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

  • J Med Chem. 2012 Nov 26;55(22):10277-81. doi: 10.1021/jm3013568.
Riccardo Zanaletti  1 ,  Laura Bettinetti ,  Cristiana Castaldo ,  Ilaria Ceccarelli ,  Giuseppe Cocconcelli ,  Thomas A Comery ,  John Dunlop ,  Eva Genesio ,  Chiara Ghiron ,  Simon N Haydar ,  Flora Jow ,  Laura Maccari ,  Iolanda Micco ,  Arianna Nencini ,  Carmela Pratelli ,  Carla Scali ,  Elisa Turlizzi ,  Michela Valacchi
Affiliations
  • 1. Siena Biotech SpA, Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy. [email protected]
PMID: 23083093 DOI: 10.1021/jm3013568
Abstract

α7 Nicotinic acetylcholine receptors (α7 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 α7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.