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

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• 作者：Martina Hieke^a ; ^† ; ; Christine Greiner^b ; ^† ; ; Theresa M. Thieme^a ; Manfred Schubert-Zsilavecz^a ; Oliver Werz^b ; Heiko Zettl^c ; ^{heiko.zettl@pharma.ethz.ch}
• 关键词：Inflammation ; Arachidonic acid cascade ; SAR ; mPGES-1 ; 5-LO
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 March 2011
• 年：2011
• 卷：21
• 期：5
• 页码：1329-1333
• 全文大小：1403 K

文摘

Dual inhibition of microsomal prostaglandin E₂ 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 (IC₅₀ mPGES-1 = 0.94 μM; IC₅₀ 5-LO = 0.1 μM) showing the most favorable in vitro pharmacological profile.