Inhibition of trypsin and urokinase by Cbz-amino(4-guanidinophenyl)methanephosphonate aromatic ester derivatives: the influence of the ester group on their biological activity

Marcin Sieńczyk; Józef Oleksyszyn

doi:10.1016/j.bmcl.2006.03.002

Inhibition of trypsin and urokinase by Cbz-amino(4-guanidinophenyl)methanephosphonate aromatic ester derivatives: the influence of the ester group on their biological activity

Bioorg Med Chem Lett. 2006 Jun 1;16(11):2886-90. doi: 10.1016/j.bmcl.2006.03.002. Epub 2006 Mar 20.

Authors

Marcin Sieńczyk¹, Józef Oleksyszyn

Affiliation

¹ Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspiańskiego 27, 50-370 Wrocław, Poland.

PMID: 16546384
DOI: 10.1016/j.bmcl.2006.03.002

Abstract

The urokinase plasminogen activator is a trypsin-like serine protease, important in tumor development. Here, we report the synthesis and biochemical evaluation of selective and potent diaryl esters of phosphonic-type inhibitors for urokinase. We have found that the substituted phenyl ester ring has a strong influence on the inhibitory activity of these compounds. This led to the most potent phosphonic inhibitor for uPA synthesized to date.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Guanidines / chemical synthesis*
Guanidines / chemistry
Guanidines / pharmacology
Molecular Structure
Organophosphorus Compounds / chemical synthesis*
Organophosphorus Compounds / chemistry
Organophosphorus Compounds / pharmacology
Structure-Activity Relationship
Trypsin / metabolism*
Trypsin Inhibitors / chemical synthesis*
Trypsin Inhibitors / chemistry
Trypsin Inhibitors / pharmacology*
Urokinase-Type Plasminogen Activator / antagonists & inhibitors*
Urokinase-Type Plasminogen Activator / metabolism*

Substances

Guanidines
Organophosphorus Compounds
Trypsin Inhibitors
Trypsin
Urokinase-Type Plasminogen Activator