Inhibition of trypsin and urokinase by Cbz-amino(4-guanidinophenyl)methanephosphonate aromatic ester derivatives: the influence of the ester group on their biological activity.
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.
Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspiańskiego 27, 50-370 Wrocław, Poland.
Marcin
M
Sieńczyk
Józef
J
Oleksyszyn
D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D006146:Guanidines; D009943:Organophosphorus Compounds; D014361:Trypsin Inhibitors; D014357:Trypsin; D014568:Urokinase-Type Plasminogen Activator