title: Novel benzoxazole inhibitors of mPGES-1.
abstract: A novel series of potent benzoxazole mPGES-1 inhibitors has been derived from a hit from a high throughput screen. Compound 37 displays mPGES-1 inhibition in an enzyme assay (0.018 μM) and PGE-2 inhibition in a cell-based assay (0.034 μM). It demonstrates 500- and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1α, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7 h half-life.
authors.affiliation: Pfizer Research Technology Center, 620 Memorial Dr., Cambridge, MA 02139, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kablaoui
authors.forename: Snahel
authors.initials: S
authors.lastname: Patel
authors.forename: Jay
authors.initials: J
authors.lastname: Shao
authors.forename: Douglas
authors.initials: D
authors.lastname: Demian
authors.forename: Keith
authors.initials: K
authors.lastname: Hoffmaster
authors.forename: Francioise
authors.initials: F
authors.lastname: Berlioz
authors.forename: Michael L
authors.initials: ML
authors.lastname: Vazquez
authors.forename: William M
authors.initials: WM
authors.lastname: Moore
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nugent
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D000071876:Prostaglandin-E Synthases; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases