title: Design, synthesis and evaluation of polar head group containing 2-keto-oxazole inhibitors of FAAH.
abstract: 2-α-Keto oxazoles containing polar head groups in their C5-side chains were designed as fatty acid amide hydrolase (FAAH) inhibitors. Variation in the spacer length resulted in submicromolar α-keto-oxazole FAAH inhibitor (IC(50)=436 nM) presenting electrostatic stabilizing interactions between its polar head group contained in the C5-side chain and the hydrophilic pocket of the enzyme.
authors.affiliation: Department of Chemical Biology, Max-Planck Institute of Molecular Physiology, Otto-Hahn Strasse 11, D-44227 Dortmund, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Rusch
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahov
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Vetter
authors.forename: Matthias
authors.initials: M
authors.lastname: Lehr
authors.forename: Christian
authors.initials: C
authors.lastname: Hedberg
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D055672:Static Electricity; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D010080:Oxazoles; D000099252:Fatty Acid Amide Hydrolases