17,17'-dimethyl-6,6',7,7'-tetrahydro-4,5:4',5'-diepoxy-6,6'-(imino)-[7,7'-bimorphinan]-3,3',14,14'-tetrol

• 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: 17,17'-dimethyl-6,6',7,7'-tetrahydro-4,5:4',5'-diepoxy-6,6'-(imino)-[7,7'-bimorphinan]-3,3',14,14'-tetrol
• 英文别名: (1S,2S,7S,8S,12R,20R,24R,32R)-11,33-dimethyl-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
• 化学式: C₃₄H₃₅N₃O₆
• 分子量: 581.668
• InChiKey: ASOVJVGZJDVADR-UCDXVGGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  43
• 可旋转键数：
  0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  122
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  溴甲苯 、 17,17'-dimethyl-6,6',7,7'-tetrahydro-4,5:4',5'-diepoxy-6,6'-(imino)-[7,7'-bimorphinan]-3,3',14,14'-tetrol 在 18-冠醚-6 、 sodium hydride 、 氢溴酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以80%的产率得到17,17'-dimethyl-6,6',7,7'-tetrahydro-4,5:4',5'-diepoxy-6,6'-(benzylimino)[7,7'-bimorphinan]-3,3',14,14'-tetrol
  参考文献：
  名称：

  Major Effect of Pyrrolic N-Benzylation in Norbinaltorphimine, the Selective κ-Opioid Receptor Antagonist

  摘要：

  Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly their MOR activity. When administered systemically in mouse antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of relatively short duration whereas on central administration it had only a KOR-antagonist action of extremely long duration.

  DOI：

  10.1021/jm049172n
• 作为产物：
  描述：

  氢羟吗啡酮 在 肼 、 甲烷磺酸 作用下， 以 N,N-二甲基甲酰胺 、 二甲基亚砜 为溶剂， 生成 17,17'-dimethyl-6,6',7,7'-tetrahydro-4,5:4',5'-diepoxy-6,6'-(imino)-[7,7'-bimorphinan]-3,3',14,14'-tetrol
  参考文献：
  名称：

  Major Effect of Pyrrolic N-Benzylation in Norbinaltorphimine, the Selective κ-Opioid Receptor Antagonist

  摘要：

  Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly their MOR activity. When administered systemically in mouse antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of relatively short duration whereas on central administration it had only a KOR-antagonist action of extremely long duration.

  DOI：

  10.1021/jm049172n

文献信息

• METHODS FOR THE CHEMICAL SYNTHESIS OF PYRROLE-LINKED BIVALENT COMPOUNDS, AND COMPOSITIONS THEREOF
  申请人：AVEKSHAN LLC

  公开号：US20180072747A1

  公开（公告）日：2018-03-15

  The present invention in various aspects relates to the synthesis of pyrrole-linked bivalent compounds, including but not limited to norBNI, as well as pharmaceutical compositions comprising the same.
• Major Effect of Pyrrolic N-Benzylation in Norbinaltorphimine, the Selective κ-Opioid Receptor Antagonist
  作者：Cédric Chauvignac、Carl N. Miller、Sanjay K. Srivastava、John W. Lewis、Stephen M. Husbands、John R. Traynor

  DOI：10.1021/jm049172n

  日期：2005.3.1

  Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly their MOR activity. When administered systemically in mouse antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of relatively short duration whereas on central administration it had only a KOR-antagonist action of extremely long duration.