Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors

Bioorg Med Chem Lett. 2001 Jun 4;11(11):1379-82. doi: 10.1016/s0960-894x(01)00247-5.

Abstract

The serine protease urokinase plasminogen activator (uPA) is thought to play a central role in tumor metastasis and angiogenesis. Molecular modeling studies suggest that 5-thiomethylthiopheneamidine inhibits uPA by binding at the S1 pocket of the active site. Further structure based elaboration of this residue resulted in a novel class of potent and selective inhibitors of uPA.

MeSH terms

  • Antimetabolites / chemical synthesis
  • Antimetabolites / chemistry
  • Antimetabolites / pharmacology*
  • Binding Sites
  • Humans
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors*
  • Urokinase-Type Plasminogen Activator / physiology

Substances

  • Antimetabolites
  • Thiophenes
  • Urokinase-Type Plasminogen Activator