(4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-propyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one | 99307-37-6

• 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: (4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-propyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 99307-37-6
• 化学式: C₂₀H₂₅NO₄
• 分子量: 343.423
• InChiKey: XDVJEVVSCYTYNA-XFWGSAIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 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：

  (4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-propyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one 在 5%-palladium/activated carbon 、 氢气 、 对甲苯磺酸 、 苯甲酸 作用下， 以 甲醇 、 苯 为溶剂， 生成 (4R,4aS,7R,7aR,12bS)-9-methoxy-7-(methylamino)-3-propyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol
  参考文献：
  名称：

  The effect of 17-N substituents on the activity of the opioid κ receptor in nalfurafine derivatives

  摘要：

  We have previously reported the essential structure of the opioid kappa receptor agonist nalfurafine hydrochloride (TRK-820) for binding to the kappa receptor. In the course of this study, we focused on the effect of the substituent at 17-N in nalfurafine on the binding affinity for the j receptor. The exchange of the 17-N substituent in nalfurafine from cyclopropylmethyl to fluoro-substituted alkyl groups, which are strong electron withdrawing substituents, almost completely diminished the binding affinities for the mu and delta opioid receptors, but the binding affinity for the j receptor was still maintained. As a result, nalfurafine derivatives with 17-fluoro-substituted alkyl groups showed higher selectivities for the j receptor than did nalfurafine itself. With regard to the j agonistic activities, the conversion of the 17-N substituent in nalfurafine from cyclopropylmethyl to fluoro-substituted alkyl groups led to the gradual decrease of the agonistic activities in the order corresponding to their binding affinities for the j receptor. In contrast, the derivative with the bulky 17-isobutyl group showed lower affinity and agonistic activity for the j receptor than the derivatives with the smaller functional groups. This research suggested that both the electronic property and the steric characteristics of the 17-N substituent would have a great influence on the binding property for the j receptor. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.100
• 作为产物：
  描述：

  (4'R,4'aS,7'aR,12'bS)-9'-methoxy-3'-propylspiro[1,3-dioxolane-2,7'-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline]-4'a-ol 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以96%的产率得到(4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-propyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
  参考文献：
  名称：

  The effect of 17-N substituents on the activity of the opioid κ receptor in nalfurafine derivatives

  摘要：

  We have previously reported the essential structure of the opioid kappa receptor agonist nalfurafine hydrochloride (TRK-820) for binding to the kappa receptor. In the course of this study, we focused on the effect of the substituent at 17-N in nalfurafine on the binding affinity for the j receptor. The exchange of the 17-N substituent in nalfurafine from cyclopropylmethyl to fluoro-substituted alkyl groups, which are strong electron withdrawing substituents, almost completely diminished the binding affinities for the mu and delta opioid receptors, but the binding affinity for the j receptor was still maintained. As a result, nalfurafine derivatives with 17-fluoro-substituted alkyl groups showed higher selectivities for the j receptor than did nalfurafine itself. With regard to the j agonistic activities, the conversion of the 17-N substituent in nalfurafine from cyclopropylmethyl to fluoro-substituted alkyl groups led to the gradual decrease of the agonistic activities in the order corresponding to their binding affinities for the j receptor. In contrast, the derivative with the bulky 17-isobutyl group showed lower affinity and agonistic activity for the j receptor than the derivatives with the smaller functional groups. This research suggested that both the electronic property and the steric characteristics of the 17-N substituent would have a great influence on the binding property for the j receptor. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.100

文献信息

• [EN] PROCESS FOR THE PREPARATION OF MORPHINANE COMPOUNDS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE COMPOSÉS DE MORPHINANE
  申请人：SANECA PHARMACEUTICALS A S

  公开号：WO2019009820A1

  公开（公告）日：2019-01-10

  The invention describes the process of catalytic O-demethylation of 3-methoxy-morphinane compounds using boron tribromide. Addition of catalysts reduces the reaction time, improves reacting the substrate to give the product in very good purity and yield. The said approach can be used, for example, for the preparation of oxymorphone, naltrexone, naloxone and nalbuphine from their respective O-methyl derivatives.

  本发明描述了使用三溴化硼催化剂进行3-甲氧基吗啡烷类化合物的催化O-去甲基化过程。添加催化剂可缩短反应时间，提高底物的反应性，从而以非常高的纯度和收率给出产物。该方法可用于制备羟吗啡酮、纳曲酮、纳洛酮和纳布啡等化合物，这些化合物是从它们各自的O-甲基衍生物制备而来的。
• Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists
  作者：Toru Nemoto、Yusuke Iihara、Shigeto Hirayama、Takashi Iwai、Eika Higashi、Hideaki Fujii、Hiroshi Nagase

  DOI：10.1016/j.bmcl.2015.05.038

  日期：2015.8

  We synthesized derivatives of the delta opioid receptor (DOR) antagonists naltrindole (NTI) and compound 1 that were modified with small alkyl or fluorinated ethyl substituents on the 17-nitrogen. Although the derivatives showed decreased binding affinities for the opioid receptors, their selectivities for the DOR were higher than the parent compounds NTI and compound 1. Surprisingly, 17-fluoroethyl NTI derivatives exerted DOR inverse agonistic activities. The DOR inverse agonism of compounds 4c-e was less efficacious but significant, as compared with a standard DOR inverse agonist ICI-174864. On the other hand, compound 1 and its derivatives with small alkyl or monofluoroethyl substituents were partial agonists, but the derivatives having di- or trifluoroethyl group showed neither agonistic nor inverse agonistic activities. (C) 2015 Elsevier Ltd. All rights reserved.
• PROCESS FOR THE PREPARATION OF MORPHINANE COMPOUNDS
  申请人：Saneca Pharmaceuticals a.s.

  公开号：EP3649131A1

  公开（公告）日：2020-05-13
• [EN] 7,8-CYCLICMORPHINAN ANALOGS<br/>[FR] ANALOGUES DE 7,8-CYCLICMORPHINANE
  申请人：PURDUE PHARMA LP

  公开号：WO2014102587A1

  公开（公告）日：2014-07-03

  The application is directed to compounds of Formula (I), and pharmaceutically acceptable salts and solvates thereof, wherein Cy, R1-R3, R4A, and R4B are defined as set forth in the specification. The invention is also directed to use of compounds of Formula (I) to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the present invention are especially useful for treating pain.