title: Novel bicyclic lactam inhibitors of thrombin: potency and selectivity optimization through P1 residues.
abstract: Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the P1 residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vivo.
authors.affiliation: Shire BioChem Inc., 275 Armand-Frappier Blvd., Laval, H7V 4A7, Québec, Canada. slevesque@ca.shire.com
authors.forename: S
authors.initials: S
authors.lastname: Lévesque
authors.forename: Y
authors.initials: Y
authors.lastname: St-Denis
authors.forename: B
authors.initials: B
authors.lastname: Bachand
authors.forename: P
authors.initials: P
authors.lastname: Préville
authors.forename: L
authors.initials: L
authors.lastname: Leblond
authors.forename: P D
authors.initials: PD
authors.lastname: Winocour
authors.forename: J J
authors.initials: JJ
authors.lastname: Edmunds
authors.forename: J R
authors.initials: JR
authors.lastname: Rubin
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects; D066298:In Vitro Techniques; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000991:Antithrombins; D007769:Lactams; D013917:Thrombin