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Discovery of highly selective EP4 receptor agonists that stimulate new bone formation and restore bone mass in
Kimberly O Cameron1, Bruce A Lefker, Margaret Y Chu-Moyer
1Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. kimberly.o.cameron@pfizer.com
Bioorganic & Medicinal Chemistry Letters
|January 31, 2006
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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