41303-74-6

Usage

Uses

Used in Pharmaceutical Industry:
N-DESMETHYLGALANTHAMINE is used as a therapeutic agent for the treatment of neurodegenerative diseases, particularly Alzheimer's disease. Its selective acetylcholinesterase inhibitory activity helps improve cognitive function and memory by increasing the levels of acetylcholine in the brain.
Used in Research and Development:
N-DESMETHYLGALANTHAMINE is used as a research compound for studying the mechanisms of neurodegenerative diseases and the development of novel therapeutic strategies. Its chemical properties and biological activities make it a valuable tool in the design and synthesis of new drugs targeting acetylcholinesterase.
Used in Drug Delivery Systems:
N-DESMETHYLGALANTHAMINE can be employed in the development of innovative drug delivery systems to enhance its bioavailability, stability, and targeted delivery to the brain. This may involve the use of nanoparticles, liposomes, or other advanced drug delivery technologies to improve the efficacy and safety of N-DESMETHYLGALANTHAMINE-based treatments.

InChI:InChI=1/C16H19NO3/c1-19-12-3-2-10-9-17-7-6-16-5-4-11(18)8-13(16)20-15(12)14(10)16/h2-5,11,13,17-18H,6-9H2,1H3/t11-,13-,16-/m0/s1

Upstream product

• 134332-50-6 galanthamine N-oxide 
• 271769-63-2 C₁₆H₁₇NO₃ 
• 357-70-0 Galantamine 
• 1953-04-4 Galantamine hydrobromide 
• 213984-66-8 (2,2-Diphenyl-6-trimethylsilanyl-benzo[1,3]dioxol-5-yl)-methanol 
• 213984-59-9 2,2-Diphenyl-6-trimethylsilanyl-benzo[1,3]dioxole-5-carbaldehyde 
• 213984-51-1 C₃₃H₃₀F₃NO₄Si 
• 213984-39-5 N-(2,2-Diphenyl-6-trimethylsilanyl-benzo[1,3]dioxol-5-ylmethyl)-2,2,2-trifluoro-N-[2-(4-hydroxy-phenyl)-ethyl]-acetamide 
• 65638-94-0 2,2-diphenylbenzo(1,3-dioxole)-5-carboxylic acid methyl ester 
• 213984-05-5 (6-bromo-2,2-diphenylbenzo[1,3]dioxol-5-yl)methanol 
• 70006-59-6 2,2-Diphenyl-1,3-benzodioxol-5-methanol 
• 2150-43-8 3,4-dihydroxybenzoic acid methyl ester 
• 99-50-3 3,4-Dihydroxybenzoic acid 
• 722499-72-1 (2S,5R)-5-benzyl-2-(3,5-dibenzyloxy-4-methoxyphenyl)-3-[2-(4-hydroxyphenyl)ethyl]-1-(2,2,2-trifluoroacetyl)imidazolidin-4-one 

Downstream Products

• 913380-51-5 10-N-demethyl-10-N-(2-(4-(piperidin-1-ylmethyl)phenoxy)ethan-1-yl)galanthamine 
• 913380-52-6 10-N-demethyl-10-N-(3-(4-(piperidin-1-ylmethyl)phenoxy)propan-1-yl)galanthamine 
• 913380-53-7 10-N-demethyl-10-N-(4-(4-(piperidin-1-ylmethyl)phenoxy)butan-1-yl)galanthamine 
• 913380-54-8 10-N-demethyl-10-N-(5-(4-(piperidin-1-ylmethyl)phenoxy)pentan-1-yl)galanthamine 
• 913380-55-9 10-N-demethyl-10-N-(6-(4-(piperidin-1-ylmethyl)phenoxy)hexan-1-yl)galanthamine 
• 913380-56-0 10-N-demethyl-10-N-(8-(4-(piperidin-1-ylmethyl)phenoxy)octan-1-yl)galanthamine 
• 913380-57-1 10-N-demethyl-10-N-(9-(4-(piperidin-1-ylmethyl)phenoxy)nonan-1-yl)galanthamine 
• 913380-58-2 10-N-demethyl-10-N-(10-(4-(piperidin-1-ylmethyl)phenoxy)decan-1-yl)galanthamine 
• 913380-59-3 10-N-demethyl-10-N-(12-(4-(piperidin-1-ylmethyl)phenoxy)dodecan-1-yl)galanthamine 
• 913380-61-7 10-N-demethyl-10-N-(6-(4-((diethylamino)methyl)phenoxy)hexan-1-yl)galanthamine 
• 913380-62-8 10-N-demethyl-10-N-(4-(4-(morpholino-methyl)phenoxy)butan-1-yl)galanthamine 
• 913380-63-9 10-N-demethyl-10-N-(6-(4-(morpholino-methyl)phenoxy)hexan-1-yl)galanthamine 
• 913380-64-0 10-N-demethyl-10-N-(4-(3-(1-morpholinoethyl)phenoxy)butan-1-yl)galanthamine 
• 913380-65-1 10-N-demethyl-10-N-(6-(3-(1-morpholinoethyl)phenoxy)hexan-1-yl)galanthamine 

Relevant academic research and scientific papers

Galantamine derivatives as acetylcholinesterase inhibitors: Docking, design, synthesis, and inhibitory activity

Galantamine (GAL) is a well-known acetylcholinesterase (AChE) inhibitor, and it is widely used for treatment of Alzheimer’s disease. GAL fits well in the catalytic site of AChE, but it is too short to block the peripheral anionic site (PAS) of the enzyme,

Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity

The inhibitors of acetylcholinesterase are the main therapy against Alzheimer's disease. Among them, galantamine is the best tolerated and the most prescribed drug. In the present study, 41 galantamine derivatives with known acetylcholinesterase inhibitor

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

Improved radiopharmaceuticals for imaging cerebral acetylcholinesterase (AChE) are needed for the diagnosis of Alzheimer's disease (AD). Thus, 11C-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 (+)-[ 11C]galanthamine by N-methylation of norgalanthamines with [ 11C]methyl triflate. Simple accumulation of 11C 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 (-)-[11C]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 11C 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 (-)-[11C]galanthamine in the striatum; however, levels in the cerebellum were unchanged. In contrast, use of (+)-[11C]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 (-)-[11C] galanthamine to the striatum, while sagittal PET imaging revealed accumulation of (-)-[11C]galanthamine in the brain. These results indicate that (-)-[11C]galanthamine showed specific binding to AChE, whereas (+)-[11C]-galanthamine accumulated in brain tissue by non-specific binding. Thus, optically pure (-)-[11C]galanthamine could be a useful PET tracer for imaging cerebral AChE.

Probing Torpedo californica acetylcholinesterase catalytic Gorge with two novel bis-functional galanthamine derivatives

N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 ? showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough for the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 ? confirmed that a dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: a chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS). 2009 American Chemical Society.

Galanthamine derivatives, methods for their obtaining and use

This invention relates to new compounds that are galanthamine derivatives, to the methods of their obtaining and their use for prophylaxis and/or treatment of neurodegenerative diseases, senile dementia and Alzheimer's disease including. The new galanthamine derivatives obtained according to the invention combine two effects: inhibition of acetylcholinesterase and butyrylcholinesterase activity due to the galanthamine molecule and inhibition of γ-secretase activity characteristic to the peptide fragment.

Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors

A new series of galanthamine derivatives have been designed, synthesized and evaluated as acetylcholinesterase inhibitors. All of the new compounds prepared showed high AChE inhibitory activities, with compound 3e that has an N-hexyl-benzyl piperidine substituent on the nitrogen atom reaching the best inhibitory activity for AChE (IC50 = 5.62 nM). The docking study performed with AutoDock demonstrated that 3e was nicely accommodated by AChE.

Biomimetic synthesis of (±)-galanthamine and asymmetric synthesis of (-)-galanthamine using remote asymmetric induction

(±)-Galanthamine (1) was synthesized in excellent yield by applying PIFA-mediated oxidative phenol coupling of N-(4-hydroxy)phenethyl-N-(3′, 4′,5′-trialkoxy)benzyl formamide (15b) as a key step. Because of the symmetrical characteristics of the pyrogallol moiety in the substrate (15b), the phenol coupling resulted in a sole coupling product except for volatile components from the oxidizing agent. On the basis of the successful results of the above strategy, (-)-galanthamine (1) was synthesized by employing a novel remote asymmetric induction, where conformation of the seven-membered ring in the product of the phenol coupling was restricted by forming a fused-chiral imidazolidinone ring with D-phenylalanine on the benzylic C-N bond of the tri-O-alkylated gallyl amino moiety. The conformational restriction and successive debenzylation of the protected hydroxyl groups on the pyrogallol ring caused diastereoselective cyclization to yield a cyclic ether having the desired stereochemistry for the synthesis of (-)-1.

Total synthesis of (-)-galanthamine by remote asymmetric induction

A pivotal intramolecular Michael addition to form a fused 5,7,5 ring system and the skeleton of (-)-galanthamine (1) was completely controlled by a remote chiral imidazolidinone auxiliary derived from D-phenylalanine (see scheme). This total synthesis of the allylic alcohol 1 avoids the corresponding enone narwedine, a highly allergenic intermediate in previous syntheses of 1.

Synthesis and in vitro evaluation of galanthamine derivatives for examination of nicotinic acetylcholine receptor system

The synthesis and radioactive labeling of several galanthamine derivatives, 6-O-demethyl-6-O-fluoroethylgalanthamine, 10-N-demethyl-10-N-fluoroethylgalanthamine and N-methylgalanthaminium are reported. First in vitro evaluation were carried out to determine their properties as allosterically potentiating ligands of nicotinic receptors. N-methylgalanthaminium was found to be a promising candidate for further investigations.

Oxidative Intramolecular Phenolic Coupling Reaction Induced by a Hypervalent Iodine(III) Reagent: Leading to Galanthamine-Type Amaryllidaceae Alkaloids

By extending our oxidative phenol-coupling reactions using a hypervalent iodine(III) reagent, a versatile synthetic procedure for the galanthamine-type Amaryllidaceae alkaloids was accomplished. The first total synthesis of (±)-sanguinine and the total syntheses of (±)-galanthamine, (±)- narwedine, (±)-lycoramine, and (±)-norgalanthamine were also successfully carried out.