Biarylimidazoles as inhibitors of microsomal prostaglandin E2 synthase-1.
Microsomal prostaglandin E(2) synthase (mPGES-1) represents a potential target for novel analgesic and anti-inflammatory agents. High-throughput screening identified several leads of mPGES-1 inhibitors which were further optimized for potency and selectivity. A series of inhibitors bearing a biaryl imidazole scaffold exhibits excellent inhibition of PGE(2) production in enzymatic and cell-based assays. The synthesis of these molecules and their activities will be discussed.
Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada.
Tom Y H
TY
Wu
Hélène
H
Juteau
Yves
Y
Ducharme
Richard W
RW
Friesen
Sébastien
S
Guiral
Lynn
L
Dufresne
Hugo
H
Poirier
Myriam
M
Salem
Denis
D
Riendeau
Joseph
J
Mancini
Christine
C
Brideau
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D057166:High-Throughput Screening Assays; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D000071876:Prostaglandin-E Synthases
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone