A new EP4 receptor agonist, KAG-308 was designed and synthesized efficiently by the route using one-step difluorination of Corey lactone derivative and the subsequent stereoselective Wittig reaction. It showed a high and selective affinity for human EP4 receptor. KAG-308 is orally available because of its high chemical and metabolical stability. Orally administered KAG-308 prevented the symptoms in the DSS-induced acute colitis model in mouse, and also demonstrated a therapeutic effects on relapse in the chronic model and promoted induction of remission. KAG-308, an orally available EP4 agonist, is a promising drug for induction and maintenance of remission in inflammatory bowel disease in clinical studies. The synthesis and pharmacological activities for the compounds will be described herein.

Discovery of KAG-308: A potent and orally available EP4 agonist for the treatment of inflammatory bowel disease

2019 Spring National Meeting

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