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.
Sieńczyk
Marcin
M
Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspiańskiego 27, 50-370 Wrocław, Poland.
Oleksyszyn
Józef
J
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