Non-peptidic inhibitors of human neutrophil elastase: the design and synthesis of sulfonanilide-containing inhibitors.
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.
Imaki
K
K
Department of Medicinal Chemistry, Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Okada
T
T
Nakayama
Y
Y
Nagao
Y
Y
Kobayashi
K
K
Sakai
Y
Y
Mohri
T
T
Amino
T
T
Nakai
H
H
Kawamura
M
M
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
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