title: Bicyclic pyridones as potent, efficacious and orally bioavailable thrombin inhibitors.
abstract: A new class of conformationally constrained thrombin inhibitors is described. These compounds contain a unique bicyclic pyridone scaffold which serves as a P3P2 dipeptide surrogate. The synthesis and antithrombotic activity of these inhibitors is reported.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. craig_coburn@merck.com
authors.forename: C A
authors.initials: CA
authors.lastname: Coburn
authors.forename: D M
authors.initials: DM
authors.lastname: Rush
authors.forename: P D
authors.initials: PD
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Homnick
authors.forename: E A
authors.initials: EA
authors.lastname: Lyle
authors.forename: S D
authors.initials: SD
authors.lastname: Lewis
authors.forename: B J
authors.initials: BJ
authors.lastname: Lucas
authors.forename: J M
authors.initials: JM
authors.lastname: Di Muzio-Mower
authors.forename: M
authors.initials: M
authors.lastname: Juliano
authors.forename: J A
authors.initials: JA
authors.lastname: Krueger
authors.forename: K
authors.initials: K
authors.lastname: Vastag
authors.forename: I W
authors.initials: IW
authors.lastname: Chen
authors.forename: J P
authors.initials: JP
authors.lastname: Vacca
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000494:pharmacology*; D000631:Aminopyridines / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001682:Biological Availability; D004151:Dipeptides / Q000737:chemistry; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D018716:Molecular Mimicry; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D000081:Acetamides; D000631:Aminopyridines; D000925:Anticoagulants; D004151:Dipeptides; D011728:Pyridones; D013917:Thrombin