title: Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase.
abstract: The potency and selectivity of a series of 5-hetero-2-iminohexahydroazepines were examined as inhibitors of the three human NOS isoforms. The effect of ring substitution of the 5-carbon for a heteroatom is presented. Potencies (IC(50)'s) for these inhibitors are in the low micromolar range for hi-NOS with some examples exhibiting a 500x selectivity versus hec-NOS.
authors.affiliation: Pharmacia, 700 Chesterfield Parkway North, St. Louis, MO 63198, USA. alan.e.moormann@pharmacia.com
authors.forename: A E
authors.initials: AE
authors.lastname: Moormann
authors.forename: S
authors.initials: S
authors.lastname: Metz
authors.forename: M V
authors.initials: MV
authors.lastname: Toth
authors.forename: W M
authors.initials: WM
authors.lastname: Moore
authors.forename: G
authors.initials: G
authors.lastname: Jerome
authors.forename: C
authors.initials: C
authors.lastname: Kornmeier
authors.forename: P
authors.initials: P
authors.lastname: Manning
authors.forename: D W
authors.initials: DW
authors.lastname: Hansen
authors.forename: B S
authors.initials: BS
authors.lastname: Pitzele
authors.forename: R K
authors.initials: RK
authors.lastname: Webber
mesh_terms: D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II