Synthesis and biological activity of peptidyl aldehyde urokinase inhibitors

S Y Tamura; M I Weinhouse; C A Roberts; E A Goldman; K Masukawa; S M Anderson; C R Cohen; A E Bradbury; V T Bernardino; S A Dixon; M G Ma; T G Nolan; T K Brunck

doi:10.1016/s0960-894x(00)00149-9

Synthesis and biological activity of peptidyl aldehyde urokinase inhibitors

Bioorg Med Chem Lett. 2000 May 1;10(9):983-7. doi: 10.1016/s0960-894x(00)00149-9.

Authors

S Y Tamura¹, M I Weinhouse, C A Roberts, E A Goldman, K Masukawa, S M Anderson, C R Cohen, A E Bradbury, V T Bernardino, S A Dixon, M G Ma, T G Nolan, T K Brunck

Affiliation

¹ Corvas International, Inc., Department of Medicinal Chemistry, San Diego, CA 92121, USA.

PMID: 10853674
DOI: 10.1016/s0960-894x(00)00149-9

Abstract

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.

MeSH terms

Aldehydes / chemical synthesis*
Aldehydes / pharmacokinetics
Aldehydes / pharmacology
Animals
Area Under Curve
Chromatography, High Pressure Liquid
Dipeptides / chemical synthesis*
Dipeptides / pharmacokinetics
Dipeptides / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology
Fibrinolysin / antagonists & inhibitors
Half-Life
Prodrugs / chemical synthesis
Prodrugs / pharmacokinetics
Prodrugs / pharmacology
Rats
Tissue Plasminogen Activator / antagonists & inhibitors
Urokinase-Type Plasminogen Activator / antagonists & inhibitors*

Substances

Aldehydes
Dipeptides
Enzyme Inhibitors
Prodrugs
Tissue Plasminogen Activator
Fibrinolysin
Urokinase-Type Plasminogen Activator