Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors

Bioorg Med Chem Lett. 2001 Apr 9;11(7):915-8. doi: 10.1016/s0960-894x(01)00102-0.

Abstract

The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.

MeSH terms

  • Amidines / chemical synthesis*
  • Amidines / pharmacology*
  • Drug Design
  • Drug Evaluation, Preclinical
  • Plasminogen Activators / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / pharmacology*
  • Thiophenes / chemical synthesis
  • Thiophenes / pharmacology
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors*

Substances

  • Amidines
  • Thiazoles
  • Thiophenes
  • 2-aminothiazole
  • Plasminogen Activators
  • Urokinase-Type Plasminogen Activator