Discovery of 4-(5-(4-Chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfona mide (A-867744) as a Novel Positive Allosteric Modulator of the alpha 7 Nicotinic Acetylcholine Receptor

作者：Faghih Ramin^*; Gopalakrishnan Sujatha M; Gronlien Jens Halvard; Malysz John; Briggs Clark A; Wetterstrand Caroline; Ween Hilde; Curtis Michael P; Sarris Kathy A; Gfesser Gregory A; El Kouhen Rachid; Robb Holly M; Radek Richard J; Marsh Kennan C; Bunnelle William H; Gopalakrishnan Murali

来源：Journal of Medicinal Chemistry, 2009, 52(10): 3377-3384.

DOI：10.1021/jm9003818

The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha 7 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 0 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 0 nAChRs.

• 出版日期2009-5-28