11-pentanoyloxy-N-n-propylnoraporphine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: 11-pentanoyloxy-N-n-propylnoraporphine
• 英文别名: R(-)-11-O-valeryl-N-propyl-noraporphine；11-Valeryloxynoraporphine；[(6aR)-6-propyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-yl] pentanoate
• 化学式: C₂₄H₂₉NO₂
• 分子量: 363.5
• InChiKey: JGCVBGVDWQJTDF-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  11-pentanoyloxy-N-n-propylnoraporphine 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 R(-)-N-n-propyl-11-valeryloxynoraporphine hydrochloride
  参考文献：
  名称：

  [EN] R(-)-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF
  [FR] DERIVES DE R(20051222GAO Y ET AL: "Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine.", J MED CHEM., vol. 31, 1988, pages 1392 - 1396, XP002992383GAO Y ET ALSynthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine.J MED CHEM.19883113921396XXGRANCHELLI FE ET AL: "Aporphines. 23. Normorphothebaine derivatives: Synthesis of an aporphine nitrogen mustard.", J ORG CHEM., vol. 42, 1977, pages 2014 - 2017, XP002992384GRANCHELLI FE ET ALAporphines. 23. Normorphothebaine derivatives: Synthesis of an aporphine nitrogen mustard.J ORG CHEM.19774220142017XX

  摘要：

  公开号：

  WO2005099702A3
• 作为产物：
  描述：

  (R)-(-)-11-hydroxy-N-n-propylnoraporphine 、 正戊酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到11-pentanoyloxy-N-n-propylnoraporphine
  参考文献：
  名称：

  N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D2 and serotonin 5-HT1A receptor dual ligands

  摘要：

  A small series of N-propylnoraporphin-11-O-yl carboxylic esters with variant ester lengths were synthesized and their binding potencies at dopamine receptors (D(1), D(2)) and serotonin receptors (5-HT(1A), 5HT(2A)) were evaluated. Monoesters 3a-f showed binding potency of 100 nM or less for the D(2) receptor, and potency of 10 -30 nM for the 5-HT(1A) receptor. Butyryl ester 3d was found to be the best compound possessing the highest potency for both receptors, with K(i) values of 55 and 12 nM for D(2) and 5-HT(1A) receptors, respectively. There is no correlation between the binding potency and the length of the monoesters, but the diesters 9 and 10 were inactive for the D(2) receptor. The dual binding profile of these monoesters for the D(2) and 5-HT(1A) receptors may be useful for the treatment of neuropsychiatric disorders. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.056

文献信息

• Synthesis and neuropharmacological evaluation of R(−)-N-alkyl-11-hydroxynoraporphines and their esters
  作者：Csaba Csutoras、Ao Zhang、Kehong Zhang、Nora S. Kula、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1016/j.bmc.2004.04.029

  日期：2004.7

  We synthesized several N-substituted-11-hydroxynoraporphines and their esters of varying chain length, evaluated their binding affinity at dopamine (DA) receptor sites in rat caudate-putamen membranes, and quantified their effects on motor activity in normal adult male rats. The 11-hydroxyaporphines showed similar neuropharmacological properties to the corresponding 10,11-catecholaporphines. At moderate doses, their esters proved to have more prolonged behavioral actions and superior oral bioavailability. (C) 2004 Elsevier Ltd. All rights reserved.
• [EN] R(-)-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF<br/>[FR] DERIVES DE R(<supplemental>20051222</supplemental>GAO Y ET AL: "Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine.", J MED CHEM., vol. 31, 1988, pages 1392 - 1396, XP002992383GAO Y ET ALSynthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine.J MED CHEM.19883113921396XXGRANCHELLI FE ET AL: "Aporphines. 23. Normorphothebaine derivatives: Synthesis of an aporphine nitrogen mustard.", J ORG CHEM., vol. 42, 1977, pages 2014 - 2017, XP002992384GRANCHELLI FE ET ALAporphines. 23. Normorphothebaine derivatives: Synthesis of an aporphine nitrogen mustard.J ORG CHEM.19774220142017XX
  申请人：MCLEAN HOSPITAL CORP

  公开号：WO2005099702A3

  公开（公告）日：2005-12-22
• N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D2 and serotonin 5-HT1A receptor dual ligands
  作者：Zhili Liu、Xuetao Chen、Peihua Sun、Leiping Yu、Xuechu Zhen、Ao Zhang

  DOI：10.1016/j.bmc.2008.08.056

  日期：2008.9

  A small series of N-propylnoraporphin-11-O-yl carboxylic esters with variant ester lengths were synthesized and their binding potencies at dopamine receptors (D(1), D(2)) and serotonin receptors (5-HT(1A), 5HT(2A)) were evaluated. Monoesters 3a-f showed binding potency of 100 nM or less for the D(2) receptor, and potency of 10 -30 nM for the 5-HT(1A) receptor. Butyryl ester 3d was found to be the best compound possessing the highest potency for both receptors, with K(i) values of 55 and 12 nM for D(2) and 5-HT(1A) receptors, respectively. There is no correlation between the binding potency and the length of the monoesters, but the diesters 9 and 10 were inactive for the D(2) receptor. The dual binding profile of these monoesters for the D(2) and 5-HT(1A) receptors may be useful for the treatment of neuropsychiatric disorders. (C) 2008 Elsevier Ltd. All rights reserved.