Design, synthesis, and pharmacological evaluation of new farnesyl protein transferase inhibitors

J Med Chem. 2002 Jan 17;45(2):533-6. doi: 10.1021/jm010297r.

Abstract

New CA(1)A(2)X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heterocycles, taking into account the role of zinc and the metabolic instability of amino acids. The molecular docking of 8 in the active site of the enzyme and the pharmacological evaluation of the compounds are illustrative of a new class of FTIs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Cell Membrane Permeability
  • Cysteine / chemistry
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Methionine / chemistry
  • Mice
  • Models, Molecular
  • Molecular Mimicry
  • Peptides / chemistry*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Peptides
  • Thiazoles
  • Methionine
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • Cysteine