Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594133 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
Abstract
The structure-activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure-mutagenicity relationships for the released aromatic amine metabolites. Potent FAAH inhibitors were identified having heteroaryl amine leaving groups that were non-mutagenic in the Ames II assay.
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Authors
Mark S. Tichenor, John M. Keith, William M. Jones, Joan M. Pierce, Jeff Merit, Natalie Hawryluk, Mark Seierstad, James A. Palmer, Michael Webb, Mark J. Karbarz, Sandy J. Wilson, Michelle L. Wennerholm, Filip Woestenborghs, Dominiek Beerens, Lin Luo,