1034473-63-6Relevant articles and documents
1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanesand6-(aryl) -6-[alkoxyalkyl]-3azabicyclo[3.1.0]hexanes: A new series of potent and selective triple reuptake inhibitors
Micheli, Fabrizio,Cavanni, Paolo,Arban, Roberto,Benedetti, Roberto,Bertani, Barbara,Bettati, Michela,Bettelini, Letizia,Bonanomi, Giorgio,Braggio, Simone,Checchia, Anna,Davalli, Silvia,Fabio, Romano Di,Fazzolari, Elettra,Fontana, Stefano,Marchioro, Carla,Minick, Doug,Negri, Michele,Oliosi, Beatrice,Read, Kevin D.,Sartori, Ilaria,Tedesco, Giovanna,Tarsi, Luca,Terreni, Silvia,Visentini, Filippo,Zocchi, Alessandro,Zonzin, Laura
experimental part, p. 2534 - 2551 (2010/08/22)
The discovery of new highly potent and selective triple reuptake inhibitors is reported. The new classes of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0] hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes are described together with detailed SAR. Appropriate decoration of the scaffolds was achieved with the help of a triple reuptake inhibitor pharmacophore model detailed here. Selected derivatives showed good oral bioavailability ( > 30%) and brain penetration (B/B > 4) in rats associated with high in vitro potency and selectivity at SERT, NET, and DAT. Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression.
AZABICYCLIC COMPOUNDS AS SEROTONINE, DOPAMINE AND NOREPINEPHRINE RE-UPTAKE INHIBITORS
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Page/Page column 50-51, (2008/12/06)
The present invention relates to novel compounds of Formula (I)' or pharmaceutically acceptable salts or a solvates thereof: wherein A is and K is a mono or bicyclic aryl group; R1 is selected from a group consisting of: halogen, C1-4alkyl and C1-4alkoxy, and such R1 may assume different meanings on the basis of p value; p is an integer from 0 to 5; R2 is a group P wherein P is and R3 is hydrogen, C1-4alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-3alkyl, haloC1-2alkyl or an optionally substituted phenyl group; X is oxygen, -NR8- or sulphur; n is 0 or 1; R7 is hydrogen or methyl; R4 is hydrogen or methyl; R5 is hydrogen or C1-4alkyl; R6 is hydrogen or C1-4alkyl; and R8 is hydrogen or C1-4alkyl; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as serotonin (5-HT), dopamine (DA) and norepinephrine (NE), re-uptake inhibitors.
