Imidazopyridines as selective CYP3A4 inhibitors

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1611-4. doi: 10.1016/j.bmcl.2011.12.125. Epub 2012 Jan 4.


Cytochrome P450s are the major family of enzymes responsible for the oxidative metabolism of pharmaceuticals and xenobiotics. CYP3A4 and CYP3A5 have been shown to have overlapping substrate and inhibitor profiles and their inhibition has been demonstrated to be involved in numerous pharmacokinetic drug-drug interactions. Here we report the first highly selective CYP3A4 inhibitor optimized from an initial lead with ≈30-fold selectivity over CYP3A5 to yield a series of compounds with greater than 1000-fold selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors*
  • Enzyme Activation / drug effects
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Pyridines / chemistry*
  • Pyridines / pharmacology*


  • Cytochrome P-450 CYP3A Inhibitors
  • Imidazoles
  • Pyridines
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human