title: Retro-binding thrombin active site inhibitors: identification of an orally active inhibitor of thrombin catalytic activity.
abstract: A series of retro-binding inhibitors of human alpha-thrombin was prepared to elucidate structure-activity relationships (SAR) and optimize in vivo performance. Compounds 9 and 11, orally active inhibitors of thrombin catalytic activity, were identified to be efficacious in a thrombin-induced lethality model in mice.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. iwanowie@bms.com
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Iwanowicz
authors.forename: S David
authors.initials: SD
authors.lastname: Kimball
authors.forename: James
authors.initials: J
authors.lastname: Lin
authors.forename: Wan
authors.initials: W
authors.lastname: Lau
authors.forename: W-C
authors.initials: WC
authors.lastname: Han
authors.forename: Tammy C
authors.initials: TC
authors.lastname: Wang
authors.forename: Daniel G M
authors.initials: DG
authors.lastname: Roberts
authors.forename: W A
authors.initials: WA
authors.lastname: Schumacher
authors.forename: Martin L
authors.initials: ML
authors.lastname: Ogletree
authors.forename: Steven M
authors.initials: SM
authors.lastname: Seiler
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002384:Catalysis; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity
chemical_list: C092032:BMS 183507; C471987:GYKI-14776; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D013917:Thrombin