209394-27-4

Usage

Uses

Used in Pharmaceutical Industry:
LADOSTIGIL is used as a therapeutic agent for the treatment of Alzheimer's disease. It serves as an inhibitor of monoamine oxidase (MAO-A and B), which helps in increasing the levels of neurotransmitters such as dopamine, norepinephrine, and serotonin. Additionally, it acts as an acetylcholinesterase inhibitor, enhancing the levels of acetylcholine, a crucial neurotransmitter involved in memory and learning processes. LADOSTIGIL also exhibits neuroprotective properties, safeguarding neurons from damage and degeneration.
Furthermore, LADOSTIGIL's dual inhibitory action and neuroprotective effects make it a potential candidate for the treatment of other neurological and cognitive disorders, although this would require further research and clinical trials to confirm its efficacy and safety in those contexts.

InChI:InChI=1/C16H20N2O2/c1-4-10-17-15-9-7-12-6-8-13(11-14(12)15)20-16(19)18(3)5-2/h1,6,8,11,15,17H,5,7,9-10H2,2-3H3/t15-/m1/s1

Upstream product

• 106-96-7 propargyl bromide 
• 2450-71-7 Propargylamine 
• 6165-75-9 propargyl benzenesulfonate 
• 909293-90-9 Ethylmethyl-carbamic acid 3-oxo-indan-5-yl ester 
• 62803-47-8 6-hydroxy-1-indanone 
• 936555-08-7 (R)-6-(N-Me,N-Et carbamoyl)-N-Boc 1 aminoindan 
• 209394-88-7 6-chloroacetoxy-N-trifluoroacetyl-(R)-1-aminoindan 
• 209394-87-6 6-chloroacetyl-N-trifluoroacetyl-(R)-1-aminoindan 
• 947674-87-5 N-[(R)-6-hydroxyindan-1-yl]carbamic acid tert-butyl ester 
• 155666-94-7 N-trifluoroacetyl-(R)-1-aminoindan 
• 169105-01-5 (R)-3-amino-2,3-dihydro-1H-inden-5-ol 
• 10277-74-4 (R)-1-Aminoindane 

Downstream Products

• 209394-46-7 ladostigil tartrate 
• 209394-46-7 ladostigil hemitartrate 

Relevant academic research and scientific papers

An efficient and promising method to prepare Ladostigil (TV3326) via asymmetric transfer hydrogenation catalyzed by Ru-Cs-DPEN in an HCOONa-H 2O-surfactant system

The enantiopure multi-functional anti Alzheimer's drug, Ladostigil (TV3326), was prepared by using asymmetric transfer hydrogenation (ATH) as a key step catalyzed by Ru-Cs-DPEN in an HCOONa-H2O-surfactant system. Good chemical yields with high enantiomeric excess were obtained and the catalyst could be recycled another five times.

Methods for isolating propargylated aminoindans

Disclosed is a process for isolating from a reaction mixture a salt of a mono-propargylated aminoindan having the structure wherein R1 is H, hydroxyl, alkoxy or wherein Y is O or S; R2 and R3 is each, independently, C1-8 alkyl, C6-12 aryl, C6-12 aralkyl, each optionally halo substituted, or hydrogen; where the reaction mixture further comprises a solvent, a primary aminoindan having the structure wherein R1 is defined as above, and a tertiary aminoindan having the structure the process comprising d) adding an acid to the reaction mixture; e) crystallizing the mono-propargylated aminoindan under conditions suitable for the formation of a crystalline salt of the mono-propargylated aminoindan; and f) recovering the crystalline salt of the mono-propargylated aminoindan, wherein the process is performed without addition of an organic solvent. Also disclosed are the crystalline diastereomeric salts produced by the process and pharmaceutical compositions containing the salts.

Process for the synthesis of enantiomeric indanylamine derivatives

A process for manufacturing (R)-propynylaminoindans, and alternatively, a process for manufacturing (S)-propynylaminoindans. The chiral propynylaminoindans include alkoxy or alkylcarbamates derivatives. The process comprises transfer or pressure hydrogenation in the presence of an optically active catalyst to reduce 1-indanones. The chiral product, either (S)- or (R)-indanols undergo nucleophilic substitution to produce the named product. In an additional aspect, the invention relates to novel intermediates and compounds, namely, substituted indanones, substituted (S)-indanols and substituted (R)-indanols.

Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease

Carbamate derivatives of N-propargylaminoindans (Series I) and N-propargylphenethylamines (Series II) were synthesized via multistep procedures from the corresponding hydroxy precursors. The respective rasagiline- and selegiline-related series were designed to combine inhibitory activities of both acetylcholine esterase (AChE) and monoamine oxidase (MAO) by virtue of their carbamoyl and propargylamine pharmacophores. Each compound was tested for these activities in vitro in order to find molecules with similar potencies against each enzyme. Compounds with such dual AChE and MAO inhibitory activities are expected to have potential for the treatment of Alzheimer's disease. The observed SAR also offers insight into the requirements of the active sites on these enzymes. A carbamate moiety was found to be essential for AChE inhibition, which was absent in the corresponding hydroxy precursors. The propargyl group caused 2-70-fold decrease in AChE inhibitory activity (depending on the position of the carbamoyl group) of Series I, but had little or no effect in Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were either equipotent to, or slightly (2- to 5-fold) less active as AChE inhibitors than, the corresponding compounds in Series II, while the 4-carbamyloxyphenyls were more potent. The presence of the carbamate moiety in 6- and 7-carbamyloxyphenyls of Series I, considerably decreased MAO-A and -B inhibitory activity, compared to that of the parent hydroxy analogues, while the opposite was true for Series II. Thus, the 6- and 7-carbamyloxyphenyls in Series I were 2-3 orders of magnitude weaker MAO inhibitors while the 4- carbamyloxyphenyls were equipotent with the corresponding compounds in Series II. In both series, N-methylation of the propargylamine enhanced the MAO (A and B equally) inhibitory activities and decreased the AChE inhibitory activity. Two candidates belonging to the indan and tetralin ring systems (24c, 27b) and one phenethylamine (53d) were identified as possible leads for further development based on the following criteria: (a) comparable AChE and MAO-B inhibitory activities, (b) good to moderate AChE inhibitory activity, and (c) lack of strong MAO-A selectivity. However, it is likely that these compounds will be metabolized to the corresponding phenols, with inhibitory activities against AChE and/or MAO-A or -B, different from those of the parent carbamates. Thus, the apparent enzyme inhibition will be a result of the combined inhibition of all of these individual metabolites. The results of our ongoing in vivo screening programs will be published elsewhere.