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.