Potent and selective bicyclic lactam inhibitors of thrombin. Part 4: Transition state inhibitors

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 eff...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2001-02, Vol.11 (3), p.287-290
Hauptverfasser:	BACHAND, Benoit, TARAZI, Micheline, ST-DENIS, Yves, EDMUNDS, Jeremy J, WINOCOUR, Peter D, LEBLOND, Lorraine, SIDDIQUI, M. Arshad
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Blood Coagulation Tests Blood. Blood coagulation. Reticuloendothelial system Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis Bridged Bicyclo Compounds, Heterocyclic - pharmacology Combinatorial Chemistry Techniques Crystallography, X-Ray Disease Models, Animal Fibrinolytic Agents - chemical synthesis Fibrinolytic Agents - pharmacology Lactams - chemical synthesis Lactams - pharmacology Medical sciences Models, Molecular Pharmacology. Drug treatments Rats Structure-Activity Relationship Thrombin - antagonists & inhibitors Thrombosis - drug therapy Trypsin Inhibitors - pharmacology
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Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(00)00636-3