title: Synthesis and evaluation of non-basic inhibitors of urokinase-type plasminogen activator (uPA).
abstract: Recent drug discovery programs targeting urokinase plasminogen activator (uPA) have resulted in nonpeptidic inhibitors consisting of amidine or guanidine functional groups attached to aromatic or heteroaromatic scaffolds. There is a general problem of poor oral bioavailability of these charged inhibitors. In this paper, we report the synthesis and evaluation of a series of naphthamide and naphthalene sulfonamides as uPA inhibitors containing non-basic groups as substitute for amidine or guanidine groups.
authors.affiliation: Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Venkatraj
authors.forename: Jonas
authors.initials: J
authors.lastname: Messagie
authors.forename: Jurgen
authors.initials: J
authors.lastname: Joossens
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lambeir
authors.forename: Achiel
authors.initials: A
authors.lastname: Haemers
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001682:Biological Availability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D013449:Sulfonamides; D014568:Urokinase-Type Plasminogen Activator