title: Phosphonates and phosphinates: novel leaving groups for benzisothiazolone inhibitors of human leukocyte elastase.
abstract: A novel class of alkyl and aryl phosphonate and phosphinate acid-based leaving groups has been developed for utilization in the synthesis of benzoisothiazolone (BIT) inhibitors of human leukocyte elastase (HLE). A number of BITs were synthesized with phosphonate and phosphinate acid-based leaving groups and were found to be potent inhibitors of HLE. Compound 3c with a diethyl phosphonate leaving group is the most potent inhibitor synthesized in this series with Ki* = 0.035 nM and ED50 = 2.0 mg/kg.
authors.affiliation: Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Sterling Winthrop Inc., Collegeville, Pennsylvania 19426, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Desai
authors.forename: J C
authors.initials: JC
authors.lastname: Court
authors.forename: E
authors.initials: E
authors.lastname: Ferguson
authors.forename: R J
authors.initials: RJ
authors.lastname: Gordon
authors.forename: D J
authors.initials: DJ
authors.lastname: Hlasta
authors.forename: R P
authors.initials: RP
authors.lastname: Dunlap
authors.forename: C A
authors.initials: CA
authors.lastname: Franke
mesh_terms: D006801:Humans; D019272:Leukocyte Elastase; D009943:Organophosphorus Compounds / Q000737:chemistry; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D009943:Organophosphorus Compounds; D013844:Thiazoles; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; C015699:1,2-benzisothiazoline-3-one