SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors

Bioorg Med Chem Lett. 2005 Nov 1;15(21):4854-7. doi: 10.1016/j.bmcl.2005.07.053.

Abstract

Novel DHODH inhibitors were developed based on a previously described series by introduction of heteroatoms into the cyclopentene ring and hydroxyl groups attached to it. Also, the hydrophobic biphenyl side chain was replaced with benzyloxy phenyl groups. Activities on human, rat, and mouse enzymes indicate a species specificity of these inhibitors.

MeSH terms

  • Amides
  • Animals
  • Cell Proliferation / drug effects*
  • Cyclopentanes / chemical synthesis*
  • Cyclopentanes / pharmacology
  • Dihydroorotate Oxidase / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Immunosuppressive Agents / chemical synthesis*
  • Immunosuppressive Agents / pharmacology
  • Inhibitory Concentration 50
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Mice
  • Rats
  • Species Specificity
  • Structure-Activity Relationship

Substances

  • Amides
  • Cyclopentanes
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • cyclopentenedicarboxylic acid
  • Dihydroorotate Oxidase