O-乙酰基加兰它敏 | 25650-83-3

• 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
• 中文名称: O-乙酰基加兰它敏
• 中文别名: 邻乙酰丙胺
• 英文名称: O-acetylgalanthamine
• 英文别名: galanthamine acetate；3β-acetoxy-6-methoxy-10-methyl-galantham-1-ene；3β-Acetoxy-6-methoxy-10-methyl-galantham-1-en；[(1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-yl] acetate
• CAS: 25650-83-3
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: ZTWNMOVEDXUICV-QOKNQOGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 储存条件：
  室温、干燥且密封保存。

制备方法与用途

O-乙酰加兰他敏是一种乙酰化的生物碱，可以从水仙中自然提取得到。

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
  加兰他敏	Galantamine	357-70-0	C17H21NO3	287.359

反应信息

• 作为产物：
  描述：

  乙酰氯 、 加兰他敏 在 吡啶 作用下， 反应 10.0h， 以43.6%的产率得到O-乙酰基加兰它敏
  参考文献：
  名称：

  PROCESS FOR MANUFACTURING EXTREMELY PURE BENZAZEPINE DERIVATIVES

  摘要：

  一种生产极纯的风信子碱或其衍生物的方法，首先从外消旋溴化纳尔维丁开始，通过钯催化去溴化。在这种情况下，反应混合物的处理必须在氧气或过氧化物的存在下进行，以便将钯催化剂转化为易于分离的不溶形式。进一步的反应是将对映纯的纳尔维丁还原成对映纯的风信子碱，然后通过烷基化或去烷基化使环氮原子上发生相应的取代。通过进一步的纯化，如重结晶，可以实现钯的残留量低于5 ppm，从而使其可以直接用作药用原料。

  公开号：

  US20090326219A1

文献信息

• CHOLINERGIC ENHANCERS WITH IMPROVED BLOOD-BRAIN BARRIER PERMEABILITY FOR THE TREATMENT OF DISEASES ACCOMPANIED BY COGNITIVE IMPAIRMENT
  申请人：Maelicke Alfred

  公开号：US20070213318A1

  公开（公告）日：2007-09-13

  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 cholinesterase 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 lycoramine, 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 “pro-drugs”, 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，除了增强神经元胆碱能受体对乙酰胆碱和胆碱的敏感性，或者作为胆碱酯酶抑制剂和/或神经保护剂外，与其母化合物相比，具有增强的血脑屏障渗透性。这些化合物是从天仙子科生物碱类天仙子碱，如无心菜碱、纳尔韦丁和百合碱，或其代谢物中派生的（通过其化学结构或直接通过化学合成）。本发明的化合物可以直接与其目标分子相互作用，也可以作为“前药”，在到达体内目标区域后，通过水解或酶攻击转化为原始母化合物，并像母化合物一样与其目标分子反应，或两者兼而有之。本发明的化合物可用作治疗与胆碱能缺陷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金森病以及精神疾病血管性痴呆、精神分裂症和癫痫。
• Cholinergic Enhancers with Improved Blood-Brain Barrier permeability for the Treatment of Diseases Accompanied by Cognitive Impairment
  申请人：Maelicke Alfred

  公开号：US20080261954A1

  公开（公告）日：2008-10-23

  The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline, and their exogenous agonists, of neuronal cholinergic receptors and/or acting as cholinesterase 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 lycoramine, or from metabolites of said compounds.

  本发明涉及一种化合物，除了增强神经元胆碱能受体及外源性激动剂对乙酰胆碱和胆碱的敏感性，以及作为胆碱酯酶抑制剂和/或神经保护剂外，还具有比其母体化合物更强的血脑屏障通透性。这些化合物是从天仙子科生物碱（例如迎春花碱，纳威丁和莲花碱）或其代谢物中衍生出来的（可以通过其化学结构或直接通过化学合成来实现）。
• Chemical and pharmacological characterization of galanthamine, an acetylcholinesterase inhibitor, and its derivatives. A potential application in Alzheimer's disease?
  作者：SY Han、JE Sweeney、ES Bachman、EJ Schweiger、G Forloni、JT Coyle、BM Davis、MM Joullié

  DOI：10.1016/0223-5234(92)90087-h

  日期：1992.10

  We conducted structural and pharmacological studies of galanthamine, a cortical acetylcholinesterase (AChE) inhibitor, and 19 structural analogs. Systematic derivatization of galanthamine at the cyclohexene ring, tertiary amino, hydroxyl and methoxyl functions indicated that these structural features are essential for biological activity. Molecular modeling studies suggested that the low energy conformations of the analogs are similar to that of the parent. One derivative, galanthamine n-butyl carbamate, had an LD50 of over 100 mg/kg (ip) in mice. In a passive avoidance paradigm, this analog improved performance in a dose-dependent fashion with a peak effect at 0.1 mg/kg in control and 0.5 mg/kg in basal forebrain lesioned mice. In the same paradigm, the peak effect of the parent compound is a 6-fold higher dose. With this surprinsingly high therapeutic ratio, this compound may be of interest in treating cholinergic deficits of the central nervous system such as Alzheimer's disease.
• US9763953B2
  申请人：——

  公开号：US9763953B2

  公开（公告）日：2017-09-19
• PROCESS FOR MANUFACTURING EXTREMELY PURE BENZAZEPINE DERIVATIVES
  申请人：GERDES Klaus

  公开号：US20090326219A1

  公开（公告）日：2009-12-31

  A process for the production of extremely pure galanthamine or extremely pure galanthamine derivatives, a start is made from racemic bromine narwedine, which is debrominated under palladium catalysis. In this case, the working-up of the reaction mixture, which is carried out in the presence of oxygen or peroxides so that the palladium catalyst in an insoluble form is converted into an easily separable form, is essential. The further reaction is carried out by reduction of enantiomer-pure narwedine to form enantiomer-pure galanthamine, whereby it is then alkylated or dealkylated so that a corresponding substitution on the ring-nitrogen atom is achieved. By further purification, such as recrystallization, residual portions of palladium of below 5 ppm are achieved, so that direct use as a pharmaceutical raw material is made possible.

  一种生产极纯的风信子碱或其衍生物的方法，首先从外消旋溴化纳尔维丁开始，通过钯催化去溴化。在这种情况下，反应混合物的处理必须在氧气或过氧化物的存在下进行，以便将钯催化剂转化为易于分离的不溶形式。进一步的反应是将对映纯的纳尔维丁还原成对映纯的风信子碱，然后通过烷基化或去烷基化使环氮原子上发生相应的取代。通过进一步的纯化，如重结晶，可以实现钯的残留量低于5 ppm，从而使其可以直接用作药用原料。