Biaryl analogues of teriflunomide as potent DHODH inhibitors

Bioorg Med Chem Lett. 2011 Dec 15;21(24):7268-72. doi: 10.1016/j.bmcl.2011.10.052. Epub 2011 Oct 20.

Abstract

The structure-activity relationships of a novel series of biaryl dihydroorotate dehydrogenase (DHODH) inhibitors related to teriflunomide are disclosed. These biaryl derivatives were the result of structure-based design and proved to be potent DHODH inhibitors which in addition showed good antiproliferative activities on peripheral blood mononuclear cells and good efficacies in vivo in the rat adjuvant-induced-arthritis model.

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Binding Sites
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry*
  • Biphenyl Compounds / therapeutic use
  • Computer Simulation
  • Crotonates / chemistry*
  • Dihydroorotate Dehydrogenase
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Hydroxybutyrates
  • Nitriles
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Protein Structure, Tertiary
  • Rats
  • Structure-Activity Relationship
  • Toluidines / chemistry*

Substances

  • Biphenyl Compounds
  • Crotonates
  • Dihydroorotate Dehydrogenase
  • Enzyme Inhibitors
  • Hydroxybutyrates
  • Nitriles
  • Toluidines
  • teriflunomide
  • Oxidoreductases Acting on CH-CH Group Donors

Associated data

  • PDB/3U2O