title: Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: transition state inhibitors.
abstract: Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model.
authors.affiliation: BioChem Pharma Inc., Laval, Québec, Canada. bachandb@biochempharma.com
authors.forename: B
authors.initials: B
authors.lastname: Bachand
authors.forename: M
authors.initials: M
authors.lastname: Tarazi
authors.forename: Y
authors.initials: Y
authors.lastname: St-Denis
authors.forename: J J
authors.initials: JJ
authors.lastname: Edmunds
authors.forename: P D
authors.initials: PD
authors.lastname: Winocour
authors.forename: L
authors.initials: L
authors.lastname: Leblond
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D001780:Blood Coagulation Tests; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D008958:Models, Molecular; D051381:Rats; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000188:drug therapy; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005343:Fibrinolytic Agents; D007769:Lactams; D014361:Trypsin Inhibitors; D013917:Thrombin