Synthesis of 5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidine-N-cyanoguanidine derivatives as inhibitors of ras farnesyl protein transferase

Bioorg Med Chem Lett. 2002 Feb 25;12(4):601-5. doi: 10.1016/s0960-894x(01)00826-5.

Abstract

A series of novel N-cyanoguanidine tricyclic farnesyl protein transferase (FPT) inhibitors was prepared. Replacement of a piperidine amide-group with a N-cyanoguanidine functionality increased FPT activity. X-ray crystal structure determination of 42 complexed with FPT revealed differences in the interactions of the amide and N-cyanoguanidine groups with the protein.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Guanidines / chemical synthesis*
  • Guanidines / chemistry
  • Guanidines / pharmacology*
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Guanidines
  • Heterocyclic Compounds, 4 or More Rings
  • Piperidines
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • dicyandiamido