4-methyl-1,2,4-triazol-3-yl heterocycle as an alternative to the 1-methylimidazol-5-yl moiety in the farnesyltransferase inhibitor ZARNESTRA

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4361-4. doi: 10.1016/j.bmcl.2003.09.043.

Abstract

Replacement of the 1-methylimidazol-5-yl moiety in the farnesyltransferase inhibitor ZARNESTRA series by a 4-methyl-1,2,4-triazol-3-yl group gave us compounds with similar structure-activity relationship profiles showing that this triazole is potentially a good surrogate to imidazole for farnesyltransferase inhibition.

MeSH terms

  • Administration, Oral
  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Farnesyltranstransferase
  • Heterocyclic Compounds / administration & dosage
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Kinetics
  • Mice
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Quinolones / administration & dosage
  • Quinolones / chemical synthesis*
  • Quinolones / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Quinolones
  • Triazoles
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase
  • tipifarnib