17-(cyclopropylmethyl)-4,5α-epoxy-17β-hydroxy-3-(methoxymethoxy)benzofuro[2',3':6,7]morphinan | 173782-83-7

• 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)-4,5α-epoxy-17β-hydroxy-3-(methoxymethoxy)benzofuro[2',3':6,7]morphinan
• 英文别名: (1S,2S,13R,21R)-22-(cyclopropylmethyl)-16-(methoxymethoxy)-11,14-dioxa-22-azaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaen-2-ol
• CAS: 173782-83-7
• 化学式: C₂₈H₂₉NO₅
• 分子量: 459.542
• InChiKey: ULKUFQNJSVIECG-CSZVXOJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-17β-hydroxy-3-(methoxymethoxy)benzofuro[2',3':6,7]morphinan 在 盐酸 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 (1S,2S,13R,21R)-22-(cyclopropylmethyl)-2-ethoxy-11,14-dioxa-22-azaheptacyclo[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-ol
  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：

  溴甲基甲基醚 、 17-(环丙基甲基)-6,7-二氢-3,14β-二羟基-4,5α-环氧-6,7-2'，3'-苯并[b]呋喃吗啡喃甲酸酯 在 sodium hydride 作用下， 生成 17-(cyclopropylmethyl)-4,5α-epoxy-17β-hydroxy-3-(methoxymethoxy)benzofuro[2',3':6,7]morphinan
  参考文献：
  名称：

  新型和高效合成的选择性δ阿片受体拮抗剂系列中的14-烷氧基取代的吲哚-和苯并呋喃吗啡喃。

  摘要：

  据报道，使用甲氧基甲基或甲硅烷基保护基，从纳曲酮（1）或纳曲本（2）开始的三个步骤中，新颖且更有效地合成了14-烷氧基取代的吲哚-和苯并呋喃-吗啡喃。在该方法的倒数第二个步骤中引入14- O-烷基。这是所描述的方法的另一个优点，因为较晚引入的14- O-烷基基团使得在该系列δ阿片受体拮抗剂中更容易产生更大多样性的14-烷氧基衍生物。因此，化合物14 - 19，20 - 25，和27 - 29 被合成。

  DOI：

  10.1002/hlca.19980810532

文献信息

• 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.
• A Novel and Efficient Synthesis of 14-Alkoxy-Substituted Indolo- and Benzofuromorphinans in the Series of Selective ? Opioid Receptor Antagonists
  作者：Helmut Schmidhammer、Peter Schwarz、Zhong-Yong Wei

  DOI：10.1002/hlca.19980810532

  日期：——

  A novel and more efficient synthesis of 14-alkoxy-substituted indolo- and benzofuro-morphinans in three steps starting from either naltrindole (1) or naltriben (2), using methoxymethyl or silyl protecting groups, is reported. The 14-O-alkyl group is introduced at the penultimate step of the procedure. This is an additional advantage of the described procedure since the late introduction of the 14-O-alkyl

  据报道，使用甲氧基甲基或甲硅烷基保护基，从纳曲酮（1）或纳曲本（2）开始的三个步骤中，新颖且更有效地合成了14-烷氧基取代的吲哚-和苯并呋喃-吗啡喃。在该方法的倒数第二个步骤中引入14- O-烷基。这是所描述的方法的另一个优点，因为较晚引入的14- O-烷基基团使得在该系列δ阿片受体拮抗剂中更容易产生更大多样性的14-烷氧基衍生物。因此，化合物14 - 19，20 - 25，和27 - 29 被合成。