Studies on Anti-inflammatory Agents. IV. Synthesis and Pharmacological Properties of 1,5-Diarylpyrazoles and Related Derivatives
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概要
- 論文の詳細を見る
A series of novel 1,5-diarylpyrazole derivatives was synthesized and tested for anti-inflammatory and analgesic activities to develop anti-inflammatory agents with fewer side effects than existing nonsteroidal anti-inflammatory drugs. The structure-activity relationships in this series were extensively studied. Electron-withdrawing substituents such as NC and CF_3 were optimal at the 3-position of the pyrazole ring. Replacement of these substituents with bulky ones gave less active compounds. The 4-(methylsulfonyl)phenyl group seemed to be the optimal group at the 5-position of the pyrazole ring. The most potent compound was 1-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-pyrazole-3-carbonitrile (19a), with oral ED_<50> values of 0.030 and 0.47mg/kg on adjuvant-induced arthritis and collagen-induced arthritis, respectively, and an ED_<30> value of 7.4mg/kg in the yeast-induced hyperalgesia (Randall-Selitto) assay. Compound 19a also showed potent inducible cyclooxygenase (COX-2)-inhibitory activity (IC_<50>=0.24μM) with no COX-1 inhibition even at 100μM.
- 社団法人日本薬学会の論文
- 1997-06-15
著者
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辻 浩一
Microbiological Research Institute Otsuka Pharmaceutical Co. Ltd.
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Nakamura Katsuya
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Ochi Takehiro
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Tsuji Kiyoshi
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Matsuo Masaaki
New Drug Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Ogino T
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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TSUJI Kiyoshi
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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KONISHI Nobukiyo
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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NAKAMURA Katsuya
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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TOJO Takashi
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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OCHI Takehiro
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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SENOH Hachiro
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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Matsuo Masaaki
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Nakamura Kazufumi
Faculty Of Pharmaceutical Sciences Kyushu University
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TOJO Takashi
Research Laboratory, Higeta Shoyu Co., Ltd.
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Nakamura Katsuji
Tsukuba Research Laboratories Eisai Co. Ltd.
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Tsuji K
School Of Pharmaceutical Science University Of Shizuoka
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辻 京子
Faculty Of Pharmaceutical Sciences Setsunan University
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Tojo T
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Tojo Takashi
Research Laboratory Higeta Shoyu Co. Ltd.
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Tojo Takashi
Up Educational Project
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Ogino T
Research Division Discovery Research Laboratories Ii Sumitomo Pharmaceuticals Co. Ltd.
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Senoh Hachiro
New Drug Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Konishi N
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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