title: Active site-directed thrombin inhibitors: alpha-hydroxyacyl-prolyl-arginals. New orally active stable analogs of D-Phe-Pro-Arg-H.
abstract: D-alpha-Hydroxyacyl-prolyl-arginals have been designed and synthesized as orally active stable analogs of D-Phe-Pro-Arg-H, the active site-directed peptidyl thrombin inhibitor prototype. Many of the new analogs possess high in vitro anticoagulant activity while having little effect on fibrinolysis. Compounds GYKI-66104 (2), -66131 (3) and -66132 (5) effectively delay the clotting time in rabbits ex vivo and prevent thrombus formation in various thrombosis models in rabbits and rats when applied in a single oral dose of 5 mg kg-1.
authors.affiliation: Institute for Drug Research, Budapest, Hungary.
authors.forename: S
authors.initials: S
authors.lastname: Bajusz
authors.forename: E
authors.initials: E
authors.lastname: Barabás
authors.forename: I
authors.initials: I
authors.lastname: Fauszt
authors.forename: A
authors.initials: A
authors.lastname: Fehér
authors.forename: G
authors.initials: G
authors.lastname: Horváth
authors.forename: A
authors.initials: A
authors.lastname: Juhász
authors.forename: A G
authors.initials: AG
authors.lastname: Szabó
authors.forename: E
authors.initials: E
authors.lastname: Széll
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D000991:Antithrombins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001777:Blood Coagulation / Q000187:drug effects; D015195:Drug Design; D005342:Fibrinolysis / Q000187:drug effects; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D007202:Indicators and Reagents; D009842:Oligopeptides; C077952:phenylalanyl-prolyl-arginine; D013917:Thrombin