2. Academic Validation
  3. Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists

Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists

  • ACS Med Chem Lett. 2016 Dec 13;8(1):107-112. doi: 10.1021/acsmedchemlett.6b00415.
Isamu Sugimoto 1,  Tohru Kambe 2,  Tomotaka Okino 2,  Tetsuo Obitsu 2,  Nobukazu Ohta 2,  Taihei Nishiyama 2,  Akihiro Kinoshita 2,  Taku Fujimoto 2,  Hiromu Egashira 2,  Shinsaku Yamane 2,  Satoshi Shuto 3,  Kousuke Tani 2,  Toru Maruyama 2
Affiliations

Affiliations

  • 1 Medicinal Chemistry Research Laboratories, Department of Biology & Pharmacology, and Discovery Research Alliance, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan; Faculty of Pharmaceutical Sciences and Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.
  • 2 Medicinal Chemistry Research Laboratories, Department of Biology & Pharmacology, and Discovery Research Alliance, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
  • 3 Faculty of Pharmaceutical Sciences and Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan; Faculty of Pharmaceutical Sciences and Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.
PMID: 28105284 DOI: 10.1021/acsmedchemlett.6b00415
Abstract

A novel series of prostaglandin analogues with a seven-membered ring scaffold was designed, synthesized, and evaluated for the functional activation of prostaglandin receptors to identify potent and subtype-selective FP and EP3 dual agonists. Starting from the prostacyclin derivative 5b, a nonselective agonist for prostaglandin receptors, replacement of the core structure with an octahydro-2H-cyclopenta[b]oxepine scaffold led to the discovery of the potent and selective FP and EP3 dual agonist 11b as a lead compound for the development of an antiglaucoma agent.

Keywords

EP3 receptor; FP receptor; GPCR; Prostaglandin; dual agonist; glaucoma.

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