Non-thiol farnesyltransferase inhibitors: N-(4-acylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides

Bioorg Med Chem. 2003 Apr 3;11(7):1521-30. doi: 10.1016/s0968-0896(03)00064-6.

Abstract

We have designed the nitrophenylfurylacryl-substituted benzophenone 4f as a non-thiol farnesyltransferase inhibitor utilizing a novel aryl binding site of farnesyltransferase. Variation of the 2-acylamino substituent at the benzophenone core structure of our initial lead 4f yielded several non-thiol farnesyltransferase inhibitors with improved activity. These compounds display activity in the low nanomolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Amides / chemical synthesis*
  • Amides / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Farnesyltranstransferase
  • Furans / chemical synthesis*
  • Furans / pharmacology*
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nitro Compounds / chemical synthesis*
  • Nitro Compounds / pharmacology*
  • Protein Conformation
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship

Substances

  • Amides
  • Enzyme Inhibitors
  • Furans
  • Indicators and Reagents
  • Nitro Compounds
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase