Synthesis and Thromboxane A_2 Antagonistic Activity of [[1-Aryl(or Benzyl)-1-(benzenesulfonamide)methyl]phenyl]alkanoic Acid Derivatives
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概要
- 論文の詳細を見る
In order to find new antiasthematic and antithrombotic agents, various [[1-aryl(or benzyl)-1-(benzenesulfonamido)methyl]phenyl]alkanoic acids derivatives were synthesized. Evaluation of these compounds for thromboxane A_2 (TXA_2) antagonistic activities indicated that 4-[4-[(4-chlorobenzenesulfonamido)phenylmethyl]phenyl]butyric acid (6h), 4-[4-[1-(4-chlorobenzenesulfonamido)-2-phenylethyl]butyric acid (6y) and many other compounds have potent inhibitory effects on U-46619-induced guinea-pig platelet aggregation. No significant difference in the inhibitory effect between (+)-6h and its antipode could be detected, although (+)-6y was about 10 times more potent than (-)-6y. The pK_b values of 6h and 6y were estimated to be 8.9 and 10,respectively on U-46619-induced contraction of guinea-pig trachea as a pharmacological measure of TXA_2 antagonistic activity. These compounds also showed potent inhibitory effects on U-46619-induced bronchoconstriction in guinea-pig after oral administration in vivo. They were also evaluated for other related pharmacological effects involving the arachidonic acid cascade. It ws found that these compounds possess TXA_2 synthase inhibitory activity together with TXA_2 antagonistic activity, and 6h also possesses weak leukotriene D_4 (LTD_4) antagonistic acitivity. Structure-activity relationships for TXA_2 antagonistic activity of these derivatives are discussed.
- 社団法人日本薬学会の論文
- 1996-04-15
著者
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斎藤 徹
Faculty Of Pharmaceutical Sciences Kanazawa University
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Ito Y
Mukogawa Women's Univ. Hyogo Jpn
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YOSHIZUMI Satoshi
Kyoto Pharmaceutical University
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Yoshizumi S
Research And Development Headquaters Hokuriku Seivaku Co. Ltd.
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Kato K
Toho Univ. Chiba Jpn
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Kato K
Grad. Sch. Pharm. Sci. Nagoya City Univ.:okazaki Inst. Integ. Biosci. Natl. Inst. Natl. Sci.
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Suzuki T
Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.
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Yasuda S
Kanazawa Univ. Kanazawa Jpn
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Yasuda Shingo
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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Kato H
Research And Development Headquarters Hokurikit Seiyaku Co. Ltd.
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Kato H
Teikyo Univ. Kanagawa Jpn
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ITO Yasuo
Research Center for Nuclear Science and Technology, The University of Tokyo
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Suzuki T
Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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SAKURAI Shunichiro
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
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OGAWA Nobuo
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
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OHASHI Tetsuo
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
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KATO Ken-ichi
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
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KATO Hideo
Research and Development Division, Hokuriku Seiyaku Co., Ltd.,
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SAKURAI Shuniciro
Research and development Division, Hokuriku Seiyaku Co., Ltd.,
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SUZUKI Tomio
Research and development Division, Hokuriku Seiyaku Co., Ltd.,
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Saito Takako
Research And Development Laboratories Maruho Co. Ltd.
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Kato Ken-ichi
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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Suzuki Toshikazu
Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.
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Ito Yasuo
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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Kato Hideo
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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Yasuda Satoshi
Department Of Biological Chemistry Faculty Of Pharmaceutical Sciences Nagoya City University
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Ogawa Nobuo
Department Of Biotechnology Faculty Of Engineering Osaka University
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Ogawa Nobuo
Department Of Mechanical Engineering Faculty Of Science And Technology Science University Of Tokyo
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Ohashi Tetsuo
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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Ohashi Tetsuo
Research And Development Division Hokuriku Seiyaku Co. Ltd
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Suzuki T
Research Unit Of Pharmaceutics College Of Pharmacy Nihon University
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Sakurai S
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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Kato Koichi
Okazaki Institute For Integrative Bioscience Institute For Molecular Science
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Ohashi T
Research And Development Division Hokuriku Seiyaku Co. Ltd.
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