title: A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold.
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.
authors.affiliation: Goethe-University Frankfurt, Institute of Pharmaceutical Chemistry/ZAFES/LiFF, Frankfurt/M, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Hieke
authors.forename: Christine
authors.initials: C
authors.lastname: Greiner
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Thieme
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Heiko
authors.initials: H
authors.lastname: Zettl
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008954:Models, Biological; D015394:Molecular Structure; D009284:Naphthols / Q000737:chemistry*; D000071876:Prostaglandin-E Synthases; D011743:Pyrimidines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D016859:Lipoxygenase Inhibitors; D009284:Naphthols; D011743:Pyrimidines; C006253:pirinixic acid; D001094:Arachidonate 5-Lipoxygenase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases