1213899-46-7Relevant articles and documents
Dynamic power learning split preparation (S)- 6 - hydroxy - 1 - amino indane
-
Paragraph 0016-0019, (2017/08/25)
The invention relates to a method for preparing (S)-6-hydroxy-1-aminoindane through dynamic kinetic resolution. According to the method, 6-hydroxy-1-aminoindane serves as the raw materials, fold candida lipase serves as a resolution catalyst, L-(+)-O-acetyl-Alpha-hydroxyphenylacetic acid serves as an acyl donor, KT-02 serves as a racemization catalyst, reaction is performed in a hydrogen environment, and the 6-hydroxy-1-aminoindane can be converted into an acetyl compound of the (S)-6-hydroxy-1-aminoindane. After the compound is purified, acid hydrolysis and alkali free operation are performed on the compound under the protection of nitrogen, then the (S)-6-hydroxy-1-aminoindane is obtained, and an ee value of the final product is above 99 percent. According to the method, the advantages that operation is easy, the racemization catalyst is low in price and easy to obtain, the raw materials can be completely utilized and the optical purity of the product is high are achieved, and great instruction and application value is achieved in the production preparation of the (S)-6-hydroxy-1-aminoindane.
COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DEGENERATIVE DISORDERS
-
, (2015/05/26)
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.
Hydroxy-1-aminoindans and derivatives: Preparation, stability, and reactivity
Herzig, Yaacov,Lerman, Lena,Goldenberg, Willy,Lerner, David,Gottlieb, Hugo E.,Nudelman, Abraham
, p. 4130 - 4140 (2007/10/03)
The chemical stability and reactivity of hydroxy-1-aminoindans and their N-propargyl derivatives are strongly affected by the position of the OH group and its orientation relative to that of the amino moiety. Thus, the 4- and 6-OH regioisomers were found to be stable, while the 5-OH analogues were found to be inherently unstable as the free bases. The latter, having a para orientation between the OH and the amino moieties, could be isolated only as their hydrochloride salts. 7-Hydroxy-1-aminoindans and 7-hydroxy-1- propargylaminoindans represent an intermediate case; while sufficiently stable even as free bases, they exhibit, under certain experimental conditions, unexpected reactivity. The instability of the 5- and 7-hydroxy-aminoindans is attributed to their facile conversion to the corresponding, reactive quinone methide (QM) intermediates. The o-QM obtained from 7-hydroxy-aminoindans was successfully trapped with ethyl vinyl ether via a Diels-Alder reaction to give tricyclic acetals 32a,b.
Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease
Sterling, Jeffrey,Herzig, Yaacov,Goren, Tamar,Finkelstein, Nina,Lerner, David,Goldenberg, Willy,Miskolczi, Istvan,Molnar, Sandor,Rantal, Ferenc,Tamas, Tivadar,Toth, Gyorgy,Zagyva, Adela,Zekany, Andras,Lavian, Gila,Gross, Aviva,Friedman, Rachel,Razin, Michal,Huang, Wei,Krais, Boris,Chorev, Michael,Youdim, Moussa B.,Weinstock, Marta
, p. 5260 - 5279 (2007/10/03)
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
-
, (2008/06/13)
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
-
, (2008/06/13)
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
Novel Cerebroprotective Agents with Central Nervous System Stimulating Activity. 1. Synthesis and Pharmacology of 1-Amino-7-hydroxyindan Derivatives
Oshiro, Yasuo,Sakurai, Youji,Tanaka, Tatsuyoshi,Ueda, Hiraki,Kikuchi, Tetsuro,Tottori, Katura
, p. 2004 - 2013 (2007/10/02)
To developed a novel cerebroprotective agent with central nervous system (CNS) stimulating activity, a series of 1-amino-7-hydroxyindan derivatives was synthesized, and their effects on the survival time of mice under hypoxic conditions were tested.CNS-stimulating activity was also evaluated by examining the promotional effect on the recovery from cerebral concussion induced coma in mice.Several compounds prolonged the survival time of mice in hypoxic conditions at a dose of 30 mg/kg (sc or ip) and 100 mg/kg (po).They also exhibited the promotional effects on recovery from coma at a dose of 100 mg/kg po.The three most potent compounds in both tests, 1-amino-7-hydroxy-6-(1-methylpropyl)indan (20), 1-amino-7-hydroxy-4,6-dimethyl-2-phenylindan (30), and 1-amino-7-hydroxy,2,2,4,6-tetramethylindan (35) were selected for further investigations.Structure-activity relationships were also discussed.
