17-cyclopropylmethyl-4,5α-epoxy-14-hydroxy-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]-morphinan-6-one | 155732-90-4

• 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-14-hydroxy-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]-morphinan-6-one
• 英文别名: 17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]-morphinan-6-one；(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-(1-phenyltetrazol-5-yl)oxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 155732-90-4
• 化学式: C₂₇H₂₇N₅O₄
• 分子量: 485.542
• InChiKey: SSAIAGQCSVOGMK-JXHGYLODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  17-cyclopropylmethyl-4,5α-epoxy-14-hydroxy-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]-morphinan-6-one 在 吡啶 、 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 32.0h， 生成 17-cyclopropylmethyl-8,14-didehydro-4,5α-epoxymorphinan-6-spiro-2'-(1',3'-dioxolane)
  参考文献：
  名称：

  Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists

  摘要：

  The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the delta opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the 8 receptor over the mu receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the 5 receptor in the [S-35]GTPyS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the delta receptor among the morphinan derivatives, the agonist activity toward the delta receptor was the most potent for candidates with the 3-hydroxy group. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.047
• 作为产物：
  描述：

  5-氯-1-苯基-1H-四唑 、 盐酸纳曲酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 以100%的产率得到17-cyclopropylmethyl-4,5α-epoxy-14-hydroxy-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]-morphinan-6-one
  参考文献：
  名称：

  Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists

  摘要：

  The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the delta opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the 8 receptor over the mu receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the 5 receptor in the [S-35]GTPyS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the delta receptor among the morphinan derivatives, the agonist activity toward the delta receptor was the most potent for candidates with the 3-hydroxy group. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.047

文献信息

• Verifying the role of 3-hydroxy of 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(4′-pyridyl) carboxamido]morphinan derivatives via their binding affinity and selectivity profiles on opioid receptors
  作者：Boshi Huang、Rama Gunta、Huiqun Wang、Mengchu Li、Danni Cao、Rolando E. Mendez、James C. Gillespie、Chongguang Chen、Lan-Hsuan M. Huang、Lee-Yuan Liu-Chen、Dana E. Selley、Yan Zhang

  DOI：10.1016/j.bioorg.2021.104702

  日期：2021.4

  series of epoxymorphinan derivatives in their binding affinity and selectivity profiles toward the opioid receptors (ORs) has been investigated. It was found that the 3-hydroxy group was crucial for the binding affinity of these derivatives for all three ORs due to the fact that all the analogues 1a-e exhibited significantly higher binding affinities compared to their counterpart 3-dehydroxy ones 6a-e

  在本研究中，已经研究了一系列环氧吗啡喃衍生物的 3-羟基在其对阿片受体 (OR) 的结合亲和力和选择性曲线中的作用。发现 3-羟基对于这些衍生物对所有三种 OR 的结合亲和力至关重要，因为所有类似物1a-e与其对应的 3-脱羟基化合物6a-e相比表现出显着更高的结合亲和力。同时，大多数带有 3-羟基基团的化合物对 kappa 阿片受体与 mu 阿片受体相比具有与其相应的 3-脱羟基衍生物相似的选择性特征。[ 35S]-GTPγS 功能测定结果表明，这些环氧吗啡喃衍生物的 3-羟基对于维持其对 ORs 的效力具有多种作用。进一步的分子建模研究有助于理解化合物1c ( NCP ) 与其 3-脱羟基类似物6c之间显着不同的结合亲和力和功能特征。
• Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives
  作者：Hitoshi Kubota、Richard B Rothman、Chris Dersch、Karen McCullough、Julia Pinto、Kenner C Rice

  DOI：10.1016/s0960-894x(98)00105-x

  日期：1998.4

  The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable delta selectivity with that of NTI, all of the novel compounds possessed low affinity for delta receptors indicating the important role of the 3-oxygen atom of NTI for

  使用钯催化的转化合成了纳曲多（NTI）的3-个未取代和取代的类似物，并确定了它们与阿片受体的结合亲和力。尽管3-脱氧类似物显示出与NTI相当的δ选择性，但是所有新化合物对δ受体具有低亲和力，表明NTI的3-氧原子对于与δ-阿片样物质受体相互作用具有重要作用。
• Stereoselective syntheses of 3-dehydroxynaltrexamines and N-methyl-3-dehydroxynaltrexamines
  作者：Mengchu Li、Celsey M. St. Onge、Yan Zhang

  DOI：10.1016/j.tetlet.2020.152379

  日期：2020.9

  Methodology is presented for the synthesis of 6α/β-3-dehydroxynaltrexamines and 6α/β-N-methyl-3-dehydroxynaltrexamines. A stereoselective route is provided for each target compound while a novel one-pot method for the synthesis of 6α/β-N-methyl-3-dehydroxynaltrexamines is also explored. These results enable the versatile and efficient preparation of key epoxymorphinan intermediates to facilitate future

  介绍了合成 6 α / β -3-脱羟基 naltrexamines 和 6 α / β - N -methyl-3-dehydroxynaltrexamines 的方法。为每个目标化合物提供了立体选择性路线，同时还探索了一种新的一锅法合成 6 α / β - N -甲基-3-脱羟基纳曲胺。这些结果使关键环氧吗啡喃中间体的多功能和高效制备成为可能，以促进未来选择性阿片类配体的发现和开发。
• Essential structure of opioid κ receptor agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano)phenanthrene derivatives and their pharmacologies
  作者：Hiroshi Nagase、Satomi Imaide、Shigeto Hirayama、Toru Nemoto、Hideaki Fujii

  DOI：10.1016/j.bmcl.2012.05.122

  日期：2012.8

  To clarify the essential structures of an opioid kappa receptor selective agonist, nalfurafine, for binding to the kappa receptor, we designed and synthesized some nalfurafine derivatives and the decahydro(iminoethano)phenanthrene derivatives with a cyclohexene moiety as a surrogate for the phenol ring. In addition to the 6-amide side chain and the 17-nitrogen substituted by a cyclopropylmethyl group, the 4,5-epoxy ring, phenolic hydroxy group, and angular hydroxy group played important roles in eliciting the binding properties of nalfurafine but these three moieties were not indispensable for binding to the kappa receptor. Moreover, the phenol ring was also not essential for the binding to the kappa receptor, and the cyclohexene moiety would play an important role in fixing the conformation of decahydro(iminoethano) phenanthrene derivatives to effectively raise the amide side chain, rendering a conformation that resembled the active one of nalfurafine. (C) 2012 Elsevier Ltd. All rights reserved.
• Krassnig, Roland; Schmidhammer, Helmut, Heterocycles, 1994, vol. 38, # 4, p. 877 - 882
  作者：Krassnig, Roland、Schmidhammer, Helmut

  DOI：——

  日期：——