Discovery and Synthesis of a Potent, Selective and Orally Bioavailable EP4 Receptor Agonist

Abstract

An optimized analog of prostaglandin E 2 which incorporates a γ-lactam in place of the cyclopentanone ring and which incorporates metabolically stabilized side chains, has been identified and shown to exhibit potent and selective EP4 receptor agonism.The compound (2) (L-000902688) is also well absorbed on oral dosing and exhibits a long half-life making it an excellent tool for the study of the role of EP4 receptor in physiology and disease.An efficient synthesis of 2 from a chiral synthon is described.