title: Oxyguanidines: application to non-peptidic phenyl-based thrombin inhibitors.
abstract: Although thrombin has been extensively researched with many examples of potent and selective inhibitors, the key characteristics of oral bioavailability and long half-life have been elusive. We report here a novel series non-peptidic phenyl-based, highly potent, highly selective and orally bioavailable thrombin inhibitors using oxyguanidines as guanidine-mimetics.
authors.affiliation: 3-Dimensional Pharmaceuticals, Inc., 665 Stockton Drive, Exton, PA 19341, USA. bruce.tomczuk@3dp.com
authors.forename: Bruce
authors.initials: B
authors.lastname: Tomczuk
authors.forename: Tianbao
authors.initials: T
authors.lastname: Lu
authors.forename: Richard M
authors.initials: RM
authors.lastname: Soll
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fedde
authors.forename: Aihua
authors.initials: A
authors.lastname: Wang
authors.forename: Larry
authors.initials: L
authors.lastname: Murphy
authors.forename: Carl
authors.initials: C
authors.lastname: Crysler
authors.forename: Malini
authors.initials: M
authors.lastname: Dasgupta
authors.forename: Stephen
authors.initials: S
authors.lastname: Eisennagel
authors.forename: John
authors.initials: J
authors.lastname: Spurlino
authors.forename: Roger
authors.initials: R
authors.lastname: Bone
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D018938:Caco-2 Cells; D004285:Dogs; D006146:Guanidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008861:Microsomes / Q000187:drug effects; D051381:Rats; D012697:Serine Endopeptidases / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D001555:Benzene Derivatives; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D013917:Thrombin