Nicotinamide Derivatives as a New Class of Gastric (H^+/k^+)-ATPase Inhibitors. II. Synthesis and Structure-Activity Relationships of 2-[(2,4-Dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides

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概要

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• Members of a new series of 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides were synthesized and evaluated for their gastric antisecretory activity and the ability to inhibit cytochrome P450-dependent O-dealkylation of 7-ethoxycoumarin (7-EC) in rat liver microsomes. Several of the compounds synthesized exhibited potent inhibitory activities against both [^<14>C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats when administered intraduodenally; their inhibitory activities were equivalent to or superior to those of the parent compound [2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamide] and omeprazole. Among the compounds having potent antisecretory activity in vitro and in vivo, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,5-dimethyl-4-pyridinyl)pyridine-3-carboxamide and 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,6-dimethyl-4-pyridinyl)pyridine-3-carboxamide in particular showed lower inhibitory activity against the 7-EC deethylase than omeprazole. It seems probable that, unlike omeprazole, these compounds do not interact with a metabolism of other drugs in vivo. These compounds, therefore, are considered to be more promising candidate agents for treating acid-releated gastrointestinal disorders than the parent compound reported previously.

• 公益社団法人日本薬学会の論文
• 1997-06-15

著者

• Nakamura Katsuya

  Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.

• Nakamura K

  Department Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's Univ

• Nakamura Kazufumi

  Faculty Of Pharmaceutical Sciences Kyushu University

• Nakamura Katsuji

  Tsukuba Research Laboratories Eisai Co. Ltd.

• Tada Keiko

  Discovery Research Laboratories Dainippon Pharmaceutical Co. Ltd.

• Seto Yasuhiro

  Discovery Research Laboratories Dainippon Pharmaceutical Co. Ltd.

• TERAUCHI Hideo

  Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• TANITAME Akihiko

  Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• NAKAMURA Keiji

  Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• NISHIKAWA yoshinori

  Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.,

• Terauchi H

  Chemistry Research Laboratories Dainippon Pharmaceutical Co. Ltd.:pharmaceutical Research & Tech

• Tanitame A

  Discovery Research Laboratories Dainippon Pharmaceutical Co. Ltd.

• Nishikawa Y

  Dainippon Phaceutical Co. Ltd. Osaka Jpn

• Nishikawa Yoshinori

  Discovery Research Laboratories Dainippon Pharmaceutical Co. Ltd.

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