Synthesis and Evaluation of 1-Arylsulfonyl-3-piperazinone Derivatives as a Factor Xa Inhibitor II. Substituent Effect on Biological Activities
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概要
- 論文の詳細を見る
Intravascular clot formation is an important event in a number of cardiovascular diseases. The prevention of blood coagulation has become a major target for new therapeutic agents. Factor Xa (FXa) is a trypsin-like serine protease that plays a key role in the blood coagulation cascade and represents an attractive target for anticoagulant drug development. We have investigated substituents in the central part of a lead compound (3:M55113), and discovered that compound M55551 (34:(R)-4-[(6-Chloro-2-naphthalenyl)sulfonyl]-6-oxo-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]-2-piperazinecarboxylic acid) is a potent inhibitor of FXa (IC_<50>=0.006μM), with high selectivity for FXa over trypsin and thrombin. The activity of this compound is ten times more powerful than the lead compound.
- 公益社団法人日本薬学会の論文
- 2002-09-01
著者
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Miyazaki Yutaka
Discovery Research Center Mochida Pharmaceutical Co. Ltd.
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Mizuno Masashi
Division Of Science Of Biological Resources The Graduate School Of Science And Technology
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Mizuno Masashi
Division Of Life Science Graduate School Of Science And Technology Kobe University
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Mizuno Masashi
Graduate School Of Science And Technology Kobe University
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Mizuno Masashi
Nagano Japan Radio Co. Ltd. Currently With Kyushu Institute Of Technology
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Okamoto A
Discovery Research Center Mochida Pharmaceutical Co. Ltd.
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Mizuno M
Kobe Univ. Kobe Jpn
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MOCHIZUKI Hidenori
Discovery Research Center, Mochida Pharmaceutical Co., Ltd.
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NISHIDA Hidemitsu
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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MIYAZAKI Yutaka
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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MUKAIHIRA Takafumi
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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SAITOH Fumihiko
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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FUKUI Miyuki
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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HARADA Kousuke
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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ITOH Manabu
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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MURAOKA Aki
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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MATSUSUE Tomokazu
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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OKAMOTO Atsushi
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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HOSAKA Yoshitaka
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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MATSUMOTO Miwa
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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OHNISHI Shuhei
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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MOCHIZUKI Hidenori
Chemistry Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
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Itoh M
Chemistry Laboratory Research Center Mochida Pharmaceutical Co. Ltd.
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Okamoto Atsushi
Discovery Research Center Mochida Pharmaceutical Co. Ltd.
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Muraoka Aki
Chemistry Laboratory Research Center Mochida Pharmaceutical Co. Ltd.
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Fukui M
Discovery Research Center Mochida Pharmaceutical Co. Ltd.
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Harada K
Roman Industries Co. Ltd.
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SAITOH Fumihiko
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.
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NISHIDA Hidemitsu
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.
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MUKAIHIRA Takafumi
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.
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MATSUSUE Tomokazu
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.
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HOSAKA Yoshitaka
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.
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Miyazaki Y
Department Of Pharmacy. Tokyo Women's Medical University Medical Center East:department Of Phar
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Mizuno M
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd.
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Morimoto M
Graduate School Of Science And Technology Kobe University
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Saitoh F
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd.
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Hosaka Y
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd.
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Matsusue Tomokazu
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd.
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Nishida H
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd.
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Mochizuki Hidenori
Discovery Research Center Mochida Pharmaceutical Co. Ltd.
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Mukaihira Takafumi
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd.
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