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

详细信息    查看全文

• 作者：Isamu SugimotoTohru Kambe ; Tomotaka Okino ; Tetsuo Obitsu ; Nobukazu Ohta ; Taihei Nishiyama ; Akihiro Kinoshita ; Taku Fujimoto ; Hiromu Egashira ; Shinsaku Yamane ; Satoshi Shuto ; Kousuke TaniToru Maruyama
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：January 12, 2017
• 年：2017
• 卷：8
• 期：1
• 页码：107-112
• 全文大小：443K
• ISSN：1948-5875

文摘

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.