tert-butyl (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-7-{[(1-phenyl-1-cyclopentyl)carbonyl]amino}-2-azabicyclo[3.3.1]nonane-2-carboxylate | 911423-02-4

• 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: tert-butyl (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-7-{[(1-phenyl-1-cyclopentyl)carbonyl]amino}-2-azabicyclo[3.3.1]nonane-2-carboxylate
• 英文别名: tert-butyl (1S,4R,5R,7S)-4-methyl-7-[(1-phenylcyclopentanecarbonyl)amino]-5-(3-propan-2-yloxyphenyl)-2-azabicyclo[3.3.1]nonane-2-carboxylate
• CAS: 911423-02-4
• 化学式: C₃₅H₄₈N₂O₄
• 分子量: 560.777
• InChiKey: SCJBPZDIANOQMG-NQLORTQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-7-{[(1-phenyl-1-cyclopentyl)carbonyl]amino}-2-azabicyclo[3.3.1]nonane-2-carboxylate 在 氢溴酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 63.0h， 生成 (+)-N-{(1S,4R,5R,7S)-5-(3-hydroxyphenyl)-4-methyl-2-[3-(2-methylphenyl)prop-2-en-1-yl]-2-azabicyclo[3.3.1]non-7-yl}-1-phenylcyclopentanecarboxamide
  参考文献：
  名称：

  Highly Potent and Selective Phenylmorphan-Based Inverse Agonists of the Opioid δ Receptor

  摘要：

  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).

  DOI：

  10.1021/jm060459p
• 作为产物：
  描述：

  tert-butyl (1S,4R,5R,7S)-7-(1,3-dioxoisoindol-2-yl)-4-methyl-5-(3-propan-2-yloxyphenyl)-2-azabicyclo[3.3.1]nonane-2-carboxylate 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.5h， 生成 tert-butyl (1S,4R,5R,7S)-5-(3-isopropoxyphenyl)-4-methyl-7-{[(1-phenyl-1-cyclopentyl)carbonyl]amino}-2-azabicyclo[3.3.1]nonane-2-carboxylate
  参考文献：
  名称：

  Highly Potent and Selective Phenylmorphan-Based Inverse Agonists of the Opioid δ Receptor

  摘要：

  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).

  DOI：

  10.1021/jm060459p