(+)-norgalanthamine | 156040-03-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: (+)-norgalanthamine
• 英文别名: Epinorgalanthamine；(1S,12S,14S)-9-methoxy-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-ol
• CAS: 156040-03-8
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: AIXQQSTVOSFSMO-FFSVYQOJSA-N

物化性质

• 沸点：
  457.9±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  三氟甲烷磺酸甲酯 、 N-去甲基加兰它敏氢溴酸盐 、 (+)-norgalanthamine 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 生成 加兰他敏 、 表雪花莲胺碱
  参考文献：
  名称：

  Synthesis and evaluation of (−)- and (+)-[11C]galanthamine as PET tracers for cerebral acetylcholinesterase imaging

  摘要：

  Improved radiopharmaceuticals for imaging cerebral acetylcholinesterase (AChE) are needed for the diagnosis of Alzheimer's disease (AD). Thus, C-11-labeled (-)-galanthamine and its enantiomers were synthesized as novel agents for imaging the localization and activity of AChE by positron emission tomography (PET). C-11 was incorporated into (-)- and (+)-[C-11] galanthamine by N-methylation of norgalanthamines with [C-11] methyl triflate. Simple accumulation of C-11 in the brain was measured in an in vivo biodistribution study using mice, whilst donepezil was used as a blocking agent in analogous in vivo blocking studies. In vitro autoradiography of rat brain tissue was performed to investigate the distribution of (-)-[C-11] galanthamine, and confirmed the results of PET studies in mice. The radiochemical yields of N-methylation of (-)- and (+)-norgalanthamines were 13.7% and 14.4%, respectively. The highest level of accumulation of C-11 in the brains of mice was observed at 10 min after administration (2.1% ID/g). Intravenous pretreatment with donepezil resulted in a 30% decrease in accumulation of (-)-[C-11] galanthamine in the striatum; however, levels in the cerebellum were unchanged. In contrast, use of (+)[ C-11] galanthamine led to accumulation of radioactivity in the striatum equal to that in the cerebellum, and these levels were unaffected by pretreatment with donepezil. In in vitro autoradiography of regional radioactive signals of brain sections showed that pretreatment with either (-)-galanthamine or donepezil blocked the binding of (-)-[C-11] galanthamine to the striatum, while sagittal PET imaging revealed accumulation of (-)-[C-11] galanthamine in the brain. These results indicate that (-)-[C-11] galanthamine showed specific binding to AChE, whereas (+)-[C-11]-galanthamine accumulated in brain tissue by nonspecific binding. Thus, optically pure (-)-[C-11] galanthamine could be a useful PET tracer for imaging cerebral AChE. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.026

文献信息

• VERFAHREN ZUR HERSTELLUNG VON DERIVATEN DES 4A,5,9,10,11,12-HEXAHYDROBENZOFURO [3A,3,2][ 2 ]- BENZAZEPINS
  申请人：Sanochemia Pharmazeutika Aktiengesellschaft

  公开号：EP1667770B1

  公开（公告）日：2009-03-11
• Novel derivatives of 4a,5,9,10,11,12-hexahydrobenzofuro[3a,3,2][2]-benzazepine, method for the production thereof and use thereof in the production of medicaments
  申请人：Czollner Laszlo

  公开号：US20070105837A1

  公开（公告）日：2007-05-10

  The invention relates to novel derivatives of 4a,5,9,10,11,12-hexahydro-benzofuro[3a,3,2] [2]benzazepine of general formulae 1a, 1b and 1c. Compounds 1a, 1b and 1c can be produced in an efficient manner on an industrial scale with the desired optical purity and are suitable for the production of medicaments for the treatment of a diverse range of symptoms, particularly diseases of the central nervous system (CNS), on account of the pharmacological effect thereof.
• [DE] MITTEL ZUM BEEINFLUSSEN DER WIRKUNGEN VON ORGANOPHOSPHORVERBINDUNGEN UND VERWENDUNG VON GALANTHAMIN, DESSEN DERIVATEN UND ANALOGA ZUM HERSTELLEN SOLCHER MITTEL<br/>[EN] COMPOSITIONS FOR INFLUENCING THE EFFECTS OF ORGANOPHOSPHORUS COMPOUNDS AND USE OF GALANTHAMINE, ITS DERIVATIVES AND ANALOGUES FOR PRODUCING SUCH COMPOSITIONS<br/>[FR] AGENT SERVANT À INFLUENCER LES EFFETS DE COMPOSÉS ORGANOPHOSPHORÉS ET UTILISATION DE GALANTHAMINE, DE SES DÉRIVÉS ET ANALOGUES POUR LA FABRICATION D'UN TEL AGENT
  申请人：SANOCHEMIA LTD

  公开号：WO2008022365A2

  公开（公告）日：2008-02-28

  [EN] The use of galanthamine of the formula and derivatives or analogues of galanthamine for controlling the effect of toxic organic phosphorus compounds such as parathion, paraxon, sarin, soman or tabun is described, wherein a composition comprising the said compound or a combination of at least two of the said compounds is administered before and/or after contact of a human with the toxic organic phosphorus compound.
  [FR] L'invention concerne l'utilisation de galanthamine de formule (I) et de dérivés ou d'analogues de galanthamine pour lutter contre les effets de composés de phosphore organiques toxiques, tels que la parathione, la paraxone, le sarin, le soman ou le tabun. Selon l'invention, un agent contenant ledit composé ou une combinaison d'au moins deux desdits composés est administré avant et/ou après le contact d'un humain avec le composé de phosphore organique toxique.
  [DE] Beschrieben wird die Verwendung von Galanthamin der Formel (I) und Derivaten oder Analoga des Galanthamins zum Bekämpfen der Wirkung von giftigen organischen Phosphorverbindungen, wie Parathion, Paraxon, Sarin, Soman oder Tabun, indem ein die genannte Verbindung oder eine Kombination aus wenigstens zwei der genannten Verbindungen enthaltendes Mittel vor und/oder nach dem Kontakt eines Menschen mit der giftigen organischen Phosphorverbindung verabreicht wird.