1-[(4'R,4'aS,7'aR,12'bS)-4'a-hydroxy-9'-methoxyspiro[1,3-dioxolane-2,7'-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline]-3'-yl]-2,2-difluoroethanone | 1417030-52-4

• 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: 1-[(4'R,4'aS,7'aR,12'bS)-4'a-hydroxy-9'-methoxyspiro[1,3-dioxolane-2,7'-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline]-3'-yl]-2,2-difluoroethanone
• CAS: 1417030-52-4
• 化学式: C₂₁H₂₃F₂NO₆
• 分子量: 423.414
• InChiKey: VVZGZNTZAPXHSV-NWTFUFRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[(4'R,4'aS,7'aR,12'bS)-4'a-hydroxy-9'-methoxyspiro[1,3-dioxolane-2,7'-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline]-3'-yl]-2,2-difluoroethanone 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 生成
  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：

  二氟乙酸乙酯 、 14β-hydroxy-17-nor-dihydrocodeinone ethylene ketal 在 三甲基铝 作用下， 以 二氯甲烷 为溶剂， 以51%的产率得到1-[(4'R,4'aS,7'aR,12'bS)-4'a-hydroxy-9'-methoxyspiro[1,3-dioxolane-2,7'-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline]-3'-yl]-2,2-difluoroethanone
  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] MEMORY-IMPROVING AGENT AND USE THEREOF<br/>[FR] AGENT AMÉLIORANT LA MÉMOIRE ET SON UTILISATION<br/>[JA] 記憶改善剤及びその使用
  申请人：SCHOOL JURIDICAL PERSON KITASATO INST

  公开号：WO2016167318A1

  公开（公告）日：2016-10-20

  　オピオイドδ受容体のインバースアゴニストである化合物、その薬学的に許容される塩、又はそれらの溶媒和物を有効成分として含有する記憶改善剤及び記憶改善用組成物、下記式（５）で表される化合物、その薬学的に許容される塩、又はそれらの溶媒和物。