title: 4-amidinobenzylamine-based inhibitors of urokinase.
abstract: A series of 4-amidinobenzylamine-based peptidomimetic inhibitors of urokinase was synthesized. The most potent one, benzylsulfonyl-D-Ser-Ala-4-amidinobenzylamide 16, inhibits uPA with a K(i) of 7.7 nM but is less selective than 10 with a Gly as P2 residue. Hydroxyamidine and carbonate prodrugs were prepared, which are rapidly converted into the active inhibitors in rats after subcutaneous application.
authors.affiliation: Institut fur Biochemie und Biophysik, Universitat Jena, Philosophenweg 12, D-07743, Jena, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Künzel
authors.forename: Andrea
authors.initials: A
authors.lastname: Schweinitz
authors.forename: Siegmund
authors.initials: S
authors.lastname: Reissmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Stürzebecher
authors.forename: Torsten
authors.initials: T
authors.lastname: Steinmetzer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001596:Benzylamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D011355:Prodrugs; D014568:Urokinase-Type Plasminogen Activator