Synthesis and Antiulcer Activity of Optical Isomers of 2-(4-Chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic Acid (Rebamipide)

The enantiomers of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid [(±)-1, rebamipide, OPC-12759], a new antiulcer agent that enhances mucosal resistance, were synthesized from optically active α-amino acid derivatives of 2(1H)-quinolinone. The key intermediates, α-amino acid derivatives, were prepared by asymmetric synthesis and optical resolution. The (+)-1 was about 1.7 times as potent as the (-)-isomer in antiulcer activity against ethanol-induced gastric ulcers.