17-(cyclopropylmethyl)-6,7-didehydro-3,14β-dihydroxy-4,5α-epoxy-6,7-2',3'-(N-methyl-4',5',6',7'-tetrahydroindolo)morphinan | 133042-75-8

• 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-3,14β-dihydroxy-4,5α-epoxy-6,7-2',3'-(N-methyl-4',5',6',7'-tetrahydroindolo)morphinan
• 英文别名: 17-cyclopropylmethyl-6,7-didehydro-3,14-dihydroxy-4,5α-epoxy-1'-methyl-4',5',6',7'-tetrahydroindolo[2',3':6,7]morphinan；(1S,2S,13R,21R)-22-(cyclopropylmethyl)-11-methyl-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),15,17,19(25)-pentaene-2,16-diol
• CAS: 133042-75-8
• 化学式: C₂₇H₃₂N₂O₃
• 分子量: 432.563
• InChiKey: FFTBXBGJNXJGQT-NVSKSXHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  57.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  纳曲酮 在 4 A molecular sieve 、 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 生成 17-(cyclopropylmethyl)-6,7-didehydro-3,14β-dihydroxy-4,5α-epoxy-6,7-2',3'-(N-methyl-4',5',6',7'-tetrahydroindolo)morphinan
  参考文献：
  名称：

  取代对四氢萘并吲哚，四氢氧基吗啉和相关的4,5-环氧苯基吡咯并吗啡喃衍生物中吡咯N原子的影响。

  摘要：

  在四氢萘并三唑（TNTI），四氢吗啉吲哚（TOMI）和17-环丙基甲基-3,14-二羟基-4,5-环氧-4'-苯基-6,7中吡咯和N原子的取代作用：报道了2'，3'-吡咯并吗啡（4）。在阿片样物质功能测定中，有4种是有效的deltaopioid受体（DOR）拮抗剂，而TNTI衍生物（7）是有效的DOR拮抗剂或低效DOR部分激动剂，没有明显的选择性。TOMI衍生物（8）是具有明显选择性的DOR激动剂。在体内证实了7d的DOR拮抗剂活性，但8d的主要激动剂作用是由μ阿片受体介导的。

  DOI：

  10.1021/jm040817t

文献信息

• Role of spacer and address components in peptidomimetic .delta.-opioid receptor antagonists related to naltrindole
  作者：P. S. Portoghese、H. Nagase、K. E. MaloneyHuss、C. E. Lin、A. E. Takemori

  DOI：10.1021/jm00109a027

  日期：1991.5

  A series of heterocyclic analogues 2-5 related to naltrindole (1) (NTI) and 6-arylnaltrexone derivatives 6-8 were synthesized in order to determine the role of the spacer and the address moieties in conferring delta opioid receptor antagonist activity. The benzofuran (NTB), quinoxaline, and quinoline analogues (2, 3, and 4, respectively) were delta-selective opioid antagonists in vitro and bound selectively to delta receptors. The tetrahydroindole derivative 5, while delta-selective, was considerably less potent than its indole analogue 13. The data for 2-4 indicate that heterocycles other than pyrrole can serve as a spacer for the delta address moiety. Moreover, the lower delta antagonist potency of 5 illustrates the importance of the aromatic address component. Molecular dynamics simulations of enkephalin using a zipper binding model are consistent with a delta address subsite that may accommodate the benzene moiety of NTI or the Phe4 phenyl group of leucine enkephalin. The considerably lower delta opioid receptor antagonist potencies of the 6-aryl derivatives 6-8 are consistent with the conformational mobility of the aryl group and its location in the molecule.