Studies on Nonpeptide Angiotensin II Receptor Antagonists. III. Synthesis and Biological Evaluation of 5-Alkylidene-3,5-dihydro-4H-imidazol-4-one-Derivatives

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概要

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• 5-Alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Substitutions at C-2 and C-5,respectively, with a propyl group and a 1-methylethylidene group resulted in the optimal compound, 3,5-dihydro-5-(1-methylethylidene)-2-propyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-4H-imidazol-4-one (2b), with a pA_2 value of 8.85 in rabbit aorta. When administered orally to rats 2b showed a greater inhibitory effect on angiotesin II-induced pressor response than DuP 753. Compound 2b also showed a good antihypertensive effect when administered orally to conscious sodium-depleted spontaneously hypertensive rats, with a duration of action of 24 h. These data suggest that 2b may be a useful agent for the treatment of angiotensin II-dependent diseases such as hypertension.

• 公益社団法人日本薬学会の論文
• 1998-05-15

著者

• FUJIMORI Akira

  Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• 渡辺 敏子

  School Of Pharmaceutical Sciences Toho University

• Okazaki T

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Okazaki Toshio

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Fujimori Akira

  アステラス製薬研究本部薬理研究所

• Fujimori Akira

  Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Watanabe Toshifumi

  Pharmaceutical Research Laboratories Ii Pharmaceutical Research Division Takeda Chemical Industries

• Yanagisawa I

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Yanagisawa Isao

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Yanagisawa Isao

  山之内製薬

• Fujimori Akira

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Watanabe T

  Chiba Univ. Chiba Jpn

• KIKUCHI Kazumi

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

• Kikuchi Kazumi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Watanabe Toshiko

  Faculty Of Pharmaceutical Sciences Chiba University

• Watanabe Toshiko

  Graduate School Of Pharmaceutical Sciences Chiba University

• Watanabe Toshihiro

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Shibasaki Masayuki

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Shibasaki Masayuki

  General Education Courses Faculty Of Engineering Toyo University

• Kikuchi K

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo:presto Jst Corporation

• Inagaki Osamu

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Fujimori Akira

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• SUGA Akira

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

• Suga Akira

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

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