Design of novel N-(2,4-dioxo-1,2,3,4-tetrahydro-thieno[3,2-d]pyrimidin-7-yl)-guanidines as thymidine phosphorylase inhibitors, and flexible docking to a homology model

Bioorg Med Chem Lett. 2003 Jan 6;13(1):107-10. doi: 10.1016/s0960-894x(02)00828-4.

Abstract

A novel class of thymidine phosphorylase (TP) inhibitors has been designed based on analogy to the enzyme substrate as well as known inhibitors. Flexible docking studies, using a homology model of human TP, of the designed N-(2,4-dioxo-1,2,3,4-tetrahydro-thieno[3,2-d]pyrimidin-7-yl)-guanidines as well as their synthetic precursors provide insight into the observed experimental trends in binding affinity.

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Guanidines / chemistry*
  • Guanidines / pharmacology
  • Humans
  • Models, Molecular
  • Protein Binding
  • Structural Homology, Protein
  • Thymidine Phosphorylase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Guanidines
  • Thymidine Phosphorylase