Spectral and crystallographic study of pyridinic analogues of nimesulide:: Determination of the active form of methanesulfonamides as COX-2 selective inhibitors

被引：33
作者：
Julémont, F
de Leval, X
Michaux, C
Damas, J
Charlier, C
Durant, F
Pirotte, B
Dogné, JM
机构：
[1] Univ Liege, Dept Med Chem, Nat & Synth Drugs Res Ctr, B-4000 Liege, Belgium
[2] Univ Namur, Dept Mol & Struct Chem, B-5000 Namur, Belgium
[3] Univ Liege, Dept Human Physiol, B-4020 Liege, Belgium
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 23期
关键词：
D O I：
10.1021/jm020920n
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Compound 7, N-(3-phenoxy-4-pyridinyl)trifluoromethanesulfonamide, showed in vitro (whole blood assay) a strong inhibitory activity on the two cyclooxygenase (COX) enzymes (IC50(COX-1) = 2.2 muM and IC50(COX-2) = 0.4 muM), being more active but less COX-2-selective than nimesulide. Physicochemical studies and structural analyses indicated that the anionic sulfonamidate species seemed to be the active form of methanesulfonamides, which optimally interacted with the COX enzymes' active sites.
引用
收藏
页码：5182 / 5185
页数：4
相关论文
共 16 条
  • [1] ALBERT A, 1971, DETERMINATION IONIZA, P342
  • [2] Synthesis and pharmacological evaluation of derivatives structurally related to nimesulide
    Cignarella, G
    Vianello, P
    Berti, F
    Rossoni, G
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1996, 31 (05) : 359 - 364
  • [3] Crofford LJ, 2000, ARTHRITIS RHEUM-US, V43, P4, DOI 10.1002/1529-0131(200001)43:1<4::AID-ANR2>3.0.CO
  • [4] 2-V
  • [5] Cyclooxygenase inhibitors - current status and future prospects
    Dannhardt, G
    Kiefer, W
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (02) : 109 - 126
  • [6] Evaluation of classical NSAIDs and COX-2 selective inhibitors on purified ovine enzymes and human whole blood
    de Leval, X
    Delarge, J
    Devel, P
    Neven, P
    Michaux, C
    Masereel, B
    Pirotte, B
    David, JL
    Henrotin, Y
    Dogné, JM
    [J]. PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 2001, 64 (4-5): : 211 - 216
  • [7] SYNTHESIS OF POLYNUCLEAR HETEROCYCLES .2. CYCLISATIONS OF 2-SUBSTITUTED AND 4-SUBSTITUTED 3-AMINO-PYRIDINES AND 3-NITRO-PYRIDINES
    EATOUGH, JJ
    FULLER, LS
    GOOD, RH
    SMALLEY, RK
    [J]. JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1970, (13): : 1874 - &
  • [8] Griswold DE, 1996, MED RES REV, V16, P181, DOI 10.1002/(SICI)1098-1128(199603)16:2<181::AID-MED3>3.0.CO
  • [9] 2-X
  • [10] Design and synthesis of 4,5-diphenyl-4-isoxazolines: Novel inhibitors of cyclooxygenase-2 with analgesic and antiinflammatory activity
    Habeeb, AG
    Rao, PNP
    Knaus, EE
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (18) : 2921 - 2927
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