOI：

  10.1021/jm020084h

文献信息

• Discovery of an Opioid κ Receptor Selective Pure Antagonist from a Library of N-Substituted 4β-Methyl-5-(3-hydroxyphenyl)morphans
  作者：James B. Thomas、Robert N. Atkinson、Nivedita Namdev、Richard B. Rothman、Kenneth M. Gigstad、Scott E. Fix、S. Wayne Mascarella、Jason P. Burgess、N. Ariane Vinson、Heng Xu、Christina M. Dersch、Buddy E. Cantrell、Dennis M. Zimmerman、F. Ivy Carroll

  DOI：10.1021/jm020084h

  日期：2002.8.1

  A library of compounds biased toward opioid receptor antagonist activity was prepared by incorporating N-phenylpropyl-4p-methyl-5-(3-hydroxyphenyl)morphans as the core scaffold using simultaneous solution phase synthetic methodology. From this library, N-phenylpropyl-4beta-methyl-5-(3-hydroxyphenyl)-7alpha-[3-(1-piperidinyl)propanamido]morphan [(-)-3b] was identified as the first potent and selective k opioid receptor antagonist from the 5-phenylmorphan class of opioids.
• Highly Potent and Selective Phenylmorphan-Based Inverse Agonists of the Opioid δ Receptor
  作者：James B. Thomas、Li Zhang、Hernán A. Navarro、F. Ivy Carroll

  DOI：10.1021/jm060459p

  日期：2006.9.1

  We recently reported the discovery of (+)-5-( 3-hydroxyphenyl)-4-methyl-2-( 3-phenylpropyl)-2-azabicyclo-[ 3.3.1] non-7-yl-( 1-phenyl-1-cyclopentane) carboxamide [(+)-KF4, (+)-5] as a novel chemotype possessing potent antagonist activity at the delta opioid receptor. Additional SAR studies involving changes to both the 2-amino and 7-amido N-substituents using this same (+)- morphan scaffold have revealed compounds with improved potency and selectivity for the delta opioid receptor. The highly potent and selective 2,2-dimethylphenylacetamide analogue (+)- N-[( 1S, 4R, 5R, 7S)-5-( 3-hydroxyphenyl)-4-methyl- 2-(3-phenylpropyl)2- azabicyclo[ 3.3.1] non-7-yl]-2-methyl-2-phenylpropanamide ( 13d, delmorphan-A) showed picomolar inhibitory potency ( K-e = 0.1 nM) in the [ S-35] GTP gamma S functional assay with delta opioid receptor selectivity ratios of 103- and 132- fold versus the mu and kappa opioid receptors, respectively. The compounds showed no agonist activity at any of the three opioid receptors; however, measurements of delta inverse agonist activity within this series illustrated a broad range of negative efficacy and IC50 values 650-fold more potent than the prototypical delta opioid receptor inverse agonist ICI 174 864 ( 22).