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

Martina Hieke, Christine Greiner, Theresa M Thieme, Manfred Schubert-Zsilavecz, Oliver Werz, Heiko Zettl

Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry/ZAFES/LiFF, Frankfurt/M, Germany.

Bioorganic & medicinal chemistry letters 2011 Mar 1

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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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Citation

Martina Hieke, Christine Greiner, Theresa M Thieme, Manfred Schubert-Zsilavecz, Oliver Werz, Heiko Zettl. A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold. Bioorganic & medicinal chemistry letters. 2011 Mar 1;21(5):1329-33