Design, synthesis and in vitro evaluation of potent, novel, small molecule inhibitors of plasminogen activator inhibitor-1.
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.
Folkes
Adrian
A
Xenova Limited, 957 Buckingham Avenue, Slough, Berks SL1 4NL, UK. adian_folkes@xenova.co.uk
Brown
S David
SD
Canne
Lynne E
LE
Chan
Jocelyn
J
Engelhardt
Erin
E
Epshteyn
Sergey
S
Faint
Richard
R
Golec
Julian
J
Hanel
Art
A
Kearney
Patrick
P
Leahy
James W
JW
Mac
Morrison
M
Matthews
David
D
Prisbylla
Michael P
MP
Sanderson
Jason
J
Simon
Reyna J
RJ
Tesfai
Zerom
Z
Vicker
Nigel
N
Wang
Shouming
S
Webb
Robert R
RR
Charlton
Peter
P
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
D002863:Chromogenic Compounds; D006912:Hydroxyquinolines; D017395:Plasminogen Activator Inhibitor 1; D011760:Pyrrolidinones; C009435:tetramic acid