2. Academic Validation
  3. Modified acidic nonsteroidal anti-inflammatory drugs as dual inhibitors of mPGES-1 and 5-LOX

Modified acidic nonsteroidal anti-inflammatory drugs as dual inhibitors of mPGES-1 and 5-LOX

  • J Med Chem. 2012 Oct 25;55(20):8958-62. doi: 10.1021/jm3010543.
Mahmoud Elkady 1,  Raimund Nieß,  Anja M Schaible,  Julia Bauer,  Susann Luderer,  Giulia Ambrosi,  Oliver Werz,  Stefan A Laufer
Affiliations

Affiliation

  • 1 Department of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University, Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.
PMID: 22992107 DOI: 10.1021/jm3010543
Abstract

mPGES-1 is a promising target for development of new anti-inflammatory drugs. We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by replacing the carboxylic acid functionality by sulfonamide moieties. Compounds were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC₅₀ = 0.16 μM), while the best 5-LOX inhibition was attained by indomethacin derivative 17 (IC₅₀ = 0.9 μM). Inhibition of COX-1 activity was completely removed.

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