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N-去甲基加兰它敏氢溴酸盐 | 41303-74-6

中文名称
N-去甲基加兰它敏氢溴酸盐
中文别名
N-去甲基加兰他敏;氮位N-脱甲基加兰他敏;N-去甲加兰他敏(加兰他敏杂质E)
英文名称
N-desmethyl galantamine
英文别名
norgalanthamine;N-demethylgalanthamine;norgalantamine;N-norgalanthamine;N-Demethylgalantamine;(1S,12S,14R)-9-methoxy-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-ol
N-去甲基加兰它敏氢溴酸盐化学式
CAS
41303-74-6
化学式
C16H19NO3
mdl
——
分子量
273.332
InChiKey
AIXQQSTVOSFSMO-RBOXIYTFSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    142-145°C
  • 沸点:
    457.9±45.0 °C(Predicted)
  • 密度:
    1.30±0.1 g/cm3(Predicted)
  • 溶解度:
    可溶于DMSO

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

ADMET

代谢
N-去甲基加兰他敏加兰他敏在人身体内已知的一种代谢物。
N-desmethylgalantamine is a known human metabolite of galantamine.
来源:NORMAN Suspect List Exchange

安全信息

  • 储存条件:
    存储条件:2-8°C,需密封并保持干燥。

SDS

SDS:515f084d24ab893c92185b7b001a70c6
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制备方法与用途

生物活性方面,N-去甲基化卡克兰宁(N-Desmethyl Galanthamine)是卡克兰宁(Galanthamine)的代谢物。卡克兰宁是一种有效的乙酰胆碱酯酶(AChE)抑制剂,其IC50值为500 nM。

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6

反应信息

  • 作为反应物:
    描述:
    N-去甲基加兰它敏氢溴酸盐 在 lithium aluminium tetrahydride 作用下, 以 四氢呋喃 为溶剂, 反应 55.0h, 生成 加兰他敏
    参考文献:
    名称:
    (+/-)-加兰他敏的仿生合成和使用远程不对称诱导的(-)-加兰他敏的不对称合成。
    摘要:
    (+/-)-加兰他敏(1)通过应用PIFA介导的N-(4-羟基)苯乙基-N-(3',4',5'-三烷氧基)苄基甲酰胺( 15b)作为关键步骤。由于底物(15b)中邻苯三酚部分的对称特性,苯酚偶合产生唯一的偶合产物,除了氧化剂的挥发性成分。根据上述策略的成功结果,采用新颖的远程不对称诱导合成(-)-加兰他敏(1),其中苯酚偶联产物中的七元环构象通过形成在三-O-烷基化的胆酰基氨基部分的苄基CN键上具有D-苯丙氨酸的稠合手性咪唑啉酮环。
    DOI:
    10.1248/cpb.54.1662
  • 作为产物:
    参考文献:
    名称:
    Galantamine Derivatives as Acetylcholinesterase Inhibitors: Docking, Design, Synthesis, and Inhibitory Activity
    摘要:
    加兰他敏 (GAL) 是一种众所周知的乙酰胆碱酯酶 (AChE) 抑制剂,广泛用于治疗阿尔茨海默病。GAL 在 AChE 的催化位点中契合良好,但它的长度不足以阻断酶的周边阴离子位点 (PAS),而该位点是淀粉样β (Aβ) 肽结合并启动 Aβ 聚集的地方。在这里,我们描述了一种基于对接的技术,用于设计具有双重位点结合片段的 GAL 衍生物——一个阻断催化位点,另一个阻断 PAS。我们合成并测试了评分高的化合物。本文提供了对接、设计、合成和 AChE 抑制测试的协议。
    DOI:
    10.1007/978-1-4939-7404-7_6
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文献信息

  • [EN] DUAL TARGETING COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] COMPOSÉS À DOUBLE CIBLAGE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
    申请人:UNIV BOLOGNA ALMA MATER
    公开号:WO2013160728A1
    公开(公告)日:2013-10-31
    Compounds of formula (I) wherein the groups are as defined in the description, are used as medicaments, in particular for the treatment of a disease selected from the group consisting of: cognitive impairment, memory dysfunction, neurodegenerative disorders and related dementia, Alzheimer's disease, Parkinson's disease, neuropsychiatric behavior associated with Alzheimer's disease, pain, depression, attention deficit hyperactivity disorder and for pharmacological addictive substance or intoxicant therapy; and for the neuroprotection from NMDA toxicity.
    式(I)中的化合物,其中所述的基团如描述中定义的那样,被用作药物,特别用于治疗从以下组中选择的疾病:认知障碍,记忆功能障碍,神经退行性疾病及相关痴呆症,阿尔茨海默病,帕森病,与阿尔茨海默病相关的神经精神行为,疼痛,抑郁症,注意力缺陷多动障碍,以及用于药理学成瘾物质或中毒物质治疗;以及用于对抗NMDA毒性的神经保护。
  • Galantamine-Curcumin Hybrids as Dual-Site Binding Acetylcholinesterase Inhibitors
    作者:Georgi Stavrakov、Irena Philipova、Atanas Lukarski、Mariyana Atanasova、Dimitrina Zheleva、Zvetanka D. Zhivkova、Stefan Ivanov、Teodora Atanasova、Spiro Konstantinov、Irini Doytchinova
    DOI:10.3390/molecules25153341
    日期:——

    Galantamine (GAL) and curcumin (CU) are alkaloids used to improve symptomatically neurodegenerative conditions like Alzheimer’s disease (AD). GAL acts mainly as an inhibitor of the enzyme acetylcholinesterase (AChE). CU binds to amyloid-beta (Aβ) oligomers and inhibits the formation of Aβ plaques. Here, we combine GAL core with CU fragments and design a combinatorial library of GAL-CU hybrids as dual-site binding AChE inhibitors. The designed hybrids are screened for optimal ADME properties and BBB permeability and docked on AChE. The 14 best performing compounds are synthesized and tested in vitro for neurotoxicity and anti-AChE activity. Five of them are less toxic than GAL and CU and show activities between 41 and 186 times higher than GAL.

    盖兰他敏(GAL)和姜黄素(CU)是用来改善像阿尔茨海默病(AD)这样的神经退行性疾病症状的生物碱。GAL主要作为乙酰胆碱酯酶(AChE)的抑制剂。CU结合到淀粉样蛋白β(Aβ)寡聚体并抑制Aβ斑块的形成。在这里,我们将GAL的核心与CU的片段结合,设计了一个GAL-CU杂交物的组合库,作为双位结合AChE抑制剂。设计的杂交物被筛选出具有最佳的ADME性能和血脑屏障透过性,并在AChE上进行对接。表现最佳的14种化合物被合成并在体外进行神经毒性和抗AChE活性测试。其中五种化合物比GAL和CU更少毒,并且显示出比GAL高41到186倍的活性。
  • Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity
    作者:Mariyana Atanasova、Georgi Stavrakov、Irena Philipova、Dimitrina Zheleva、Nikola Yordanov、Irini Doytchinova
    DOI:10.1016/j.bmc.2015.07.058
    日期:2015.9
    compounds were synthesized and tested for inhibitory activity. All of them were between 11 and 95 times more active than galantamine. The novel galantamine derivatives with indole moiety have dual site binding to the enzyme—the galantamine moiety binds to the catalytic anionic site and the indole moiety binds to peripheral anionic site. Additionally, the indole moiety of one of the novel inhibitors binds
    乙酰胆碱酯酶抑制剂是对抗阿尔茨海默氏病的主要疗法。其中,加兰他敏是耐受性最好,处方最明确的药物。在本研究中,从文献中选择了以IC 50表示的具有已知乙酰胆碱酯酶抑制活性的41种加兰他敏生物,并通过GOLD插入重组乙酰胆碱酯酶中。GoldScores和pIC 50之间的线性关系发现其值并用于设计和预测在侧链中具有吲哚部分的新型加兰他敏生物。合成了四种最佳预测化合物,并测试了其抑制活性。它们的活性都比加兰他敏高11至95倍。具有吲哚部分的新型加兰他敏生物具有与酶的双重位点结合-加兰他敏部分与催化阴离子位点结合,而吲哚部分与外围阴离子位点结合。另外,一种新型抑制剂吲哚部分在靠近该酶的外围阴离子位点的区域结合,在该区域淀粉样β肽的Ω-环粘附于乙酰胆碱酯酶。该化合物作为多靶点抗阿尔茨海默病治疗的有前途的领先化合物出现,不仅因为其强大的抑制活性,
  • Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment
    申请人:Galantos Pharma GmbH
    公开号:EP1777222A1
    公开(公告)日:2007-04-25
    The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline of neuronal cholinergic receptors and/or acting as chvlinesterase inhibitors and/or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g. galanthamine, narwedine and lyeoramine, or from metabolites of said compounds. The compounds of the present invention can either interact as such with their target molecules, or they can act as "prodrugs", in the sense that after reaching their target regions in the body they are converted by hydrolysis or enzymatic attack to the original parent compound and react as such with their target molecules, or both. The compounds of this invention may be used as medicaments for the treatment of human brain diseases associated with a cholinergic deficit, including the neurodegenerative diseases Alzheimer's and Parkinson's disease and the psychiatric diseases vascular dementia, schizophrenia and epilepsy.
    本发明涉及化合物,除了增强神经胆碱能受体对乙酰胆碱胆碱的敏感性,或者作为胆碱酯酶抑制剂和/或神经保护剂之外,与其原始化合物相比具有增强的血脑屏障渗透性。这些化合物来源于属于石蒜科生物碱类的天然化合物,例如迎春碱、纳尔韦丁和莱奥拉明,或者来源于这些化合物的代谢物(无论是从化学结构上还是直接通过化学合成)。本发明的化合物可以直接与其靶分子相互作用,或者它们可以作为“前药”,意味着在到达体内的靶区域后,它们通过解或酶攻击转化为原始的母体化合物,并且与其靶分子相互作用,或者两者兼而有之。本发明的化合物可用作治疗与胆碱缺乏相关的人类脑疾病的药物,包括神经退行性疾病阿尔茨海默病和帕森病,以及精神疾病血管性痴呆、精神分裂症和癫痫。
  • Synthesis of3H-,14C-, and stable-isotope-labelled galantamine
    作者:G. M. Janssen、Jos B. A. Thijssen、Willy L. M. Verluyten
    DOI:10.1002/jlcr.589
    日期:2002.9
    Reminyl® is a newly approved drug, used in the treatment of mild to moderate Alzheimer disease. The active compound, galantamine, was initially isolated from the bulbs of certain Narcissus species, but is at the moment also produced synthetically. In the process leading to the final approval, the synthesis of tritium-, carbon-14- and stable-isotope-labelled galantamine for pharmacokinetic studies was required. Racemic (±)-1-bromonarwedine, a compound available as intermediate from the commercial synthesis, was transformed to racemic 1-bromo-galantamine. Catalytic bromo-tritium exchange, followed by HPLC purification and resolution afforded tritium-labelled galantamine. The [14C]-label was introduced on the nitrogen as well as on the oxygen-methyl position. This was achieved by N- and O-demethylation of galantamine and reaction of the thoroughly purified intermediate with [14C]-methyl iodide. Stable-isotope-labelled galantamine was obtained likewise by 13CD3OD-methylation of O-demethylated galantamine under Mitsunobu conditions. Copyright © 2002 John Wiley & Sons, Ltd.
    Reminyl®是一种新近批准的药物,用于治疗轻度至中度的阿尔茨海默病。其活性成分加兰他敏最初是从某些仙属植物的球茎中分离出来的,但目前也通过合成制备。在最终批准的过程中,需要合成氚、碳-14和稳定同位素标记的加兰他敏,用于药代动力学研究。 从商业合成中可获得的中间体化合物外消旋(±)-1-诺华定,被转化为外消旋1-加兰他敏。通过催化-氚交换,随后进行HPLC纯化和拆分,得到了氚标记的加兰他敏。[14C]标记被引入到氮原子上以及氧甲基位置。这是通过加兰他敏的N-和O-去甲基化,以及与[14C]甲基反应,使用充分纯化的中间体实现的。通过在三苯膦条件下使用13CD3OD对O-去甲基化加兰他敏进行甲基化,同样获得了稳定同位素标记的加兰他敏。 版权所有 © 2002 John Wiley & Sons, Ltd.
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