ガランタミン
カタログ番号:
B1674398
CAS番号:
357-70-0
分子量:
287.35 g/mol
InChIキー:
ASUTZQLVASHGKV-JDFRZJQESA-N
注意:
研究専用です。人間または獣医用ではありません。
概要
説明
作用機序
科学的研究の応用
生化学分析
Biochemical Properties
Galanthamine inhibits the degradation of neurotransmitters acetylcholine (ACh) by binding to the enzyme, acetylcholinesterase (AChE) which is responsible for degrading ACh . The resulting accumulation of ACh caused by galanthamine leads to increased neurotransmission causing continuous stimulation of the muscles, glands .
Cellular Effects
The increased neurotransmission caused by galanthamine can have various effects on cells. It can influence cell function by impacting cell signaling pathways and gene expression. It can also affect cellular metabolism by altering the levels of neurotransmitters in the cell .
Molecular Mechanism
Galanthamine exerts its effects at the molecular level through its binding interactions with acetylcholinesterase. By inhibiting this enzyme, galanthamine prevents the degradation of acetylcholine, leading to an increase in the levels of this neurotransmitter. This can result in changes in gene expression and cellular function .
Temporal Effects in Laboratory Settings
The effects of galanthamine can change over time in laboratory settings. Information on the product’s stability, degradation, and any long-term effects on cellular function observed in in vitro or in vivo studies is currently being researched .
Dosage Effects in Animal Models
The effects of galanthamine can vary with different dosages in animal models. Studies are being conducted to determine any threshold effects observed in these studies, as well as any toxic or adverse effects at high doses .
Metabolic Pathways
Galanthamine is involved in various metabolic pathways. It interacts with enzymes such as acetylcholinesterase and can affect metabolic flux or metabolite levels .
Transport and Distribution
Research is ongoing to determine how galanthamine is transported and distributed within cells and tissues. This includes studying any transporters or binding proteins that it interacts with, as well as any effects on its localization or accumulation .
Subcellular Localization
The subcellular localization of galanthamine and any effects on its activity or function are currently being researched. This includes studying any targeting signals or post-translational modifications that direct it to specific compartments or organelles .
準備方法
合成経路と反応条件: ガランタミンは、生体模倣酸化カップリング反応、遷移金属触媒反応、転位反応など、様々な方法で合成できます . 主要な合成戦略としては、以下のようなものがあります。
酸化フェノールカップリング: この方法は、フェノールの酸化カップリングを利用したものであり、ガランタミンの全合成において広く研究されています.
遷移金属触媒反応: ヘック反応、エニン環化メタセシス（RCM）、動的キネティック分解などがあります.
工業的製造方法: ガランタミンの工業的製造には、天然源からの抽出または合成による製造が用いられます. 最初の工業プロセスは1959年に開発されました . 近年では、収率向上やコスト削減を目指して、合成経路の最適化が進んでおり、 .
化学反応の分析
反応の種類: ガランタミンは、以下のような様々な化学反応を起こします。
一般的な試薬と条件:
主要な生成物: これらの反応によって生成される主要な生成物には、官能基が修飾された様々なガランタミン誘導体が含まれており、薬理作用が異なる場合があります .
類似化合物との比較
特性
IUPAC Name |
(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-ol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C17H21NO3/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17/h3-6,12,14,19H,7-10H2,1-2H3/t12-,14-,17-/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
ASUTZQLVASHGKV-JDFRZJQESA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CN1CCC23C=CC(CC2OC4=C(C=CC(=C34)C1)OC)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
CN1CC[C@@]23C=C[C@@H](C[C@@H]2OC4=C(C=CC(=C34)C1)OC)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C17H21NO3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID2045606 |
Source
|
| Record name | Galanthamine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2045606 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
287.35 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Galantamine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014812 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
Crystals from water; decomposition 256-257 °C. Sparingly sol in cold; more sol in hot water. Very sparingly sol in alcohol, acetone. /Hydrochloride/, Fairly soluble in hot water; freely soluble in alcohol, acetone, chloroform. Less sol in benzene, ether., 1.70e+00 g/L |
Source
|
| Record name | GALANTAMINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7361 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Galantamine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014812 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Mechanism of Action |
Alzheimer’s disease is characterized by progressive, irreversible degeneration of acetylcholine-producing neurons, cognitive impairment, and the accumulation of neurofibrillary tangles and amyloid plaques. The cholinergic system plays a critical role in memory, alongside other important neural functions such as attention, learning, stress response, wakefulness and sleep, and sensory information. Studies show that acetylcholine (ACh) is involved in the modulation of acquisition, encoding, consolidation, reconsolidation, extinction, and retrieval of memory. The gradual loss of cholinergic neurons in Alzheimer’s disease (AD) may, therefore, contribute to the memory loss exhibited by AD patients. Acetylcholinesterase is secreted by cholinergic neurons to rapidly hydrolyze ACh at the synaptic cleft to release acetate and choline. Choline is later recycled back into the presynaptic cholinergic neuron via reuptake by the high-affinity choline transporter. There is some evidence demonstrating the potential involvement of the acetylcholinesterase enzyme in the formation of amyloid fibrils. Galantamine competitively and reversibly inhibits the anticholinesterase enzyme in the CNS (namely in the frontal cortex and hippocampal regions) by binding to the choline-binding site and acyl-binding pocket of the enzyme active site. By blocking the breakdown of ACh, galantamine enhances ACh levels in the synaptic cleft. Nicotinic acetylcholine receptors (nAChR) in the CNS are mostly expressed at the presynaptic neuronal membrane to control the release of multiple neurotransmitters, such as ACh, glutamate, GABA, dopamine, serotonin, norepinephrine. Agonists of nAChRs improve performance in cognitive tasks, while antagonists of nAChR impair cognitive processes. Some studies show a decrease in the expression and activity of nAChRs in patients with AD, which may explain the reduction in central cholinergic neurotransmission in these patients. Galantamine binds to nAChRs at the allosteric site, leading to a conformational change of the receptor, increased ACh release, and increased activity of neighbouring glutaminergic and serotoninergic neurons. The modulation of nAChRs facilitates both excitatory and inhibitory cholinergic transmissions in brain tissues and increases receptor sensitivity. The modulated release of other neurotransmitters by galantamine may also contribute to the upregulation of nAChRs and amelioration of behavioural symptoms in AD., Galantamine, a tertiary alkaloid, is a competitive and reversible inhibitor of acetylcholinesterase. While the precise mechanism of galantamine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this mechanism is correct, galantamine's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine alters the course of the underlying dementing process., The cause of cognitive impairment in Alzheimer's Disease is not fully understood, it has been shown that acetylcholine producing neurons degenerate. The cholinergic loss has been correlated with cognitive impairment and a density of amyloid plaques. Galantamine is a tertiary alkaloid and it competes with and is a reversible inhibitor of acetylcholinesterase. The exact mechanism of galantamine is not known, but it is believed to enhance cholinergic function. |
Source
|
| Record name | Galantamine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00674 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | GALANTAMINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7361 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Color/Form |
Crystals from benzene | |
CAS No. |
357-70-0, 23173-12-8 |
Source
|
| Record name | (-)-Galantamine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=357-70-0 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Galantamine [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000357700 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | (+/-)-Galantamine | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0023173128 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Galantamine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00674 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Galantamine | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=759861 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | Galanthamine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2045606 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | GALANTAMINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/0D3Q044KCA | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | GALANTAMINE, (±)- | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/1T835Z585R | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | GALANTAMINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7361 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Galantamine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014812 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Melting Point |
126-127 °C, 269 - 270 °C (hydrogen bromide salt) |
Source
|
| Record name | GALANTAMINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7361 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Galantamine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014812 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Synthesis routes and methods I
Procedure details
(-)-Narwedine (>98% ee, 0.1 g) was added to a mixture of lithium aluminium hydride (1.2 ml of a 1.0 M solution in ether), (-)-N-methylephedrine (0.23 g) and N-ethyl-2-aminopyridine (0.31 g) in ether at 0° C., and the resulting mixture was stirred at that temperature for 4 h. Sodium hydroxide solution (10 ml of a 1.0 M solution) was added and the product extracted with dichloromethane. Evaporation of the organic phase gave (-)-galanthamine (>98% ee, 85% yield) free of epigalanthamine by GC/MS analysis.
[Compound]
Name
solution
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Two
[Compound]
Name
solution
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
Name
Yield
85%
Synthesis routes and methods II
Procedure details
Lithium aluminium hydride (1M in ether, 1.2 ml, 1.20 mmol) was placed in a two necked round bottom flask fitted with a reflux condenser and nitrogen inlet. (-)-N-methy-ephedrine (0.23 g, 1.26 mmol) in ether (1 ml) was added dropwise and the solution was heated at reflux for 1 hour then cooled to room temperature. N-Ethyl-2-aminopyridine (0.31g, 2.52 mmol) in ether (1 ml) was added and the bright yellow solution was heated under reflux for a further 1 hour. The solution was cooled to -78° C. and solid (+) narwedine (97% e.e) (0.10 g, 0.35 mmol) was added. The suspension was warmed to 0° C., stirred for 20 hours and then allowed to warm to room temperature over 1 hour. The reaction was quenched 2M potassium carbonate (10 ml). The mixture was extracted into ethyl acetate (2×10 ml) and then the combined organic layer was washed with water (5 ml) and brine (5 ml) and dried over magnesium sulphate. Filtration and evaporation gave an orange oil which was shown by NMR and GC-MS to contain galanthamine and epigalanthamine in a 1:1 mixture. Flash chromatography on silica in dichloromethane-methanol 10:1 yielded (+) galanthamine (98% e.e.) (30% yield) and (+)-epigalanthamine (95% e.e) (26% yield). ##STR3##
Name
dichloromethane methanol
Quantity
0 (± 1) mol
Type
solvent
Reaction Step One
[Compound]
Name
(-)-N-methy-ephedrine
Quantity
0.23 g
Type
reactant
Reaction Step Three
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
Reactant of Route 1
galanthamine
Reactant of Route 2
galanthamine
Reactant of Route 3
galanthamine
Reactant of Route 4
galanthamine
Reactant of Route 5
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Reactant of Route 6
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試験管内研究製品の免責事項と情報
BenchChemで提示されるすべての記事および製品情報は、情報提供を目的としています。BenchChemで購入可能な製品は、生体外研究のために特別に設計されています。生体外研究は、ラテン語の "in glass" に由来し、生物体の外で行われる実験を指します。これらの製品は医薬品または薬として分類されておらず、FDAから任何の医療状態、病気、または疾患の予防、治療、または治癒のために承認されていません。これらの製品を人間または動物に体内に導入する形態は、法律により厳格に禁止されています。これらのガイドラインに従うことは、研究と実験において法的および倫理的な基準の遵守を確実にするために重要です。
![[(1s)-1-Isothiocyanatoethyl]benzene](/img/structure/B1674335.png)
