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Discovery of highly selective EP4 receptor agonists that stimulate new bone formation and restore bone mass in ovariectomized rats |
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| Authors: | 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 |
| Affiliation: | Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. kimberly.o.cameron@pfizer.com |
| 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. |
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