title: Design, synthesis and testing of amino-bicycloaryl based orally bioavailable thrombin inhibitors.
abstract: Replacement of the highly basic benzamidine moiety with moderate basic amino-bicycloaryl moieties in a series of thrombin inhibitors related to NAPAMP provided potent enzyme inhibition and significant improvements in membrane transport and oral bioavailability.
authors.affiliation: NV Organon, Research and Development, Oss, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: Rewinkel
authors.forename: H
authors.initials: H
authors.lastname: Lucas
authors.forename: M J
authors.initials: MJ
authors.lastname: Smit
authors.forename: A B
authors.initials: AB
authors.lastname: Noach
authors.forename: T G
authors.initials: TG
authors.lastname: van Dinther
authors.forename: A M
authors.initials: AM
authors.lastname: Rood
authors.forename: A J
authors.initials: AJ
authors.lastname: Jenneboer
authors.forename: C A
authors.initials: CA
authors.lastname: van Boeckel
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology; D000991:Antithrombins / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007546:Isoquinolines; D010880:Piperidines; D015842:Serine Proteinase Inhibitors; D013917:Thrombin