Novel inhibitors of plasminogen activator inhibitor-1: development of new templates from diketopiperazines

Shouming Wang; Julian Golec; Warren Miller; Sandra Milutinovic; Adrian Folkes; Susannah Williams; Teresa Brooks; Kevin Hardman; Peter Charlton; Stephen Wren; John Spencer

doi:10.1016/s0960-894x(02)00389-x

Novel inhibitors of plasminogen activator inhibitor-1: development of new templates from diketopiperazines

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2367-70. doi: 10.1016/s0960-894x(02)00389-x.

Authors

Shouming Wang¹, Julian Golec, Warren Miller, Sandra Milutinovic, Adrian Folkes, Susannah Williams, Teresa Brooks, Kevin Hardman, Peter Charlton, Stephen Wren, John Spencer

Affiliation

¹ Department of Medicinal Chemistry, Xenova Ltd., Slough, Berkshire, UK. [email protected]

PMID: 12161135
DOI: 10.1016/s0960-894x(02)00389-x

Abstract

Several isoquinoline-based templates were identified from the studies of the conformational effects of the diketopiperazine structures for PAI-1 inhibition. Moderate to good activity was retained with the elimination of unattractive characteristics in the diketopiperazine template.

MeSH terms

Diketopiperazines
Humans
Inhibitory Concentration 50
Piperazines / chemical synthesis*
Piperazines / pharmacology
Plasminogen Activator Inhibitor 1 / chemistry*
Protein Binding
Structure-Activity Relationship

Substances

Diketopiperazines
Piperazines
Plasminogen Activator Inhibitor 1