title: Novel nanomolar imidazo[4,5-b]pyridines as selective nitric oxide synthase (iNOS) inhibitors: SAR and structural insights.
abstract: Inducible arginine oxidation and subsequent NO production by correspondent synthase (iNOS) are important cellular answers to proinflammatory signals. Prolonged NO production has been proved in higher organisms to cause stroke or septic shock. Several classes of potent NOS inhibitors have been reported, most of them targeting the arginine binding site of the oxygenase domain. Here we disclose the SAR and the rational design of potent and selective iNOS inhibitors which may be useful as anti-inflammatory drugs.
authors.affiliation: Nycomed GmbH, Byk-Gulden-Str. 2, D-78467 Konstanz, Germany. ugraedler@hotmail.com
authors.forename: Ulrich
authors.initials: U
authors.lastname: Grädler
authors.forename: Thomas
authors.initials: T
authors.lastname: Fuchss
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Ulrich
authors.forename: Rainer
authors.initials: R
authors.lastname: Boer
authors.forename: Andreas
authors.initials: A
authors.lastname: Strub
authors.forename: Christian
authors.initials: C
authors.lastname: Hesslinger
authors.forename: Céline
authors.initials: C
authors.lastname: Anézo
authors.forename: Kay
authors.initials: K
authors.lastname: Diederichs
authors.forename: Andrea
authors.initials: A
authors.lastname: Zaliani
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; C029899:imidazole; D052247:Nitric Oxide Synthase Type II