Synthesis and biological activity of peptidyl aldehyde urokinase inhibitors.
Solid- and solution-phase synthesis of peptidomimetic inhibitors of urokinase-type plasminogen activator based on the sequence dSerAlaArg-al are described. The biological activities of these unique inhibitors are reported herein. Carbonate prodrugs were prepared and tested as potential drug delivery systems.
Tamura
S Y
SY
Corvas International, Inc., Department of Medicinal Chemistry, San Diego, CA 92121, USA.
Weinhouse
M I
MI
Roberts
C A
CA
Goldman
E A
EA
Masukawa
K
K
Anderson
S M
SM
Cohen
C R
CR
Bradbury
A E
AE
Bernardino
V T
VT
Dixon
S A
SA
Ma
M G
MG
Nolan
T G
TG
Brunck
T K
TK
D000447:Aldehydes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D006207:Half-Life; D011355:Prodrugs / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D000447:Aldehydes; D004151:Dipeptides; D004791:Enzyme Inhibitors; D011355:Prodrugs; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator