17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-O-(benzoyloxy)morphinan-6-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-O-(benzoyloxy)morphinan-6-one
• 英文别名: 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-O-(benzoyloxy)morphinan-6-one hydrochloride；[(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl] benzoate;hydrochloride
• 化学式: C₂₇H₂₇NO₅*ClH
• 分子量: 481.976
• InChiKey: SGBQRJWSKVEUBL-PLWHKPGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-O-(benzoyloxy)morphinan-6-one 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-14β-O-(benzoyloxy)morphinan-6-one
  参考文献：
  名称：

  14-O-杂环取代的纳曲酮衍生物作为非肽μ阿片受体选择性拮抗剂：设计、合成和生物学研究

  摘要：

  Mu阿片受体拮抗剂具有临床实用性，是重要的研究工具。为了开发非肽类、高选择性μ阿片受体拮抗剂，设计、合成并评价了一系列14- O-杂环取代的纳曲酮衍生物。这些化合物对μ阿片受体表现出亚纳摩尔至纳摩尔的结合亲和力。其中，化合物1对μ阿片受体相对于δ和κ受体表现出最高的选择性。这些结果表明 mu 阿片受体的细胞外环中有一个替代的“地址”结构域。

  DOI：

  10.1016/j.bmcl.2008.12.093

文献信息

• Design, Synthesis, and Biological Evaluation of 14-Heteroaromatic-Substituted Naltrexone Derivatives: Pharmacological Profile Switch from Mu Opioid Receptor Selectivity to Mu/Kappa Opioid Receptor Dual Selectivity
  作者：Yunyun Yuan、Saheem A. Zaidi、Orgil Elbegdorj、Lindsey C. K. Aschenbach、Guo Li、David L. Stevens、Krista L. Scoggins、William L. Dewey、Dana E. Selley、Yan Zhang

  DOI：10.1021/jm4012214

  日期：2013.11.27

  On the basis of a mu opioid receptor (MOR) homology model and the isosterism concept, three generations of 14-heteroaromatically substituted naltrexone derivatives were designed, synthesized, and evaluated as potential MOR-selective ligands. The first-generation ligands appeared to be MOR-selective, whereas the second and the third generation ones showed MOR/kappa opioid receptor (KOR) dual selectivity. Docking of ligands 2 (MOR selective) and 10 (MOR/KOR dual selective) to the three opioid receptor crystal structures revealed a nonconserved-residue-facilitated hydrogen-bonding network that could be responsible for their distinctive selectivity profiles. The MOR/KOR dual-selective ligand 10 showed no agonism and acted as a potent antagonist in the tail-flick assay. It also produced less severe opioid withdrawal symptoms than naloxone in morphine-dependent mice. In conclusion, ligand 10 may serve as a novel lead compound to develop MOR/KOR dual-selective ligands, which might possess unique therapeutic value for opioid addiction treatment.