title: Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds.
abstract: Novel piperidine and piperazine derivatives have been designed and tested as inhibitors of LTA(4) hydrolase (LTA(4)H). Most potent compounds showed good potency in both enzymatic and functional human whole blood assay. Crystallography studies further confirmed observed structure-activity relationship and LTA(4)H binding mode for analogs from the piperidine series.
authors.affiliation: Medicinal Chemistry Department, deCODE Chemistry, Inc. 2501 Davey Road, Woodridge, IL 60517, United States.
authors.forename: Vincent
authors.initials: V
authors.lastname: Sandanayaka
authors.forename: Bjorn
authors.initials: B
authors.lastname: Mamat
authors.forename: Nikhil
authors.initials: N
authors.lastname: Bhagat
authors.forename: Louis
authors.initials: L
authors.lastname: Bedell
authors.forename: Gudrun
authors.initials: G
authors.lastname: Halldorsdottir
authors.forename: Heida
authors.initials: H
authors.lastname: Sigthorsdottir
authors.forename: Thorkell
authors.initials: T
authors.lastname: Andrésson
authors.forename: Alex
authors.initials: A
authors.lastname: Kiselyov
authors.forename: Mark
authors.initials: M
authors.lastname: Gurney
authors.forename: Jasbir
authors.initials: J
authors.lastname: Singh
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D010879:Piperazines; D010880:Piperidines; D000077489:Piperazine; C032727:piperidine; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase