4,5α-epoxy-3-hydroxy-5β,17-dimethyl-14β-propoxymorphinan-6-one | 173683-01-7

• 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: 4,5α-epoxy-3-hydroxy-5β,17-dimethyl-14β-propoxymorphinan-6-one
• 英文别名: 4,5α-epoxy-3-hydroxy-5,17-dimethyl-14-n-propyloxymorphinan-6-one；(4R,4aS,7aR,12bR)-9-hydroxy-3,7a-dimethyl-4a-propoxy-1,2,4,5,6,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 173683-01-7
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: HUXLSMGJKVNXQR-PSOYPTMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯肼,盐酸盐 、 4,5α-epoxy-3-hydroxy-5β,17-dimethyl-14β-propoxymorphinan-6-one 以 溶剂黄146 为溶剂， 反应 20.0h， 以0.36 g的产率得到4,5α-epoxy-5β,17-dimethyl-14β-propoxy-1'H-indolo[2',3':6,7]morphinan-3-ol hydrochloride
  参考文献：
  名称：

  Novel Delta-Opioid-Receptor-Selective Ligands in the 14-Alkoxy-Substituted Indolo- and Benzofuromorphinan Series

  摘要：

  Several new indolo- and benzofuromorphinans substituted at the positions 5 and 14 were prepared and tested in vitro by means of opioid-receptor binding and functional ([(35)S]GTP gammaS binding) assays. All compounds 1-11 displayed high affinity for delta opioid-binding sites (Table 1). Compound 4 proved to be an agonist, and all other compounds were antagonists. The presence of a Me group at position 5 induced no change in delta affinity (see 1 vs. 3), but decreased the mu and kappa affinities. An EtO group at position 14 conferred a very high affinity and also high selectivity to delta opioid receptors (see 2 and 10). Chain elongation of the 14-alkoxy group resulted in compounds with reduced delta affinity and selectivity (see 4 and 11 and also 5-9). The results of the present study indicate that the 5- and 14-positions of indolo- and benzofuromorphinans represent critical sites that could be a trigger to develop new compounds with increased delta affinity and/or selectivity.

  DOI：

  10.1002/1522-2675(20010711)84:7<2015::aid-hlca2015>3.0.co;2-1
• 作为产物：
  描述：

  4,5α-epoxy-3-methoxy-5β,17-dimethyl-14β-propoxymorphinan-6-one 在 三溴化硼 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 以57%的产率得到4,5α-epoxy-3-hydroxy-5β,17-dimethyl-14β-propoxymorphinan-6-one
  参考文献：
  名称：

  Novel Delta-Opioid-Receptor-Selective Ligands in the 14-Alkoxy-Substituted Indolo- and Benzofuromorphinan Series

  摘要：

  Several new indolo- and benzofuromorphinans substituted at the positions 5 and 14 were prepared and tested in vitro by means of opioid-receptor binding and functional ([(35)S]GTP gammaS binding) assays. All compounds 1-11 displayed high affinity for delta opioid-binding sites (Table 1). Compound 4 proved to be an agonist, and all other compounds were antagonists. The presence of a Me group at position 5 induced no change in delta affinity (see 1 vs. 3), but decreased the mu and kappa affinities. An EtO group at position 14 conferred a very high affinity and also high selectivity to delta opioid receptors (see 2 and 10). Chain elongation of the 14-alkoxy group resulted in compounds with reduced delta affinity and selectivity (see 4 and 11 and also 5-9). The results of the present study indicate that the 5- and 14-positions of indolo- and benzofuromorphinans represent critical sites that could be a trigger to develop new compounds with increased delta affinity and/or selectivity.

  DOI：

  10.1002/1522-2675(20010711)84:7<2015::aid-hlca2015>3.0.co;2-1

文献信息

• NEW AGONIST COMPOUNDS
  申请人：Astra Aktiebolag

  公开号：EP0759923A1

  公开（公告）日：1997-03-05
• US5886001A
  申请人：——

  公开号：US5886001A

  公开（公告）日：1999-03-23
• [EN] NEW AGONIST COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES AGONISTES
  申请人：ASTRA AKTIEBOLAG

  公开号：WO1995031464A1

  公开（公告）日：1995-11-23

  (EN) New morphinane derivatives of formula (I), their pharmaceutically acceptable salts, a process for their preparation and their use in therapy.(FR) Nouveaux dérivés de morphinane représentés par la formule (I), leurs sels pharmaceutiquement acceptables, procédé servant à leur préparation et leur utilisation thérapeutique.
• Novel Delta-Opioid-Receptor-Selective Ligands in the 14-Alkoxy-Substituted Indolo- and Benzofuromorphinan Series
  作者：Dauren Biyashev、Krisztina Monory、Sandor Benyhe、Johannes Schütz、Martin Koch、Helmut Schmidhammer、Anna Borsodi

  DOI：10.1002/1522-2675(20010711)84:7<2015::aid-hlca2015>3.0.co;2-1

  日期：2001.7.11

  Several new indolo- and benzofuromorphinans substituted at the positions 5 and 14 were prepared and tested in vitro by means of opioid-receptor binding and functional ([(35)S]GTP gammaS binding) assays. All compounds 1-11 displayed high affinity for delta opioid-binding sites (Table 1). Compound 4 proved to be an agonist, and all other compounds were antagonists. The presence of a Me group at position 5 induced no change in delta affinity (see 1 vs. 3), but decreased the mu and kappa affinities. An EtO group at position 14 conferred a very high affinity and also high selectivity to delta opioid receptors (see 2 and 10). Chain elongation of the 14-alkoxy group resulted in compounds with reduced delta affinity and selectivity (see 4 and 11 and also 5-9). The results of the present study indicate that the 5- and 14-positions of indolo- and benzofuromorphinans represent critical sites that could be a trigger to develop new compounds with increased delta affinity and/or selectivity.