Design and Synthesis of a Selective EP4-Receptor Agonist. Part 2: 3,7-DithiaPGE1 Derivatives with High Selectivity

Abstract

To identify new highly selective EP4-agonists, further modification of the 16-phenyl moiety of 1 was continued. 16-(3-Methoxymethyl)phenyl derivatives 13-6q and 16-(3-ethoxymethyl)phenyl derivatives 13-7e showed more selectivity and potent agonist activity than 1. 16-(3-Methyl-4-hydroxy)phenyl derivative 18-14e demonstrated excellent subtype selectivity, while both its receptor affinity and agonist activity were less potent than those of 13-6q. Structure–activity relationships (SARs) are also discussed.