2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. III. Synthesis of Metabolites and Metabolism of 2-(3-Pyridyl)thiazolidine-4-carboxamides YM461 and YM264 as Platelet-Activating Factor (PAF) Receptor Antagonists

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概要

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• The metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 was investigated, and their metabolites were compared with separately synthesized materials by measuring ^1H-NMR spectra, mass spectra, and HPLC retention times, and evaluated for platelet activating factor (PAF) antagonistic activity. YM461 was metabolized by two different metabolic pathways (cleavage of the thiazolidine ring and oxidation of the benzyl position), whereas YM264 was metabolized by three metabolic pathways. The minor metabolite M7 from YM264 possessed potent PAF antagonistic activity, as strong as YM264 and this existed as an active metabolite. From pharmacokinetics studies, YM264 was almost completely absorbed from the gastrointestinal tract, but readily metabolized in rats. In dogs, pharmacokinetic parameters of YM264 were significantly improved compared to those in rats, and YM264 tended to show better pharmacokinetics than YM461 due to an extension of the half-life period.

• 公益社団法人日本薬学会の論文
• 1999-02-15

著者

• 斎藤 徹

  Faculty Of Pharmaceutical Sciences Kanazawa University

• SUZUKI Takeshi

  Institute for Solid State Physics, University of Tokyo

• Suzuki T

  Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.

• Hara Hideaki

  Research And Development Center Santen Pharmaceutical Co. Ltd.

• MATSUMOTO Hisao

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• 鈴木 徳治

  千葉大 薬

• Suzuki T

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Takeuchi M

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Takeuchi Makoto

  Chemistry Research Laboratories Astellas Pharmaceutical Inc.

• TAKEUCHI Makoto

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• Takeuchi M

  Chemistry Research Laboratories Astellas Pharmaceutical Inc.

• Saito T

  Research And Development Headquarters Hokurikit Seiyaku Co. Ltd.

• Saito Takako

  Research And Development Laboratories Maruho Co. Ltd.

• YAMADA Tatsuhiko

  Pharmaceutical Laboratories, Kissei Pharmaceutical Co., Ltd.,

• Matsumoto Hisao

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Suzuki Toshikazu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Yamada T

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• TOMIOKA Kenichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• YAMADA Toshimitsu

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,

• SAITO Munetoshi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.

• NAGAOKA Hitoshi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• HARA Hiromu

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• TAKANUKI Kenichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• MASE Toshiyasu

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• Tomioka K

  Graduate School Of Pharmaceutical Sciences Kyoto University

• Saito M

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Suzuki T

  Research Unit Of Pharmaceutics College Of Pharmacy Nihon University

• Yamada Takehisa

  Research And Development Division Hokuriku Seiyaku Co. Ltd.

• Sugihara T

  Faculty Of Pharmaceutical Sciences Tokushima Bunri University

• Saito T

  Research And Development Laboratories Maruho Co. Ltd.

• Hara H

  (present Address)corporate Planning Dept. Yamanouchi Pharmaceutical Co. Ltd.

• Mase T

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Suzuki Takeshi

  Institute For Molecular And Cellular Regulation Gunma University

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