Synthesis and evaluation of a γ-lactam as a highly selective EP2 and EP4 receptor agonist

γ-Lactam analogs (2) of EP4 receptor agonists were identified by substitution of the pyrazolidinone ring (1) with a pyrrolidinone ring. Several compounds (such as 2a, 2h) with high potency, selectivity and acceptable PK profiles were discovered. These were assessed in animal models of ovulation induction and bronchoconstriction.

Graphical abstractγ-Lactam analogs (2) of EP4 receptor agonists were identified by substitution of the pyrazolidinone ring (1) with a pyrrolidinone ring. Several compounds (such as 2a, 2h) with high potency, selectivity, and acceptable PK profiles were discovered. These were assessed in animal models of ovulation induction and bronchoconstriction.Figure optionsDownload full-size imageDownload as PowerPoint slide