17-(cyclopropylmethyl)-6,7-didehydro-3,14β-dihydroxy-4,5α-epoxy-6,7-2',3'-quinoxalinomorphinan | 122431-17-8

• 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'-quinoxalinomorphinan
• 英文别名: (1S,2S,14R,22R)-23-(cyclopropylmethyl)-15-oxa-5,12,23-triazaheptacyclo[14.9.1.01,14.02,22.04,13.06,11.020,26]hexacosa-4,6,8,10,12,16,18,20(26)-octaene-2,17-diol
• CAS: 122431-17-8
• 化学式: C₂₆H₂₅N₃O₃
• 分子量: 427.503
• InChiKey: KASNFNADFKDSTB-IFKAHUTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  78.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (4R,4aS,6Z,7aR,12bS)-9-[tert-butyl(dimethyl)silyl]oxy-3-(cyclopropylmethyl)-4a-hydroxy-6-hydroxyimino-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one 生成 17-(cyclopropylmethyl)-6,7-didehydro-3,14β-dihydroxy-4,5α-epoxy-6,7-2',3'-quinoxalinomorphinan
  参考文献：
  名称：

  PORTOGHESE, PHILIP S.

  摘要：

  DOI：

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.