title: Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.
abstract: Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease urokinase plasminogen activator (uPA) are described. Direct attachment of five-membered saturated or unsaturated rings improved inhibitor performance; substitution with sulfones further improved binding profiles. Combination of these substituents or of previously described NH-linked heteroaromatic rings with 6-phenyl amide substituents provided further enhancements to potency and selectivity.
authors.affiliation: Cancer Research, Global Pharmaceutical R & D, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6101, USA. mike.d.wendt@abbott.com
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wendt
authors.forename: Andrew
authors.initials: A
authors.lastname: Geyer
authors.forename: William J
authors.initials: WJ
authors.lastname: McClellan
authors.forename: Todd W
authors.initials: TW
authors.lastname: Rockway
authors.forename: Moshe
authors.initials: M
authors.lastname: Weitzberg
authors.forename: Xumiao
authors.initials: X
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Mantei
authors.forename: Kent
authors.initials: K
authors.lastname: Stewart
authors.forename: Vicki
authors.initials: V
authors.lastname: Nienaber
authors.forename: Vered
authors.initials: V
authors.lastname: Klinghofer
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Giranda
mesh_terms: D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D009281:Naphthalenes; D015842:Serine Proteinase Inhibitors; C031220:urokinase inhibitor; C018609:beta-naphthamidine; D014568:Urokinase-Type Plasminogen Activator