17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-6,7-2',3'-indolomorphinan | 221103-41-9

• 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: 17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-6,7-2',3'-indolomorphinan
• 英文别名: [(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2-hydroxy-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: 221103-41-9
• 化学式: C₃₃H₃₂N₂O₅S
• 分子量: 568.693
• InChiKey: NRMYWAHAMIXEGV-OUDZLNJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-6,7-2',3'-indolomorphinan 在 三乙酰氧基硼氢化钠 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.25h， 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：

  17-环丙基甲基-6,7-去氢-4,5-环氧-3,14-二羟基-6,7,2',3'-吲哚并吗喃 、 对甲苯磺酰氯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以79%的产率得到17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3-(p-tosyloxy)-14-hydroxy-6,7-2',3'-indolomorphinan
  参考文献：
  名称：

  N1'-([18F] 氟乙基)naltrindole ([18F]FEtNTI) 的合成：一种用于 δ 阿片受体正电子发射断层扫描研究的放射性配体

  摘要：

  N1'-([ 18 F] 氟乙基) naltrindole ([ 18 F] FEtNTI) 是δ 阿片受体拮抗剂naltrindole (NTI) 的一种新型类似物，已准备好作为放射性配体用于正电子发射断层扫描。用于放射性标记的前体由盐酸纳曲酮分四步获得，总产率为 47%。甲苯磺酸盐离去基团被[ 18 F]氟化物亲核置换，然后氢解（H 2 ，10% Pd/C）酚部分上的苄基保护基团，得到[ 18 F]FEtNTI。放射合成、HPLC 纯化和制剂的平均 (n = 5) 时间是从轰击结束后 77 分钟。获得了高放射化学纯度的[ 18 F]FEtNTI，合成结束时的平均比活为846 mCi/μmol，平均放射化学产率为10%（未校正衰减）。

  DOI：

  10.1002/(sici)1099-1344(199901)42:1<43::aid-jlcr165>3.0.co;2-2

文献信息

• Indium-Labeled Macrocyclic Conjugates of Naltrindole:  High-Affinity Radioligands for In Vivo Studies of Peripheral δ Opioid Receptors
  作者：Romain A. Duval、Rachel L. Allmon、John R. Lever

  DOI：10.1021/jm0700013

  日期：2007.5.1

  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.
• Synthesis of N1′-([18F]fluoroethyl)naltrindole ([18F]FEtNTI): a radioligand for positron emission tomographic studies of delta opioid receptors
  作者：William B. Mathews、Chris M. Kinter、James Palma、Robert V. Daniels、Hayden T. Ravert、Robert F. Dannals、John R. Lever

  DOI：10.1002/(sici)1099-1344(199901)42:1<43::aid-jlcr165>3.0.co;2-2

  日期：1999.1

  hydrochloride with an overall yield of 47%. Nucleophilic displacement of a tosylate leaving group by [ 18 F]fluoride, followed by hydrogenolysis (H 2 , 10% Pd/C) of a benzyl protecting group on the phenolic moiety, gave [ 18 F]FEtNTI. The average (n = 5) time for radiosynthesis, HPLC purification, and formulation was 77 min from end of bombardment. [ 18 F]FEtNTI of high radiochemical purity was obtained with

  N1'-([ 18 F] 氟乙基) naltrindole ([ 18 F] FEtNTI) 是δ 阿片受体拮抗剂naltrindole (NTI) 的一种新型类似物，已准备好作为放射性配体用于正电子发射断层扫描。用于放射性标记的前体由盐酸纳曲酮分四步获得，总产率为 47%。甲苯磺酸盐离去基团被[ 18 F]氟化物亲核置换，然后氢解（H 2 ，10% Pd/C）酚部分上的苄基保护基团，得到[ 18 F]FEtNTI。放射合成、HPLC 纯化和制剂的平均 (n = 5) 时间是从轰击结束后 77 分钟。获得了高放射化学纯度的[ 18 F]FEtNTI，合成结束时的平均比活为846 mCi/μmol，平均放射化学产率为10%（未校正衰减）。