Discovery and Development of Laquinimod: An Immunomodulator for Treatment of Multiple Sclerosis

Starting with the lead compound roquinimex, a selection of 3-quinolinecarboxamide derivatives were synthesized and evaluated for the treatment of the autoimmune disease multiple sclerosis. Structure-activity relationships were established in animal studies and from these, laquinimod was chosen as the drug candidate due to its superior potency and toxicological profile as compared to roquinimex. However, the medicinal chemistry route used the hazardous reagents phosgene and sodium hydride and the route suffered from a tedious work up as well as unreliable quality. A safe and practical process initiating from readily available 2-amino-6-chlorobenzoic acid is described.