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

作者：Hieke Martina; Greiner Christine; Thieme Theresa M; Schubert Zsilavecz Manfred; Werz Oliver; Zettl Heiko^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(5): 1329-1333.

DOI：10.1016/j.bmcl.2011.01.049

• Inflammation
• Arachidonic acid cascade
• SAR
• mPGES-1
• 5-LO

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 alpha-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 mu M; IC(50) 5-LO = 0.1 mu M) showing the most favorable in vitro pharmacological profile.

• 出版日期2011-3-1