215362-46-2Relevant articles and documents
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.
Structure activity relationship of homochiral 7-substituted 1- Aminoindans as 5-HT(1A) receptor ligands
Landsiedel-Maier, Dorothea,Frahm, August Wilhelm
, p. 59 - 71 (2007/10/03)
A series of homochiral 7-substituted 1-aminoindans was prepared by means of asymmetric reductive amination from racemic 7-substituted 1-indanones via E-imines and E-imine/enamine mixtures, respectively, and subjected to 5- hydroxytryptamine (5-HT) receptor subtype binding studies. The ee's of the title compounds were determined by HPLC of the corresponding Mosher's amides and range from 96 to 99.9%. The absolute configuration was elucidated by means of correlation CD spectroscopy. On the basis of the pK(I) values obtained from various test systems, structure activity relationships have been established with respect to the absolute configuration, degree of N- alkylation, and the type of 7-substituents. The tested 1-aminoindans show the highest affinity to the 5-HT(1A) receptor, with decreasing magnitude for the 5-HT(2A), 5-HT(1D), and 5-HT(2C) receptors. The highest affinities for the 5- HT(1A) receptor were observed for the R-(-)-7-propoxy-1-(di-n-propylamino)in- dan hydrochloride (R-(-)-30), S,S'-(+)-7-benzylamido-1-(1- phenylethylamino)indan hydrochloride [S,S'-(+)-19] and R-(-)-7-methoxyl-1- (di-n-propylamino)indan hydrogenembonate (R-(-)-29) with pK(I) = 7.07 ± 0.19, 6.40 ± 0.09, and 6.22 ± 0.10, respectively, in comparison to 8-OH- DPAT with pK(I) = 8.70 ± 0.30. Nearly all other compounds showed low affinity at all 5-HT receptors tested. The three above mentioned ligands were tested on HeLa cells (cell line HA6) expressing recombinant human 5-HT(1A) receptors for their effects on forskolin-stimulated cAMP accumulation in intact cells. Both the di-n-propylamino substituent bearing R-(-)-30 and R- (-)-29 acted as efficacious agonists with a pEC50 value of 5.89 ± 0.20 for R-(-)-30 compared to 5-HT with a pEC50 value of 8.06 ± 0.14. S,S'-(+)-19 with the 1-phenylethylamino substituent was devoid of intrinsic activity up to the highest tested concentration (10 μM).
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.
