title: Potent and selective bicyclic lactam inhibitors of thrombin: Part 2: P1 modifications.
abstract: The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors.
authors.affiliation: Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Plummer
authors.forename: K A
authors.initials: KA
authors.lastname: Berryman
authors.forename: C
authors.initials: C
authors.lastname: Cai
authors.forename: W L
authors.initials: WL
authors.lastname: Cody
authors.forename: J
authors.initials: J
authors.lastname: DiMaio
authors.forename: A M
authors.initials: AM
authors.lastname: Doherty
authors.forename: J J
authors.initials: JJ
authors.lastname: Edmunds
authors.forename: J X
authors.initials: JX
authors.lastname: He
authors.forename: D R
authors.initials: DR
authors.lastname: Holland
authors.forename: S
authors.initials: S
authors.lastname: Levesque
authors.forename: D R
authors.initials: DR
authors.lastname: Kent
authors.forename: L S
authors.initials: LS
authors.lastname: Narasimhan
authors.forename: J R
authors.initials: JR
authors.lastname: Rubin
authors.forename: S T
authors.initials: ST
authors.lastname: Rapundalo
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: A J
authors.initials: AJ
authors.lastname: Susser
authors.forename: Y
authors.initials: Y
authors.lastname: St-Denis
authors.forename: P D
authors.initials: PD
authors.lastname: Winocour
mesh_terms: D000818:Animals; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D005343:Fibrinolytic Agents; D007769:Lactams; D015842:Serine Proteinase Inhibitors; D013917:Thrombin