Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors. II.
A series of phenoxyacetanilide derivatives was synthesized and their antagonist activities for human gastrin/cholecystokinin (CCK)-B and CCK-A receptors were evaluated. Among the compounds synthesized, 2-[3-[3-[N-[2-(N-methyl-N-phenylcarbamoylmethoxy)phenyl]-N-(N-meth yl-N- phenylcarbamoylmethyl)carbamoylmethyl]-ureido]phenyl]acetic acid (20i, DA-3934) exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A receptors. DA-3934 and its methyl ester derivative inhibited pentagastrin-induced gastric acid secretion in rats in a dose-dependent manner.
Takeda
Y
Y
New Product Research Loboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Kawagoe
K
K
Yokomizo
A
A
Yokomizo
Y
Y
Hosokami
T
T
Shimoto
Y
Y
Tabuchi
Y
Y
Ogihara
Y
Y
Otsubo
R
R
Honda
Y
Y
Yokohama
S
S
D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D010418:Pentagastrin / Q000037:antagonists & inhibitors; D010642:Phenoxyacetates / Q000138:chemical synthesis*; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000085:Acetates; D000897:Anti-Ulcer Agents; C113400:DA 3934; D005755:Gastrins; D010642:Phenoxyacetates; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D010418:Pentagastrin