Studies no Nonpeptide Angiotensin II Receptor Antagonists. I. Synthesis and Biological Evaluation of Pyrazolo[1,5-b][1,2,4]triazole Derivatives with Alkyl Substituents
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概要
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Alkyl-substituted pyrazolo[1,5-b][1,2,4]triazole derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Molecules with the (methylbiphenyly)tetrazole moiety at N-5 were the preferred compounds. Ethyl substitutions a both C-2 and C-7 resulted in the optimal compound, 2,7-diethyl-5-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]triazole (5n), with a pA_2 value of 8.74 in rabbit aorta. In the in vivo tests, 5n inhibited the angiotensin II-induced pressor response in rats after oral administration. This compound also produced a dose-dependent decrease in blood pressure when administered orally to conscious furosemide-treated dogs, having a longer duration of action as compared to DuP 753. These data suggest that 5n may be a useful agent for the treatment of angiotensin II-dependent disease, such as hypertension.
- 公益社団法人日本薬学会の論文
- 1998-01-15
著者
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FUJIMORI Akira
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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渡辺 敏子
School Of Pharmaceutical Sciences Toho University
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Okazaki T
Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn
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Okazaki Toshio
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Fujimori Akira
アステラス製薬研究本部薬理研究所
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Fujimori Akira
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Watanabe Toshifumi
Pharmaceutical Research Laboratories Ii Pharmaceutical Research Division Takeda Chemical Industries
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KURIHARA Hiroyuki
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
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Yanagisawa I
Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn
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Yanagisawa Isao
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.
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Yanagisawa Isao
山之内製薬
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Fujimori Akira
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Watanabe T
Chiba Univ. Chiba Jpn
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KIKUCHI Kazumi
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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Kikuchi Kazumi
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Watanabe Toshiko
Faculty Of Pharmaceutical Sciences Chiba University
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Watanabe Toshiko
Graduate School Of Pharmaceutical Sciences Chiba University
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Watanabe Toshihiro
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Shibasaki Masayuki
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.
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Shibasaki Masayuki
General Education Courses Faculty Of Engineering Toyo University
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Kurihara H
Graduate School Of Pharmaceutical Sciences Chiba University
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Kikuchi K
Graduate School Of Pharmaceutical Sciences The University Of Tokyo:presto Jst Corporation
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Inagaki Osamu
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.
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Fujimori Akira
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.
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SUGA Akira
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
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YANAGISAWA Isao
(Present address)Corporate Planning Department, Yamanouchi Pharmaceutical Co., Ltd.,
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Suga Akira
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Kubota H
Chemistry Research Laboratories Astellas Pharmaceutical Inc.
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Kurihara H
Chemistry Research Laboratories Astellas Pharmaceutical Inc.
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