CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability

Bioorg Med Chem Lett. 2004 Dec 20;14(24):6017-21. doi: 10.1016/j.bmcl.2004.09.077.

Abstract

New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog).

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / pharmacokinetics*
  • Antioxidants / pharmacology*
  • Biological Availability
  • Dogs
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Humans
  • Molecular Conformation
  • Oxadiazoles / pharmacokinetics*
  • Oxadiazoles / pharmacology*
  • Oxidation-Reduction / drug effects
  • Palmitoyl Coenzyme A / antagonists & inhibitors*
  • Palmitoyl Coenzyme A / metabolism
  • Rats
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Fatty Acids
  • Oxadiazoles
  • para-trifluoro-methyl-5-phenyl-1,2,4-oxadiazole
  • Palmitoyl Coenzyme A