Design, synthesis, and structure-activity relationships of substituted piperazinone-based transition state factor Xa inhibitors

Ting Su; Hua Yang; Deborah Volkots; John Woolfrey; Suiko Dam; Paul Wong; Uma Sinha; Robert M Scarborough; Bing-Yan Zhu

doi:10.1016/s0960-894x(02)01038-7

Design, synthesis, and structure-activity relationships of substituted piperazinone-based transition state factor Xa inhibitors

Bioorg Med Chem Lett. 2003 Feb 24;13(4):729-32. doi: 10.1016/s0960-894x(02)01038-7.

Authors

Ting Su¹, Hua Yang, Deborah Volkots, John Woolfrey, Suiko Dam, Paul Wong, Uma Sinha, Robert M Scarborough, Bing-Yan Zhu

Affiliation

¹ Department of Medicinal Chemistry, Millennium Pharmaceuticals Inc., 256 East Grand Avenue, South San Francisco, CA 94080, USA.

PMID: 12639568
DOI: 10.1016/s0960-894x(02)01038-7

Abstract

The structure-activity relationship of a novel series of substituted piperazinone-based factor Xa inhibitors is described. The most potent compound 34 displays IC(50) of 0.9 nM.

MeSH terms

Anticoagulants / chemical synthesis
Anticoagulants / chemistry
Binding Sites
Drug Design
Factor Xa Inhibitors*
Humans
Inhibitory Concentration 50
Models, Molecular
Molecular Conformation
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / pharmacology
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship
Thrombin / antagonists & inhibitors

Substances

Anticoagulants
Factor Xa Inhibitors
Piperazines
Serine Proteinase Inhibitors
Thrombin