norbinaltorphimine | 114375-44-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: norbinaltorphimine
• 英文别名: (1S,2S,7R,8R,12S,20S,24R,32R)-11,33-bis(cyclopropylmethyl)-19,25-dioxa-11,22,33-triazaundecacyclo[24.9.1.18,14.01,24.02,32.04,23.05,21.07,12.08,20.030,36.018,37]heptatriaconta-4(23),5(21),14(37),15,17,26,28,30(36)-octaene-2,7,17,27-tetrol
• CAS: 114375-44-9
• 化学式: C₄₀H₄₃N₃O₆
• 分子量: 661.798
• InChiKey: APSUXPSYBJVPPS-XFPGJURKSA-N

物化性质

• 密度：
  1.63±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  49
• 可旋转键数：
  4
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  122
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  盐酸纳曲酮 、 (+)-naltrexone hydrochloride 在 1-amino-pyrrolidine-2,5-dione; hydrochloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以46.9%的产率得到(+/-)-norbinaltorphimine
  参考文献：
  名称：

  Stereochemical studies on medicinal agents. 31. Only one pharmacophore is required for the .kappa. opioid antagonist selectivity of norbinaltorphimine

  摘要：

  We have investigated whether one or two pharmacophores are required for the kappa opioid receptor selectivity of the bivalent opioid antagonist norbinaltorphimine, (-)-1 (nor-BNI), by the synthesis and testing of its meso isomer 2. In smooth muscle preparations 2 was more potent than 1 and about half as selective as a kappa antagonist. Since 2 contains only one antagonist pharmacophore but yet retains substantial kappa selectivity, it is concluded that kappa selectivity is not dependent on the presence of two (-)-naltrexone-derived pharmacophores of 1. It is suggested that the kappa selectivity of (-)-1 and 2 is derived from the portions of the second halves of these molecules in that they mimic key "address" components of dynorphin at kappa opioid receptors.

  DOI：

  10.1021/jm00402a015