197807-71-9Relevant academic research and scientific papers
Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509
Hagishita, Sanji,Murakami, Yasushi,Seno, Kaoru,Kamata, Susumu,Haga, Nobuhiro,Konoike, Toshiro,Kanda, Yasuhiko,Kiyama, Ryuichi,Shiota, Takeshi,Ishihara, Yasunobu,Ishikawa, Michio,Shimamura, Mayumi,Abe, Koji,Yoshimura, Koji
, p. 1695 - 1714 (2007/10/03)
A novel series of CCK-B/gastrin receptor antagonists - ureidomethylcarbamoylphenylketone derivatives - were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and a tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.
