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

Basic Information

ID: ALA1681685

Journal: Bioorg Med Chem Lett

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

Authors: Hieke M, Greiner C, Thieme TM, Schubert-Zsilavecz M, Werz O, Zettl H.

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.

CiteXplore: 21310608

DOI: 10.1016/j.bmcl.2011.01.049

Patent ID: