Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

Bin Ye; Yuo-Ling Chou; Rushad Karanjawala; Wheeseong Lee; Shou-Fu Lu; Kenneth J Shaw; Steven Jones; Dao Lentz; Amy Liang; Jih-Lie Tseng; Qingyu Wu; Zuchun Zhao

doi:10.1016/j.bmcl.2003.11.035

Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

Bioorg Med Chem Lett. 2004 Feb 9;14(3):761-5. doi: 10.1016/j.bmcl.2003.11.035.

Authors

Bin Ye¹, Yuo-Ling Chou, Rushad Karanjawala, Wheeseong Lee, Shou-Fu Lu, Kenneth J Shaw, Steven Jones, Dao Lentz, Amy Liang, Jih-Lie Tseng, Qingyu Wu, Zuchun Zhao

Affiliation

¹ Discovery Research, Berlex Biosciences, 2600 Hilltop Drive, PO Box 4099, Richmond, CA 94804-0099, USA. [email protected]

PMID: 14741285
DOI: 10.1016/j.bmcl.2003.11.035

Abstract

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.

MeSH terms

Animals
Blood Coagulation Tests
Drug Evaluation, Preclinical
Fibrinolysis / drug effects
Molecular Structure
Piperazines / chemical synthesis*
Piperazines / pharmacology*
Plasminogen Activator Inhibitor 1 / chemistry*
Plasminogen Activator Inhibitor 1 / metabolism
Rats
Structure-Activity Relationship

Substances

Piperazines
Plasminogen Activator Inhibitor 1