(4R,4aS,7R,7aR,12bS)-7-(methylamino)-3-(2-methylpropyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol | 1417030-51-3

• 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,7R,7aR,12bS)-7-(methylamino)-3-(2-methylpropyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
• CAS: 1417030-51-3
• 化学式: C₂₁H₃₀N₂O₃
• 分子量: 358.481
• InChiKey: IUQWEWRWMUYCLN-GQHLEUQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  65
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7R,7aR,12bS)-7-(methylamino)-3-(2-methylpropyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol 、 3-(furan-3-yl)acryloyl chloride 在 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 生成 N-[(4R,4aS,7R,7aR,12bS)-4a,9-dihydroxy-3-(2-methylpropyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylprop-2-enamide
  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：

  6β-N-methylnaltrexamine 在 盐酸 、 platinum(IV) oxide 作用下， 以 水 为溶剂， 以100%的产率得到(4R,4aS,7R,7aR,12bS)-7-(methylamino)-3-(2-methylpropyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
  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

• MORPHINAN DERIVATIVE AND MEDICINAL USE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0663401A1

  公开（公告）日：1995-07-19

  A morphinan derivative represented by formula (1) or a pharmacologically acceptable acid-addition salt thereof, and analgesic, diuretic, antitussive and brain cell protective agents each containing the derivative or the salt as the active ingredient. These compounds have potent analgesic, diuretic and antitussive effects as a highly selective κ-opioid agonist, and are useful as analgesic, diuretic and antitussive agents. In addition, they have a significant brain cell protective effect and are useful as a brain cell protective agent.

  由式（1）代表的吗啡南衍生物或其药理学上可接受的酸加成盐，以及含有该衍生物或盐作为活性成分的镇痛剂、利尿剂、镇咳剂和脑细胞保护剂。这些化合物作为一种高选择性κ-类阿片激动剂，具有强效的镇痛、利尿和镇咳作用，可用作镇痛、利尿和镇咳制剂。此外，它们还具有明显的脑细胞保护作用，可用作脑细胞保护剂。
• US6177438B1
  申请人：——

  公开号：US6177438B1

  公开（公告）日：2001-01-23