title: Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E₂ synthase-1 inhibitors.
abstract: The imidazoquinoline derivative 1 was found as a novel mPGES-1 inhibitor. Optimization of 1 led to the identification of the 2-chlorophenyl group at the C(2)-position and the quinolone structure at the C(4)-position. Compound 33, the most potent synthesized compound, showed excellent mPGES-1 inhibition (IC(50)=9.1nM) with high selectivity (>1000-fold) over both COX-1 and COX-2.
authors.affiliation: Drug Research Division, Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Shiro
authors.forename: Hirotada
authors.initials: H
authors.lastname: Takahashi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kakiguchi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Keiki
authors.initials: K
authors.lastname: Masuda
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Nagata
authors.forename: Masanori
authors.initials: M
authors.lastname: Tobe
mesh_terms: D000641:Ammonia / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D008956:Models, Chemical; D000071876:Prostaglandin-E Synthases; D015363:Quinolones / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D015363:Quinolones; D000641:Ammonia; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse