Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders: structure-activity relationship

J Med Chem. 2004 Apr 8;47(8):2075-88. doi: 10.1021/jm031044w.


Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis*
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Autoimmune Diseases / drug therapy*
  • Dogs
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Female
  • Hydroxyquinolines / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / therapeutic use
  • Structure-Activity Relationship


  • Adjuvants, Immunologic
  • Hydroxyquinolines
  • Quinolones
  • roquinimex
  • laquinimod