Synthesis of N,N'-disubstituted 3-aminobenzo[c] and [d]azepin-2-ones as potent and specific farnesyl transferase inhibitors

Bioorg Med Chem Lett. 2004 Feb 9;14(3):767-71. doi: 10.1016/j.bmcl.2003.11.013.

Abstract

A structure-activity study was performed by synthesis on N,N'-disubstitution of 3-aminobenzo[c] and [d]azepin-2-one 2 and 3 to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities.

Publication types

  • Comparative Study

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Azepines / chemical synthesis*
  • Azepines / pharmacology*
  • Caco-2 Cells / drug effects
  • Caco-2 Cells / enzymology
  • Cell Line, Transformed / transplantation
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Farnesyltranstransferase
  • Genes, ras
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Protein Conformation / drug effects
  • Rats
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Azepines
  • Enzyme Inhibitors
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase