(4R,4aS,7R,7aR,12bS)-7-[benzyl(methyl)amino]-9-methoxy-3-propyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol | 1417030-65-9

• 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: (4R,4aS,7R,7aR,12bS)-7-[benzyl(methyl)amino]-9-methoxy-3-propyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol
• CAS: 1417030-65-9
• 化学式: C₂₈H₃₆N₂O₃
• 分子量: 448.605
• InChiKey: SLOONLIMHHUEDS-DNOLTMOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7R,7aR,12bS)-7-[benzyl(methyl)amino]-9-methoxy-3-propyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以50%的产率得到(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 、 对甲苯磺酸 、 苯甲酸 作用下， 以 甲醇 、 水 、 苯 为溶剂， 生成 (4R,4aS,7R,7aR,12bS)-7-[benzyl(methyl)amino]-9-methoxy-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