| Title : 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_2010_J.Med.Chem_53_4379 |
| Author(s) : Ghiron C , Haydar SN , Aschmies S , Bothmann H , Castaldo C , Cocconcelli G , Comery TA , Di L , Dunlop J , Lock T , Kramer A , Kowal D , Jow F , Grauer S , Harrison B , La Rosa S , Maccari L , Marquis KL , Micco I , Nencini A , Quinn J , Robichaud AJ , Roncarati R , Scali C , Terstappen GC , Turlizzi E , Valacchi M , Varrone M , Zanaletti R , Zanelli U |
| Ref : Journal of Medicinal Chemistry , 53 :4379 , 2010 |
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Abstract :
Alpha-7 nicotinic acetylcholine receptor (alpha7 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 alpha7 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 alpha7 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. |
| PubMedSearch : Ghiron_2010_J.Med.Chem_53_4379 |
| PubMedID: 20465311 |
Ghiron C, Haydar SN, Aschmies S, Bothmann H, Castaldo C, Cocconcelli G, Comery TA, Di L, Dunlop J, Lock T, Kramer A, Kowal D, Jow F, Grauer S, Harrison B, La Rosa S, Maccari L, Marquis KL, Micco I, Nencini A, Quinn J, Robichaud AJ, Roncarati R, Scali C, Terstappen GC, Turlizzi E, Valacchi M, Varrone M, Zanaletti R, Zanelli U (2010)
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)
Journal of Medicinal Chemistry
53 :4379
Ghiron C, Haydar SN, Aschmies S, Bothmann H, Castaldo C, Cocconcelli G, Comery TA, Di L, Dunlop J, Lock T, Kramer A, Kowal D, Jow F, Grauer S, Harrison B, La Rosa S, Maccari L, Marquis KL, Micco I, Nencini A, Quinn J, Robichaud AJ, Roncarati R, Scali C, Terstappen GC, Turlizzi E, Valacchi M, Varrone M, Zanaletti R, Zanelli U (2010)
Journal of Medicinal Chemistry
53 :4379