1,2,5-Oxadiazole analogues of leflunomide and related compounds

Eur J Med Chem. 2011 Jan;46(1):383-92. doi: 10.1016/j.ejmech.2010.10.029. Epub 2010 Nov 3.

Abstract

A new series of compounds, structurally related to leflunomide, based on the 1,2,5-oxadiazole ring system (furazan) has been synthesised, and their ability to undergo ring scission at physiological pH to afford the corresponding cyano-oximes has been analyzed. The latter, together with the respective nitro derivatives obtained by oxidation, have been characterised as weak inhibitors of rat dihydroorotate dehydrogenase (DHODH).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Isoxazoles / chemistry*
  • Isoxazoles / pharmacology
  • Leflunomide
  • Male
  • Models, Molecular
  • Oxadiazoles / chemistry*
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Protein Conformation
  • Rats
  • Rats, Wistar

Substances

  • Enzyme Inhibitors
  • Isoxazoles
  • Oxadiazoles
  • Oxidoreductases Acting on CH-CH Group Donors
  • dihydroorotate dehydrogenase
  • Leflunomide