naltrindole-5'-isothiocyanate | 143619-52-7

• 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: naltrindole-5'-isothiocyanate
• 英文别名: 7'-isothiocyanatonaltrindole；5'-NTII；Naltrindole isothiocyanate hydrochloride；(1S,2S,13R,21R)-22-(cyclopropylmethyl)-9-isothiocyanato-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15,17,19(25)-heptaene-2,16-diol
• CAS: 143619-52-7
• 化学式: C₂₇H₂₅N₃O₃S
• 分子量: 471.58
• InChiKey: STOXPPZNSYPOHZ-BQRPEJFJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  盐酸纳曲酮 在 镍 盐酸 、 碳酸氢钠 、 溶剂黄146 、 肼 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 8.5h， 生成 naltrindole-5'-isothiocyanate
  参考文献：
  名称：

  .delta. Opioid antagonist activity and binding studies of regioisomeric isothiocyanate derivatives of naltrindole: evidence for .delta. receptor subtypes

  摘要：

  The isothiocyanate group was attached to the 4'-, 5'-, 6'-, or 7'-position of naltrindole in an effort to determine the importance of the position of this electrophilic group on the selectivity for subtypes of delta opioid receptors. All of the ligands were delta-selective when tested against standard agonists in smooth muscle preparations. However, the rank-order delta antagonism of antinociception in mice did not parallel the in vitro pharmacologic data. The 5'-isothiocyanate 2 was the most potent and selective antagonist in vivo, causing a 52-fold increase of the ED50 for [D-Ser2,D-Leu5]enkephalin-Thr6 (DSLET) and no increase for [D-Pen2,D-Pen5]enkephalin (DPDPE). The effect of each of the ligands on the binding of [H-3]DSLET and [H-3]DPDPE to guinea pig brain membranes clearly differentiated between the binding sites that recognize these radioligands. These studies provide additional evidence for the presence of two subtypes of delta opioid receptors.

  DOI：

  10.1021/jm00100a014

文献信息

• .delta. Opioid antagonist activity and binding studies of regioisomeric isothiocyanate derivatives of naltrindole: evidence for .delta. receptor subtypes
  作者：P. S. Portoghese、M. Sultana、W. L. Nelson、P. Klein、A. E. Takemori

  DOI：10.1021/jm00100a014

  日期：1992.10

  The isothiocyanate group was attached to the 4'-, 5'-, 6'-, or 7'-position of naltrindole in an effort to determine the importance of the position of this electrophilic group on the selectivity for subtypes of delta opioid receptors. All of the ligands were delta-selective when tested against standard agonists in smooth muscle preparations. However, the rank-order delta antagonism of antinociception in mice did not parallel the in vitro pharmacologic data. The 5'-isothiocyanate 2 was the most potent and selective antagonist in vivo, causing a 52-fold increase of the ED50 for [D-Ser2,D-Leu5]enkephalin-Thr6 (DSLET) and no increase for [D-Pen2,D-Pen5]enkephalin (DPDPE). The effect of each of the ligands on the binding of [H-3]DSLET and [H-3]DPDPE to guinea pig brain membranes clearly differentiated between the binding sites that recognize these radioligands. These studies provide additional evidence for the presence of two subtypes of delta opioid receptors.