title: Novel bicyclic lactam inhibitors of thrombin: highly potent and selective inhibitors.
abstract: The potency and selectivity of a previous series of low molecular weight thrombin inhibitors were improved through modifications of the P1 and P3 residues. Introduction of diphenyl substituted sulfonamides in the P3 moiety led to highly efficacious compounds. By correctly selecting the combination of P1 and P3 residues, high levels of potency, selectivity and in vivo efficacy were obtained.
authors.affiliation: Shire BioChem., 275 Armand-Frappier Blvd., Laval, H7V 4A7, Québec, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: St-Denis
authors.forename: Sophie
authors.initials: S
authors.lastname: Lévesque
authors.forename: Benoit
authors.initials: B
authors.lastname: Bachand
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Edmunds
authors.forename: Lorraine
authors.initials: L
authors.lastname: Leblond
authors.forename: Patrice
authors.initials: P
authors.lastname: Préville
authors.forename: Micheline
authors.initials: M
authors.lastname: Tarazi
authors.forename: Peter D
authors.initials: PD
authors.lastname: Winocour
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
mesh_terms: D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000991:Antithrombins; D007769:Lactams