874449-94-2Relevant academic research and scientific papers
Structure-activity relationship studies of SEN12333 analogues: Determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs
Beinat, Corinne,Reekie, Tristan,Banister, Samuel D.,O'Brien-Brown, James,Xie, Teresa,Olson, Thao T.,Xiao, Yingxian,Harvey, Andrew,O'Connor, Susan,Coles, Carolyn,Grishin, Anton,Kolesik, Peter,Tsanaktsidis, John,Kassiou, Michael
, p. 277 - 301 (2015/03/31)
Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described α7 agonist SEN12333 (8), have resulted in the identification of compound 45, a potent and selective agonist of the α7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8).
Novel alpha-7 nicotinic acetylcholine receptor agonists containing a urea moiety: Identification and characterization of the potent, selective, and orally efficacious agonist 1-[6-(4-Fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1- ylbutyl) Urea (SEN34625/WYE-103914)
Ghiron, Chiara,Haydar, Simon N.,Aschmies, Suzan,Bothmann, Hendrick,Castaldo, Cristiana,Cocconcelli, Giuseppe,Comery, Thomas A.,Di, Li,Dunlop, John,Lock, Tim,Kramer, Angela,Kowal, Dianne,Jow, Flora,Grauer, Steve,Harrison, Boyd,La Rosa, Salvatore,MacCari, Laura,Marquis, Karen L.,Micco, Iolanda,Nencini, Arianna,Quinn, Joanna,Robichaud, Albert J.,Roncarati, Renza,Scali, Carla,Terstappen, Georg C.,Turlizzi, Elisa,Valacchi, Michela,Varrone, Maurizio,Zanaletti, Riccardo,Zanelli, Ugo
scheme or table, p. 4379 - 4389 (2010/09/04)
Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment. We report a series of novel, potent small molecule agonists (4-18) of the α7 nAChR deriving from our continuing efforts in the areas of Alzheimer's disease and schizophrenia. One of the compounds of the series containing a urea moiety (16) was further shown to be a selective agonist of the α7 nAChR with excellent in vitro and in vivo profiles, brain penetration, and oral bioavailability and demonstrated in vivo efficacy in multiple behavioral cognition models. Structural modifications leading to the improved selectivity profile and the biological evaluation of this series of compounds are discussed.
SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist
Haydar, Simon N.,Ghiron, Chiara,Bettinetti, Laura,Bothmann, Hendrick,Comery, Thomas A.,Dunlop, John,La Rosa, Salvatore,Micco, Iolanda,Pollastrini, Martina,Quinn, Joanna,Roncarati, Renza,Scali, Carla,Valacchi, Michela,Varrone, Maurizio,Zanaletti, Riccardo
experimental part, p. 5247 - 5258 (2009/12/01)
Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment associated with a variety of disorders including Alzheimer's disease and schizophrenia. Alpha 7 nAChRs are expressed in brain regions associated with cognitive function, regulate cholinergic neurotransmission and have been shown to be down regulated in both schizophrenia and Alzheimer's disease. Herein we report a novel, potent small molecule agonist of the alpha 7 nAChR, SEN12333/WAY-317538. This compound is a selective agonist of the α7 nAChR with excellent in vitro and in vivo profiles, excellent brain penetration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioural cognition models. The SAR and biological evaluation of this series of compounds are discussed.
MODULATORS OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS AND THERAPEUTIC USES THEREOF
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Page/Page column 58, (2010/02/15)
The present invention relates to compounds with α7 nAChR agonistic activity, processes for their preparation, pharmaceutical compositions containing the same and the use thereof for the treatment of neurological, psychiatric, cognitive, immunological and inflammatory disorders.
