Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors.
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.
Takeda
Y
Y
New Product Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Kawagoe
K
K
Yokomizo
A
A
Yokomizo
Y
Y
Hosokami
T
T
Ogihara
Y
Y
Honda
Y
Y
Yokohama
S
S
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000187:drug effects; D006224:Cricetinae; D005755:Gastrins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000081:Acetamides; C111699:DZ 3514; D005755:Gastrins; D010671:Phenylurea Compounds; D002766:Cholecystokinin