2. Academic Validation
  3. A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold

A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold

  • Bioorg Med Chem Lett. 2011 Mar 1;21(5):1329-33. doi: 10.1016/j.bmcl.2011.01.049.
Martina Hieke 1,  Christine Greiner,  Theresa M Thieme,  Manfred Schubert-Zsilavecz,  Oliver Werz,  Heiko Zettl
Affiliations

Affiliation

  • 1 Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry/ZAFES/LiFF, Frankfurt/M, Germany.
PMID: 21310608 DOI: 10.1016/j.bmcl.2011.01.049
Abstract

Dual inhibition of microsomal prostaglandin E(2) synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) represents a promising strategy in the development of novel anti-inflammatory drugs targeting the arachidonic acid cascade. Herein, a class of α-naphthyl pirinixic acids is characterized as dual mPGES-1/5-LO inhibitors. Systematic structural variation was focused on the lipophilic backbone of the scaffold and yielded detailed structure-activity relationships (SAR) with compound 16 (IC(50) mPGES-1=0.94 μM; IC(50) 5-LO=0.1 μM) showing the most favorable in vitro pharmacological profile.

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