50882-69-4Relevant academic research and scientific papers
Chiral aryloxyalkylamines: Selective 5-HT1B/1D activation and analgesic activity
Carocci, Alessia,Lentini, Giovanni,Catalano, Alessia,Cavalluzzi, Maria Maddalena,Bruno, Claudio,Muraglia, Marilena,Colabufo, Nicola Antonio,Galeotti, Nicoletta,Corbo, Filomena,Matucci, Rosanna,Ghelardini, Carla,Franchini, Carlo
scheme or table, p. 696 - 704 (2011/02/22)
A series of chiral 2,3-dichlorophenoxy and 1-naphthyloxy alkylamines were synthesized, and their binding affinities towards 5-HT1D and h5-HT1B receptors were evaluated. In the naphthyloxy series, the (R)-prolinol derivative was the most selective 5-HT1D ligand, while (S)-N-methyl-2-(1-naphthyloxy)propan-1-amine showed the highest selectivity for h5-HT1B. Both compounds performed as 5-HT1D agonists in the isolated guinea pig assay and showed higher analgesic activity than both sumatriptan and the achiral analogue 20b in the mouse hotplate test. Neither ligand displayed any affinity for nicotinic ACh receptors present in mouse brain membranes, thus indicating that their analgesic activity does not arise through interaction with these receptors.
Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake.
Bymaster,Beedle,Findlay,Gallagher,Krushinski,Mitchell,Robertson,Thompson,Wallace,Wong
, p. 4477 - 4480 (2007/10/03)
A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta) has proven to be effective in clinical trials for the treatment of depression.
2-(1-naphthyloxy)ethylamines with enhanced affinity for human 5-HT(1Dβ) (h5-HT(1B)) serotonin receptors
Ismaiel,Dukat,Law,Kamboj,Fan,Lee,Mazzocco,Buekschkens,Teitler,Pierson,Glennon
, p. 4415 - 4419 (2007/10/03)
Although the β-adrenergic antagonist propanolol (1) binds at rodent 5- HT(1B) serotonin receptors, it displays low affinity (K(i) > 10 000 nM) for its species homologue 5-HT(1DB) (i.e., h5-HT(1B)) receptors. The structure of propanolol was systematically modified in an attempt to enhance its affinity for the latter population of receptors. Removal of the alkyl hydroxyl group, shortening of the O-alkyl chain from three to two methylene groups, and variation of the terminal amine substituent resulted in compounds, such as N- monomethyl-2-(1-naphthyloxy)-ethylamine (11; K(i) = 26 nM), that display significantly higher h5-HT(1B) affinity than propanolol. Compound 11 was shown to bind equally well at human 5-HT(1Dα) (h5-HT(1D) receptors (K(i) = 34 nM) and was further demonstrated to possess h5-HT(1B) agonist character in an adenylate cyclase assay. It would appear that such (aryloxy)alkylamines may represent a novel class of 5-HT(1D) receptor agonists.
