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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry*
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Anti-Inflammatory Agents / pharmacology
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Arachidonate 5-Lipoxygenase / chemistry*
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Inhibitory Concentration 50
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Intramolecular Oxidoreductases / antagonists & inhibitors
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Intramolecular Oxidoreductases / chemistry*
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Lipoxygenase Inhibitors / chemical synthesis*
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Lipoxygenase Inhibitors / chemistry*
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Lipoxygenase Inhibitors / pharmacology
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Models, Biological
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Molecular Structure
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Naphthols / chemistry*
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Prostaglandin-E Synthases
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Pyrimidines / chemistry*
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Lipoxygenase Inhibitors
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Naphthols
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Pyrimidines
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pirinixic acid
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Arachidonate 5-Lipoxygenase
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Intramolecular Oxidoreductases
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Prostaglandin-E Synthases