High-throughput synthesis and optimization of thrombin inhibitors via urazole alpha-addition and Michael addition

Bioorg Med Chem Lett. 2003 Apr 17;13(8):1445-9. doi: 10.1016/s0960-894x(03)00155-0.

Abstract

A novel alpha-addition of propiolates to urazoles followed by Michael addition of a variety of nucleophiles has been developed for rapid production and optimization of peptidomimetic drug leads. This technology has produced a number of highly potent and selective inhibitors of the serine protease, thrombin.

MeSH terms

  • Alkynes / chemistry
  • Combinatorial Chemistry Techniques
  • Molecular Mimicry
  • Propionates / chemistry
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry

Substances

  • Alkynes
  • Propionates
  • Serine Proteinase Inhibitors
  • Triazoles
  • Thrombin
  • propiolic acid
  • urazole