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

  • J Med Chem. 2018 Aug 9;61(15):6869-6891. doi: 10.1021/acs.jmedchem.8b00808.
Ryo Iwamura  1 ,  Masayuki Tanaka  1 ,  Eiji Okanari  1 ,  Tomoko Kirihara  2 ,  Noriko Odani-Kawabata  2 ,  Naveed Shams  2  3 ,  Kenji Yoneda  1
Affiliations
  • 1. Pharmaceuticals Research Laboratory , UBE Industries, Ltd. , 1978-5 Kogushi , Ube , Yamaguchi 755-8633 , Japan.
  • 2. R&D Division , Santen Pharmaceutical Co., Ltd. , Grand Front Osaka Tower A 4-20, Ofukacho , Kita-ku , Osaka 530-8552 , Japan.
  • 3. R&D Division , Santen Inc. , 6401 Hollis Street, Suite 125 , Emeryville , California 94608 , United States.
PMID: 29995405 DOI: 10.1021/acs.jmedchem.8b00808
Abstract

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.

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