Identification of a Selective, Non-Prostanoid EP2 Receptor Agonist for the Treatment of Glaucoma: Omidenepag and its Prodrug Omidenepag Isopropyl

EP2 receptor agonists are expected
to be effective ocular hypotensive
agents; however, it has been suggested that agonism to other EP receptor
subtypes may lead to undesirable effects. Through medicinal chemistry
efforts, we identified a scaffold bearing a (pyridin-2-ylamino)­acetic
acid moiety as a promising EP2-selective receptor agonist. (6-((4-(Pyrazol-1-yl)­benzyl)­(pyridin-3-ylsulfonyl)­aminomethyl)­pyridin-2-ylamino)­acetic
acid 13ax (omidenepag, OMD) exerted potent and selective
activity toward the human EP2 receptor (h-EP2). Low doses of omidenepag
isopropyl (OMDI), a prodrug of 13ax, lowered intraocular
pressure (IOP) in ocular normotensive monkeys. OMDI was selected as
a clinical candidate for the treatment of glaucoma.