title: Non-peptidic inhibitors of human neutrophil elastase: the design and synthesis of sulfonanilide-containing inhibitors.
abstract: A novel series of pivaloyloxy benzene derivatives has been identified as potent and selective human neutrophil elastase (HNE) inhibitors. Convergent syntheses were developed in order to identify the inhibitors which are intravenously effective in an animal model. A compound of particular interest is the sulfonanilide-containing analogues. Structure-activity relationships are discussed. Structural requirements for metabolic stabilization are also discussed.
authors.affiliation: Department of Medicinal Chemistry, Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imaki
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Nagao
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Mohri
authors.forename: T
authors.initials: T
authors.lastname: Amino
authors.forename: H
authors.initials: H
authors.lastname: Nakai
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008297:Male; D009504:Neutrophils / Q000201:enzymology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D000814:Aniline Compounds; D005998:Glycine; D019272:Leukocyte Elastase; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C105405:4-pivaloyloxy-N-phenylbenzenesulfonamide; D000096926:Benzenesulfonamides; C069195:sivelestat; C023650:aniline