N-[5-(5-Fluoropyridin-3-yl)-1H-pyrazol-3-yl]-4-piperidin-1-ylbutyramide (SEN78702, WYE-308775): A Medicinal Chemistry Effort toward an α7 Nicotinic Acetylcholine Receptor Agonist Preclinical Candidate

被引：15
|
作者：
Zanaletti, Riccardo [1 ]
Bettinetti, Laura [1 ]
Castaldo, Cristiana [1 ]
Ceccarelli, Ilaria [1 ]
Cocconcelli, Giuseppe [1 ]
Comery, Thomas A. [2 ]
Dunlop, John [2 ]
Genesio, Eva [1 ]
Ghiron, Chiara [1 ]
Haydar, Simon N. [2 ]
Jow, Flora [2 ]
Maccari, Laura [1 ]
Micco, Iolanda [1 ]
Nencini, Arianna [1 ]
Fratelli, Carmela [1 ]
Scali, Carla [1 ]
Turlizzi, Elisa [1 ]
Valacchi, Michela [1 ]
机构：
[1] Siena Biotech SpA, I-53100 Siena, Italy
[2] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 22期
关键词：
DISCOVERY; SCHIZOPHRENIA; RAT;
D O I：
10.1021/jm3013568
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment, associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort around previously reported compound 1 (SEN15924, WAY 361789) led to the identification of 12 (SEN78702, WYE-308775) a potent and selective full agonist of the alpha 7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.
引用
收藏
页码：10277 / 10281
页数：5
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