- Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders: structure-activity relationship.
Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders: structure-activity relationship.
Journal of medicinal chemistry (2004-04-02)
Stig Jönsson, Gunnar Andersson, Tomas Fex, Tomas Fristedt, Gunnar Hedlund, Karl Jansson, Lisbeth Abramo, Ingela Fritzson, Olga Pekarski, Anna Runström, Helena Sandin, Ingela Thuvesson, Anders Björk
PMID15056005
ABSTRACT
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).
MATERIALS