No 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).

This paper gives one approach of how to use experimental design in order to increase the yield for an organic synthesis. In this case the synthesis of 1-pyrrolemethane sulfonate was optimised. Two types of designs were used. First a series of screening experiments using fractional factonal design was applied.From these experiments a model was determined and used to locate the next experimental domain. The following experiments were planned as a Doehlert design in order to obtain a response surface model. "he optimum was estimated and confirmed experimentally. O 1996 by John Wiley & Son, Ltd.

This paper gives one approach of how to use experimental design in order to increase the yield for an organic synthesis. In this case the synthesis of 1-pyrrolemethane sulfonate was optimised. Two types of designs were used. First a series of screening experiments using fractional factonal design was applied.From these experiments a model was determined and used to locate the next experimental domain. The following experiments were planned as a Doehlert design in order to obtain a response surface model. "he optimum was estimated and confirmed experimentally. O 1996 by John Wiley & Son, Ltd.