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Discovery of CP-533536: An EP2 receptor selective prostaglandin E2 (PGE2) agonist that induces local bone formation |
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| Authors: | Kimberly O. Cameron Bruce A. Lefker Hua Z. Ke Mei Li Michael P. Zawistoski Christina M. Tjoa Ann S. Wright Shari L. DeNinno Vishwas M. Paralkar Thomas A. Owen Li Yu David D. Thompson |
| Affiliation: | 1. Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA;2. Amgen Inc., Thousand Oaks, CA 91320, USA;3. Department of Theoretical and Applied Science, Ramapo College, Mahwah, NJ 07430, USA;4. Drug Safety and Disposition, Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA |
| Abstract: | Sulfonamides, exemplified by 3a, were identified as highly selective EP2 agonists. Lead optimization led to the identification of CP-533536, 7f, a potent and selective EP2 agonist. CP-533536 demonstrated the ability to heal fractures when administered locally as a single dose in rat models of fracture healing. |
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