Discovery of highly selective EP4 receptor agonists that stimulate new bone formation and restore bone mass in ovariectomized rats

…, MY Chu-Moyer, DT Crawford, PDS Jardine…

Index: Cameron, Kimberly O.; Lefker, Bruce A.; Chu-Moyer, Margaret Y.; Crawford, David T.; Jardine, Paul DaSilva; DeNinno, Shari L.; Gilbert, Sandra; Grasser, William A.; Ke, HuaZhu; Lu, Bihong; Owen, Thomas A.; Paralkar, Vishwas M.; Qi, Hong; Scott, Dennis O.; Thompson, David D.; Tjoa, Christina M.; Zawistoski, Michael P. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 7 p. 1799 - 1802

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Citation Number: 32

Abstract

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.