title: Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines.
abstract: A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivity, and has been selected as a candidate for clinical evaluation.
authors.affiliation: Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK. christopher_barber@sandwich.pfizer.com
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Barber
authors.forename: Roger P
authors.initials: RP
authors.lastname: Dickinson
authors.forename: Paul V
authors.initials: PV
authors.lastname: Fish
mesh_terms: D006146:Guanidines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology; D011237:Predictive Value of Tests; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006146:Guanidines; D007546:Isoquinolines; D015842:Serine Proteinase Inhibitors; D014568:Urokinase-Type Plasminogen Activator