Ethenesulfonamide Derivatives, a Novel Class of Orally Active Endothelin-A Receptor Antagonists
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概要
- 論文の詳細を見る
In the present article we wish to report the discovery of a novel class of ET_A-selective endothelin(ET)receptor antagonists through the modification of the ET_A/ET_B non-selective antagonist, Ro47-0203(Bosentan, 1). Replacement of the benzenesulfonamide group of 1 with a 2-phenylethenesulfonamide group gave compound 5a and resulted in improvement in ET_A-selectivity. Optimization of the alkoxy side chain attached to the core pyrimidine ring yielded the 2-fluoroethoxy derivative(5n)with further improvement of ET_A-selectivity. [IC_<50>=2.1nM for ET_A receptor, ET_B/ET_A ratio=1200]. After oral administration, compound 5n inhibited the big ET-1 induced pressor response in pithed rats with a DR_2 value of 2.6mg/kg and also exhibited a potent antagonistic activity in conscious rats.
- 公益社団法人日本薬学会の論文
- 2001-05-01
著者
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FUJIMORI Akira
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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原田 博史
Dainippon Pharmaceutical Co. Ltd.
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TANAKA Akihiro
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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Tanaka A
Faculty Of Pharmaceutical Sciences Tokyo University Of Science
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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 A
Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn
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Fujimori Akira
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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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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Tanaka Akihiro
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Harada H
Laboratory Of Medicinal Plant Science Tokyo University Of Pharmacy And Life Science School Of Pharma
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HARADA Hironori
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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KAZAMI Jun-ichi
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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WATANUKI Susumu
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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TSUZUKI Ryuji
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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SUDOH Katsumi
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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TSUKAMOTO Shin-ichi
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
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Kazami Jun-ichi
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Tsuzuki R
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Tsuzuki Ryuji
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Sudoh K
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Fujimori Akira
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.
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Watanuki S
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Watanuki Susumu
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Harada H
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Tsukamoto S
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.ltd.
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Tsukamoto Shin-ichi
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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Sudoh Katsumi
Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.
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