Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E2 synthase-1 inhibitors

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 (IC50 = 9.1 nM) with high selectivity (>1000-fold) over both COX-1 and COX-2.