Design and synthesis of oxadiazolidinediones as inhibitors of plasminogen activator inhibitor-1.
A novel series of PAI-1 inhibitors containing an oxadiazolidinedione moiety were identified by high through-put screening. Optimization of substituents by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described.
Gopalsamy
Ariamala
A
Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA. gopalsa@wyeth.com
Kincaid
Scott L
SL
Ellingboe
John W
JW
Groeling
Thomas M
TM
Antrilli
Thomas M
TM
Krishnamurthy
Girija
G
Aulabaugh
Ann
A
Friedrichs
Gregory S
GS
Crandall
David L
DL
D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007536:Isomerism; D008856:Microscopy, Fluorescence; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D023303:Oxazolidinones; D017395:Plasminogen Activator Inhibitor 1