Discovery of R-142086 as a Factor Xa (FXa) Inhibitor : Syntheses and Structure-Activity Relationships of Cinnamyl Derivatives
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概要
- 論文の詳細を見る
To develop a novel and effective anticoagulant with potent and selective factor Xa (FXa) inhibitory activity, a new series of cinnamyl derivatives with enhanced lipophilicity and prodrug forms were synthesized and their biological activities were evaluated. As a result, we found that cinnamyl derivative (N-{4-[1-(acetimidoyl)-piperidin-4-yloxyl-3-carbamoylphenyl}-N-[(Z)-3-(3-amidinophenyl)-2-fluoro-2-propenyl]sulfamoyl)acetic acid dihydrochloride (26d, R-142086) with a fluorine atom on the double bond exhibited potent anticoagulant activity and no mutagenic potential. Moreover, orally administered R-142086 exhibited potent anti-FXa activity and anticoagulant activity in dogs.
- 公益社団法人日本薬学会の論文
- 2009-01-01
著者
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Tanaka N
Department Of Pharmacology School Of Pharmaceutical Sciences Mukogawa Women's University
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Tanaka Naoko
武庫川女子大学 薬学部薬理学
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中西 務
Faculty Of Pharmaceutical Sciences Setsunan University
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Tanaka N
School Of Pharmaceutical Sciences Mukogawa Women S University
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Ishizuka Tomoko
R & D Division Daiichi Sankyo Co. Ltd.
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Ogawa T
R & D Division Daiichi Sankyo Co. Ltd.
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NOGUCHI Tetsuji
R & D Division, Daiichi Sankyo Co., Ltd.
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TANAKA Naoki
R & D Division, Daiichi Sankyo Co., Ltd.
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NISHIMATA Toyoki
R & D Division, Daiichi Sankyo Co., Ltd.
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GOTO Riki
R & D Division, Daiichi Sankyo Co., Ltd.
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HAYAKAWA Miho
R & D Division, Daiichi Sankyo Co., Ltd.
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SUGIDACHI Atsuhiro
R & D Division, Daiichi Sankyo Co., Ltd.
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OGAWA Taketoshi
R & D Division, Daiichi Sankyo Co., Ltd.
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NIITSU Yoichi
R & D Division, Daiichi Sankyo Co., Ltd.
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ASAI Fumitoshi
R & D Division, Daiichi Sankyo Co., Ltd.
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ISHIZUKA Tomoko
R & D Division, Daiichi Sankyo Co., Ltd.
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FUJIMOTO Koichi
R & D Division, Daiichi Sankyo Co., Ltd.
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Goto R
R & D Division Daiichi Sankyo Co. Ltd.
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Hayakawa Miho
R & D Division Daiichi Sankyo Co. Ltd.
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Asai Fumitoshi
R & D Division Daiichi Sankyo Co. Ltd.
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Fujimoto K
R & D Division Daiichi Sankyo Co. Ltd.
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Noguchi Tetsuji
R & D Division Daiichi Sankyo Co. Ltd.
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Niitsu Yoichi
R & D Division Daiichi Sankyo Co. Ltd.
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Sugidachi Atsuhiro
R & D Division Daiichi Sankyo Co. Ltd.
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Nishimata Toyoki
R & D Division Daiichi Sankyo Co. Ltd.
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