Naltrexone derivative | 90663-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: Naltrexone derivative
• 英文别名: (4R,4aS,7S,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxyspiro[2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7,5'-imidazolidine]-2',4'-dione
• CAS: 90663-78-8
• 化学式: C₂₂H₂₅N₃O₅
• 分子量: 411.458
• InChiKey: AXFDDKKRVFMVHY-OFAZKWMESA-N

物化性质

• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Naltrexone derivative 在 盐酸 作用下， 反应 120.0h， 以42%的产率得到17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-6α-aminomorphinan-6β-carboxamide
  参考文献：
  名称：

  Opioid Antagonist Activity of Naltrexone-Derived Bivalent Ligands:  Importance of a Properly Oriented Molecular Scaffold To Guide “Address” Recognition at κ Opioid Receptors

  摘要：

  The presence of a molecular scaffold to orient a basic group is important for potent and selective kappa opioid antagonist selectivity. An attempt to determine how the geometry of the scaffold affects this selectivity has led to the synthesis of a bivalent ligand (5) whose linker constrains the N17' basic nitrogen (the ''address'') to a position that is 6.5 Angstrom from N17' in the kappa antagonist norBNI (1) when these molecules are superimposed. The fact that compound 5 was found to be a highly selective and potent mu-selective antagonist supports the idea that the position of N17' in 5 precludes effective ion pairing with the nonconserved residue Glu297 on outer loop 3 of the kappa opioid receptor. The high mu receptor binding affinity and in vitro pharmacological selectivity of 5 coupled with its presumed low central nervous system bioavailability suggest that it may be a useful antagonist for the investigation of peripheral mu opioid receptors.

  DOI：

  10.1021/jm950807f
• 作为产物：
  描述：

  氰化钾 、 纳曲酮 在 ammonium hydroxide 、 氯化铵 作用下， 以 甲醇 、 水 为溶剂， 反应 144.0h， 以18.5%的产率得到
  参考文献：
  名称：

  Opioid Antagonist Activity of Naltrexone-Derived Bivalent Ligands:  Importance of a Properly Oriented Molecular Scaffold To Guide “Address” Recognition at κ Opioid Receptors

  摘要：

  The presence of a molecular scaffold to orient a basic group is important for potent and selective kappa opioid antagonist selectivity. An attempt to determine how the geometry of the scaffold affects this selectivity has led to the synthesis of a bivalent ligand (5) whose linker constrains the N17' basic nitrogen (the ''address'') to a position that is 6.5 Angstrom from N17' in the kappa antagonist norBNI (1) when these molecules are superimposed. The fact that compound 5 was found to be a highly selective and potent mu-selective antagonist supports the idea that the position of N17' in 5 precludes effective ion pairing with the nonconserved residue Glu297 on outer loop 3 of the kappa opioid receptor. The high mu receptor binding affinity and in vitro pharmacological selectivity of 5 coupled with its presumed low central nervous system bioavailability suggest that it may be a useful antagonist for the investigation of peripheral mu opioid receptors.

  DOI：

  10.1021/jm950807f

文献信息

• Opioid Antagonist Activity of Naltrexone-Derived Bivalent Ligands:  Importance of a Properly Oriented Molecular Scaffold To Guide “Address” Recognition at κ Opioid Receptors
  作者：MariaLaura Bolognesi、William H. Ojala、William B. Gleason、Jane F. Griffin、Francine Farouz-Grant、Dennis L. Larson、Akira E. Takemori、Philip S. Portoghese

  DOI：10.1021/jm950807f

  日期：1996.1.1

  The presence of a molecular scaffold to orient a basic group is important for potent and selective kappa opioid antagonist selectivity. An attempt to determine how the geometry of the scaffold affects this selectivity has led to the synthesis of a bivalent ligand (5) whose linker constrains the N17' basic nitrogen (the ''address'') to a position that is 6.5 Angstrom from N17' in the kappa antagonist norBNI (1) when these molecules are superimposed. The fact that compound 5 was found to be a highly selective and potent mu-selective antagonist supports the idea that the position of N17' in 5 precludes effective ion pairing with the nonconserved residue Glu297 on outer loop 3 of the kappa opioid receptor. The high mu receptor binding affinity and in vitro pharmacological selectivity of 5 coupled with its presumed low central nervous system bioavailability suggest that it may be a useful antagonist for the investigation of peripheral mu opioid receptors.