Synthesis of Phenoxyacetic Acid Derivatives as Highly Potent Antagonists of Gastrin/Cholecystokinin-B Receptors

Abstract

A novel series of phenoxyacetic acid derivatives was synthesized based on considerations of the three-dimensional structural similarity of YM022 and RP72540. The gastrin/cholecystokinin (CCK)-B and CCK-A receptor antagonist activities of these compounds were evaluated by investigation of their affinities for human gastrin/CCK-B receptors and human CCK-A receptors, respectively. It was found that N-methyl-N-phenyl-2-[2-[N-(N-methyl-N-phenyl-carbamoylmethyl)-N-[2-[3-(3-methylphenyl)ureido]acetyl]amino]phenoxy]acetamide (20k, DZ-3514) exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A receptors.