title: Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors.
abstract: The serine protease urokinase plasminogen activator (uPA) is thought to play a central role in tumor metastasis and angiogenesis. Molecular modeling studies suggest that 5-thiomethylthiopheneamidine inhibits uPA by binding at the S1 pocket of the active site. Further structure based elaboration of this residue resulted in a novel class of potent and selective inhibitors of uPA.
authors.affiliation: 3-Dimensional Pharmaceuticals Inc., 665 Stockton Drive, Exton, PA 19341, USA. nalin@3dp.com
authors.forename: N L
authors.initials: NL
authors.lastname: Subasinghe
authors.forename: C
authors.initials: C
authors.lastname: Illig
authors.forename: J
authors.initials: J
authors.lastname: Hoffman
authors.forename: M J
authors.initials: MJ
authors.lastname: Rudolph
authors.forename: K J
authors.initials: KJ
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Soll
authors.forename: T
authors.initials: T
authors.lastname: Randle
authors.forename: D
authors.initials: D
authors.lastname: Green
authors.forename: F
authors.initials: F
authors.lastname: Lewandowski
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Bone
authors.forename: J
authors.initials: J
authors.lastname: Spurlino
authors.forename: R
authors.initials: R
authors.lastname: DesJarlais
authors.forename: I
authors.initials: I
authors.lastname: Deckman
authors.forename: C J
authors.initials: CJ
authors.lastname: Molloy
authors.forename: C
authors.initials: C
authors.lastname: Manthey
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: C
authors.initials: C
authors.lastname: Sharp
authors.forename: D
authors.initials: D
authors.lastname: Maguire
authors.forename: C
authors.initials: C
authors.lastname: Crysler
authors.forename: B
authors.initials: B
authors.lastname: Grasberger
mesh_terms: D000963:Antimetabolites / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000963:Antimetabolites; D013876:Thiophenes; D014568:Urokinase-Type Plasminogen Activator