Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1).
Compound 2 was identified by high throughput screening as a novel PAI-1 inhibitor. Systematic optimization of the A, B, and C segments of 2 resulted in the identification of a more potent compound 39 with good oral bioavailability. The synthesis and SAR data are presented in this report.
Ye
Bin
B
Discovery Research, Berlex Biosciences, 2600 Hilltop Drive, PO Box 4099, Richmond, CA 94804-0099, USA. bin_ye@berlex.com
Chou
Yuo-Ling
YL
Karanjawala
Rushad
R
Lee
Wheeseong
W
Lu
Shou-Fu
SF
Shaw
Kenneth J
KJ
Jones
Steven
S
Lentz
Dao
D
Liang
Amy
A
Tseng
Jih-Lie
JL
Wu
Qingyu
Q
Zhao
Zuchun
Z
D000818:Animals; D001780:Blood Coagulation Tests; D004353:Drug Evaluation, Preclinical; D005342:Fibrinolysis / Q000187:drug effects; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D010879:Piperazines; D017395:Plasminogen Activator Inhibitor 1