17-(cyclopropylmethyl)-6,7-didehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-1'-(5''-formylpentyl)indolo[6,7:2',3']morphinan | 938188-28-4

• 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-(cyclopropylmethyl)-6,7-didehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-1'-(5''-formylpentyl)indolo[6,7:2',3']morphinan
• 英文别名: [(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2-hydroxy-11-(6-oxohexyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaen-16-yl] 4-methylbenzenesulfonate
• CAS: 938188-28-4
• 化学式: C₃₉H₄₂N₂O₆S
• 分子量: 666.838
• InChiKey: OJSSXZNSSIOOAJ-QJMCPCMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  48
• 可旋转键数：
  11
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  、 17-(cyclopropylmethyl)-6,7-didehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-1'-(5''-formylpentyl)indolo[6,7:2',3']morphinan 在 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 17-(cyclopropylmethyl)-6,7-didehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-1'-(10'''-[6''-hexyl]-[1''',4''',7''',10'''-tetraazacyclododecane-1''',4''',7'''-triacetic acid])indolo[6,7:2',3']morphinan
  参考文献：
  名称：

  Indium-Labeled Macrocyclic Conjugates of Naltrindole:  High-Affinity Radioligands for In Vivo Studies of Peripheral δ Opioid Receptors

  摘要：

  We have identified a series of hydrophilic indium-labeled DOTA and DO3A conjugates of naltrindole (NTI) that are suited to in vivo studies of peripheral delta opioid receptors. Indium(III) complexes, linked to the indole nitrogen of NTI by six- to nine-atom spacers, display high affinities (0.1-0.2 nM) and excellent selectivities for binding to delta sites in vitro. The [In-111]-labeled complexes can be prepared in good isolated yields (similar to 65%) with high specific radioactivities (> 3300 mCi/mu mol). The spacers serve as pharmacokinetic modifiers, and log D-7.4 values range from -2.74 to -1.79. These radioligands exhibit a high level of specific binding (75-94%) to delta opioid receptors in mouse gut, heart, spleen, and pancreas in vivo. Uptakes of radioactivity are saturable by the non-radioactive complexes, inhibited by naltrexone, and blocked by NTI. Thus, these radiometal-labeled NTI analogues warrant further study by single-photon emission computed tomography.

  DOI：

  10.1021/jm0700013
• 作为产物：
  描述：

  6-溴己腈 在 sodium hydride 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.25h， 生成 17-(cyclopropylmethyl)-6,7-didehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-1'-(5''-formylpentyl)indolo[6,7:2',3']morphinan
  参考文献：
  名称：

  Indium-Labeled Macrocyclic Conjugates of Naltrindole:  High-Affinity Radioligands for In Vivo Studies of Peripheral δ Opioid Receptors

  摘要：

  We have identified a series of hydrophilic indium-labeled DOTA and DO3A conjugates of naltrindole (NTI) that are suited to in vivo studies of peripheral delta opioid receptors. Indium(III) complexes, linked to the indole nitrogen of NTI by six- to nine-atom spacers, display high affinities (0.1-0.2 nM) and excellent selectivities for binding to delta sites in vitro. The [In-111]-labeled complexes can be prepared in good isolated yields (similar to 65%) with high specific radioactivities (> 3300 mCi/mu mol). The spacers serve as pharmacokinetic modifiers, and log D-7.4 values range from -2.74 to -1.79. These radioligands exhibit a high level of specific binding (75-94%) to delta opioid receptors in mouse gut, heart, spleen, and pancreas in vivo. Uptakes of radioactivity are saturable by the non-radioactive complexes, inhibited by naltrexone, and blocked by NTI. Thus, these radiometal-labeled NTI analogues warrant further study by single-photon emission computed tomography.

  DOI：

  10.1021/jm0700013