155666-94-7

Usage

Uses

Used in Pharmaceutical Industry:
N-trifluoroacetyl-(R)-1-aminoindan is used as an intermediate in the synthesis of (3R)-2,3-Dihydro-3-(2-propyn-1-ylamino)-1H-inden-1-one (D449765). N-trifluoroacetyl-(R)-1-aminoindan is a vital building block in the preparation of Rasagiline (R126000), a selective irreversible MAO-B inhibitor. Rasagiline is employed as an Antiparkinsonian agent, helping to alleviate the symptoms of Parkinson's disease by targeting the monoamine oxidase B enzyme, which is involved in the breakdown of dopamine in the brain.

Upstream product

• 10277-74-4 (R)-1-Aminoindane 
• 407-25-0 trifluoroacetic anhydride 
• 10305-73-4 (R)-2,3-dihydro-1H-inden-1-amine hydrochloride 
• 169105-02-6 N-[(1R)-2,3-dihydro-1H-inden-1-yl]acetamide 
• 83-33-0 inden-1-one 

Downstream Products

• 161735-79-1 rasagiline mesylate 
• 136236-51-6 rasagiline 
• 209394-27-4 ladostigil 
• 947674-87-5 N-[(R)-6-hydroxyindan-1-yl]carbamic acid tert-butyl ester 
• 169105-01-5 (R)-3-amino-2,3-dihydro-1H-inden-5-ol 

Relevant academic research and scientific papers

Asymmetric Full Saturation of Vinylarenes with Cooperative Homogeneous and Heterogeneous Rhodium Catalysis

Homogeneous and heterogeneous catalyzed reactions can seldom operate synergistically under the same conditions. Here we communicate the use of a single rhodium precursor that acts in both the homogeneous and heterogeneous phases for the asymmetric full saturation of vinylarenes that, to date, constitute an unmet bottleneck in the field. A simple asymmetric hydrogenation of a styrenic olefin, enabled by a ligand accelerated effect, accounted for the facial selectivity in the consecutive arene hydrogenation. Tuning the ratio between the phosphine ligand and the rhodium precursor controlled the formation of homogeneous and heterogeneous catalytic species that operate without interference from each other. The system is flexible in terms of both the chiral ligand and the nature of the external olefin. We anticipate that our findings will promote the development of asymmetric arene hydrogenations.

COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND USE THEREOF

The invention generally relates to compounds of formula (I) with neural protective effect, and preparation and uses thereof. The compounds have multiple mechanisms or functions, for example, inhibition of monoamine oxidase and cholinesterase, scavenging of free radicals, and protection of cells such as nerve cells. The compounds can be used for manufacture of medicaments of cell protection, for prevention and/or treatment of monoamine oxidase, cholinesterase and free radicals related diseases, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and stroke, and free-radical related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DEGENERATIVE DISORDERS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I; and methods for treating or preventing neurological degenerative disorders, may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of Alzheimer's disease, Lewy body disease, Huntington's disease, Amyotrophic lateral sclerosis (ALS) and Parkinson's disease.

COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND USE THEREOF

The invention generally relates to compounds of formula (I) with neural protective effect, and preparation and uses thereof. The compounds have multiple mechanisms or functions, for example, inhibition of monoamine oxidase and cholinesterase, scavenging of free radicals, and protection of cells such as nerve cells. The compounds can be used for manufacture of medicaments of cell protection, for prevention and/or treatment of monoamine oxidase, cholinesterase and free radicals related diseases, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and stroke, and free-radical related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.

NEW METHOD FOR THE SYNTHESIS OF RASAGILINE

We have developed a new method for the synthesis of Rasagiline (Formula 1) based on the alkylation of trifluoroacetyl protected aminoindan. This protection enabled us to carry out an alkylation of aminoindan with a high yield and purity under very mild conditions with a wide range of reaction conditions and reagent selection. Considering the ease, purity and high yields of introducing and removal of the trifluoroacetyl group, this approach is a highly practical and economical way for the synthesis of rasagiline or its pharmaceutically acceptable salts.

A NEW METHOD FOR THE SYNTHESIS OF RASAGILINE

We have developed a new method for the synthesis of Rasagiline (Formula 1) based on the alkylation of trifluoroacetyl protected aminoindan. This protection enabled us to carry out an alkylation of aminoindan with a high yield and purity under very mild conditions with a wide range of reaction conditions and reagent selection. Considering the ease, purity and high yields of introducing and removal of the trifluoroacetyl group, this approach is a highly practical and economical way for the synthesis of rasagiline or its pharmaceutically acceptable salts.

3-KETO-N-PROPARGYL-1-AMINOINDAN

The subject invention provides a pharmaceutical composition containing N-propargyl-1(R)-aminoindan or a pharmaceutically acceptable salt thereof, and a compound of 3-keto-N-propargyl-1-aminoindan or a salt thereof.

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.

Aminoindan derivatives

This invention is directed to compounds of the following formula wherein when a is O, b is 1 or 2; when a is 1, b is 1, m is from 0-3 X is O or S, Y is halogeno, R1is hydrogen C1-4alkyl, R2is hydrogen, C1-4alkyl, or optionally substituted propargyl and R3and R4are each independently hydrogen, C1-8alkyl, C6-12aryl, C6-12aralkyl each optionally substituted. This invention is also directed to the use of these compounds for treating depression, Attention Deficit Disorder (ADC), Attention Deficit and Hyperactivity Disorder (ADHD), Tourette's Syndrome, Alzheimer's Disease and other dementia's such as senile dementia, dementia of the Parkinson's type, vascular dementia and Lewy body dementia. This invention is further directed to a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

Method for preparing optically active 1-aminoindan derivatives

Novel derivatives of 1-aminoindan and their salts are described. Optically active 1-aminoindan derivatives are prepared by reacting a N-benzyl analog of the desired compound with an enantiomer of mandelic acid. Parkinson's disease, dementia, epilepsy, con