Discovery of C-imidazole azaheptapyridine FPT inhibitors

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1134-6. doi: 10.1016/j.bmcl.2009.12.013. Epub 2009 Dec 6.

Abstract

The discovery of C-linked imidazole azaheptapyridine bridgehead FPT inhibitors is described. This novel class of compounds are sub nM FPT enzyme inhibitors with potent cellular inhibitory activities. This series also has reduced hERG activity versus previous N-linked imidazole series. X-ray of compound 10a bound to FTase revealed strong interaction between bridgehead imidazole 3N with catalytic zinc atom.

Publication types

  • Comparative Study

MeSH terms

  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Drug Discovery / methods*
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Farnesyltranstransferase / metabolism
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / metabolism
  • Imidazoles / pharmacology
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Pyridines / pharmacology

Substances

  • Imidazoles
  • Pyridines
  • Farnesyltranstransferase