title: Design, synthesis and in vitro evaluation of potent, novel, small molecule inhibitors of plasminogen activator inhibitor-1.
abstract: We have synthesized and evaluated a series of tetramic acid-based and hydroxyquinolinone-based inhibitors of plasminogen activator inhibitor-1 (PAI-1). These studies resulted in the identification of several compounds which showed excellent potency against PAI-1. The design, synthesis and SAR of these compounds are described.
authors.affiliation: Xenova Limited, 957 Buckingham Avenue, Slough, Berks SL1 4NL, UK. adian_folkes@xenova.co.uk
authors.forename: Adrian
authors.initials: A
authors.lastname: Folkes
authors.forename: S David
authors.initials: SD
authors.lastname: Brown
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Canne
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Chan
authors.forename: Erin
authors.initials: E
authors.lastname: Engelhardt
authors.forename: Sergey
authors.initials: S
authors.lastname: Epshteyn
authors.forename: Richard
authors.initials: R
authors.lastname: Faint
authors.forename: Julian
authors.initials: J
authors.lastname: Golec
authors.forename: Art
authors.initials: A
authors.lastname: Hanel
authors.forename: Patrick
authors.initials: P
authors.lastname: Kearney
authors.forename: James W
authors.initials: JW
authors.lastname: Leahy
authors.forename: Morrison
authors.initials: M
authors.lastname: Mac
authors.forename: David
authors.initials: D
authors.lastname: Matthews
authors.forename: Michael P
authors.initials: MP
authors.lastname: Prisbylla
authors.forename: Jason
authors.initials: J
authors.lastname: Sanderson
authors.forename: Reyna J
authors.initials: RJ
authors.lastname: Simon
authors.forename: Zerom
authors.initials: Z
authors.lastname: Tesfai
authors.forename: Nigel
authors.initials: N
authors.lastname: Vicker
authors.forename: Shouming
authors.initials: S
authors.lastname: Wang
authors.forename: Robert R
authors.initials: RR
authors.lastname: Webb
authors.forename: Peter
authors.initials: P
authors.lastname: Charlton
mesh_terms: D002863:Chromogenic Compounds / Q000737:chemistry; D015195:Drug Design; D004341:Drug Evaluation; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D015394:Molecular Structure; D017395:Plasminogen Activator Inhibitor 1 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D002863:Chromogenic Compounds; D006912:Hydroxyquinolines; D017395:Plasminogen Activator Inhibitor 1; D011760:Pyrrolidinones; C009435:tetramic acid