Selective PGHS-2 Inhibitors: A Rational Approach for Treatment of theInflammation

Author(s): C. R. Rodrigues, M. P. Veloso, H. Verli, C. A.M. Fraga, A. L.P. Miranda, E. J. Barreiro.

Journal Name: Current Medicinal Chemistry

Volume 9 , Issue 8 , 2002

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Abstract:

Prostaglandin-H synthase exists in two isoforms, PGHS-1 and PGHS-2. PGHS-1 is present and is constitutively expressed in most cells and tissues, whereas PGHS-2 is mainly thought to mediate inflammation. Selective prostaglandin-H synthase-2 (or cyclooxygenase-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). This review addresses the main classes of the selective PGHS-2 inhibitors whose selectivity is documented by supporting PGHS-1 and PGHS-2 enzyme data. In addition, we also describe our experience in design, synthesis and pharmacological in vivo evaluation of new 1,2-benzodioxole derivatives as candidate of the selective PGHS-2 inhibitors, with special attention to molecular dynamics simulations of these derivatives attached to the active site of PGHS-2.

Keywords: nsaids, pghs-2 inhibitors, 3d-pharmacophore model, molecular dynamics, acety isalicylic acid, diclofenac, sulindac, indomethacin, piroxicam, selective pghs-2 inhibitors, 1,2-diarylcyclopentenes

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Article Details

VOLUME: 9
ISSUE: 8
Year: 2002
Page: [849 - 867]
Pages: 19
DOI: 10.2174/0929867024606786
Price: $58

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