Design, Synthesis and Antiinflammatory Activity of a New Indomethacin Ester. 2-[N-[3-{3-(Piperidinomethyl)phenoxy}propyl]carbamoylmethylthio]ethyl 1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate

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概要

• 論文の詳細を見る

• A novel indomethacin ester prodrug, 2-[N-[3-{3-(piperidinomethyl)phenoxy}propyl]carbamoylmethylthio]ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate (1) was prepared from a new histamine H_2-receptor antagonist, [N-[3-{3-(piperidinomethyl)phenoxy}propyl]-2-(2-hydroxyethylthio)acetamide (2) and indomethacin (3). The compound 1 was shown to be essentially similar to 3 in its antiinflammatory action and to almost completely inhibit carrageenin-induced hing-paw edema in the rat at a very high dose of 230 mg/kg (280 μmol/kg), which is comparable to that of 100 mg/kg (280 μmol/kg) of 3,without producing gastric lesions. On a molar basis, the acute gastric lesioning properties of 1 were near one-hundred times less than those of 3,resulting in over a twenty-fold improvement in the ratio of antiedema activity to ulcerogenicity. The effect of the co-administration of histamine H_2-receptor antagonists on antiedema activity and ulcerogenicity caused by 3 is also discussed.

• 社団法人日本薬学会の論文
• 1991-03-25

著者

• 植田 育男

  Institute Of Scientific And Industrial Reseach Osaka University

• 新井 平八郎

  Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.,

• 植田 育男

  The Institute of Scientific and Industrial Research, Osaka University

• 池田 眞一

  Central Research Laboratories Zeria Pharmaceutical Co. Ltd.

• 石井 克幸

  The Institute of Scientific and Industrial Research, Osaka University

• 人見 裕司

  Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.,

• 畠中 稔

  The Institute of Scientific and Industrial Research, Osaka University

• 新井 平八郎

  Central Research Laboratories Zeria Pharmaceutical Co. Ltd.

• 畠中 稔

  The Institute Of Scientific And Industrial Research Osaka University

• 石井 克幸

  The Institute Of Scientific And Industrial Research Osaka University

• 人見 裕司

  Central Research Laboratories Zeria Pharmaceutical Co. Ltd.

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