Discovery of highly selective EP4 receptor agonists that stimulate new bone formation and restore bone mass in ovariectomized rats
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- 作者：Kimberly O. Cameron ; Bruce A. Lefker ; Margaret Y. Chu-Moyer ; David T. Crawford ; Paul DaSilva Jardine ; Shari L. DeNinno ; Sandra Gilbert ; William A. Grasser ; HuaZhu Ke ; Bihong Lu et al.
- 关键词：Bone anabolic agent ; EP4 ; EP2 ; Prostaglandin ; Lactam ; Osteoporosis
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：1 April 2006
- 年：2006
- 卷：16
- 期：7
- 页码：1799-1802
- 全文大小：128 K
文摘
Heptanoic acid lactams, exemplified by 2, were identified as highly selective EP4 agonists via high throughput screening. Lead optimization led to the identification of lactams with a 30-fold increase in EP4 potency in vitro. Compounds demonstrated robust bone anabolic effects when administered in vivo in rat models of osteoporosis.