Alpha-7 nicotinic acetylcholine receptors (α7 nAChR)areimplicated in the modulation of many cognitive functions such as attention,working memory, and episodic memory. For this reason, α7 nAChRagonists represent promising therapeutic candidates for the treatmentof cognitive impairment associated with Alzheimerâs disease(AD) and schizophrenia. A medicinal chemistry effort, around our previouslyreported chemical series, permitted the discovery of a novel classof α7 nAChR agonists with improved selectivity, in particularagainst the α3 receptor subtype and better ADME profile. Theexploration of this series led to the identification of 5-(4-acetyl[1,4]diazepan-1-yl)pentanoicacid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25,SEN15924, WAY-361789), a novel, full agonist of the α7 nAChRthat was evaluated in vitroand in vivo. Compound 25proved to be potent and selective, andit demonstrated a fair pharmacokinetic profile accompanied by efficacyin rodent behavioral cognition models (novel object recognition andauditory sensory gating). [ABSTRACT FROM AUTHOR]