Discovery of 4-(5-(4-Chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a Novel Positive Allosteric Modulator of the α7 Nicotinic Acetylcholine Receptor
Year: 2009
Type: article
Abstract: The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha7 nAChRs is described. Optimization of this series led to the identification of 19 (A-867744), a novel type II PAM with good potency and selectivity. Compound 19 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate alpha7 nAChRs. In a rodent model of sensory gating, 19 normalized gating deficits. These results suggest that 19 represents a novel class of molecules capable of allosteric modulation of the alpha7 nAChRs.
Source: Journal of Medicinal Chemistry
DOI: 10.1021/jm9003818
Authors: Ramin Faghih, Sujatha M. Gopalakrishnan, Jens Halvard Gronlien, John Malysz, Clark A. Briggs, Caroline Wetterstrand, Hilde Ween, Michael P. Curtis, Kathy A. Sarris, Gregory A. Gfesser, Rachid El-Kouhen, Holly M. Robb, Richard J. Radek, Kennan C. Marsh, William H. Bunnelle, Murali Gopalakrishnan
Institution: Abbott (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1982912816