2. Academic Validation
  3. 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 alpha7 nicotinic acetylcholine receptor

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 alpha7 nicotinic acetylcholine receptor

  • J Med Chem. 2009 May 28;52(10):3377-84. doi: 10.1021/jm9003818.
Ramin Faghih 1,  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
Affiliations

Affiliation

  • 1 Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. ramin.faghih@abbott.com
PMID: 19419141 DOI: 10.1021/jm9003818
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.

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