Discovery of CP-533536: An EP2 receptor selective prostaglandin E2 (PGE2) agonist that induces local bone formation

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.

Graphical abstractWe describe the synthesis, SAR, and in vivo efficacy of a series of EP2-selective sulfonamide derivatives.Figure optionsDownload full-size imageDownload as PowerPoint slide