title: Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders: structure-activity relationship.
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).
authors.affiliation: Active Biotech Research AB, Box 724, SE-220 07 Lund, Sweden. stig.jonsson@activebiotech.com
authors.forename: Stig
authors.initials: S
authors.lastname: Jönsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Andersson
authors.forename: Tomas
authors.initials: T
authors.lastname: Fex
authors.forename: Tomas
authors.initials: T
authors.lastname: Fristedt
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hedlund
authors.forename: Karl
authors.initials: K
authors.lastname: Jansson
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Abramo
authors.forename: Ingela
authors.initials: I
authors.lastname: Fritzson
authors.forename: Olga
authors.initials: O
authors.lastname: Pekarski
authors.forename: Anna
authors.initials: A
authors.lastname: Runström
authors.forename: Helena
authors.initials: H
authors.lastname: Sandin
authors.forename: Ingela
authors.initials: I
authors.lastname: Thuvesson
authors.forename: Anders
authors.initials: A
authors.lastname: Björk
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004285:Dogs; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D005260:Female; D006912:Hydroxyquinolines / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; D015363:Quinolones; C045282:roquinimex; C476223:laquinimod