A Novel Histamine 2(H_2) Receptor Antagonist with Gastroprotective Activity. I. Synthesis and Pharmacological Evaluation of N-Phenoxypropylacetamide Derivatives with Thioether Function

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概要

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• In an attempt to develop new types of anti-ulcer agents, a series of N-(phenoxypropyl)acetamide derivatives with a thioether moiety and their sulfur-oxidized analogues were synthesized and evaluated for histamine H_2-receptor antagonistic activity, Ca antagonisitic activity and gastric anti-secretory activity in the lumen-perfussed rat. Selected compounds were also tested for gastroprotective activity, which was expected to be based on Ca antagonistic activity. Structure-activity relationships are discussed. As a thioether moiety, -CH_2-S(O)p-CH_2-Ar (Ar; phenyl or furyl) was found to be optimal for the above activities. Especially, N-[3-[(3-(piperidinomethyl) phenoxy]propyl]acetamide with a banzyl sulfinyl, benzylsulfonyl, furfurylsulfinyl or furfurylsulfonyl group showed potent gastroprotective activity upon oral administration in a rat model. These compounds are candidates for novel anti-ulcer drugs with gastric anti-secretory and gastroprotective activities. 2-Furfurylsulfinyl-N-[3-[(piperidinomethyl)phenoxy]propyl]-acetamide was the most potent among the compounds tested and was given the code designation FRG-8701.

• 公益社団法人日本薬学会の論文
• 1998-04-15

著者

• Sekine Akihiro

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Sekine Akihiro

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Osaka University

• Sekine Akihiro

  東邦大学 薬

• Sekine Y

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Sekine Yasuo

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• HIRAKAWA Nobuhiko

  Pharmaceuticals Research Laboratories, Fujirebio Inc.

• MATSUMOTO Hajime

  Pharmaceuticals Research Laboratories, Fujirebio Inc.

• YAMAURA Tetsuaki

  Pharmaceuticals Research Laboratories, Fujirebio Inc.

• KASHIWABA Noriaki

  Pharmaceuticals Research Laboratories, Fujirebio Inc.

• KUTSUMA Teruo

  Pharmaceuticals Research Laboratories, Fujirebio Inc.

• Kutsuma T

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Yamaura Tetsuaki

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Matsumoto H

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Sekine A

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Yamaura T

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Kashiwaba Noriaki

  Pharmaceuticals Research Laboratories Fujirebio Inc.

• Hirakawa Nobuhiko

  Pharmaceuticals Research Laboratories Fujirebio Inc.

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