Development of a highly selective EP2-receptor agonist. Part 1: identification of 16-hydroxy-17,17-trimethylene PGE2 derivatives

Design and synthesis of an EP2-receptor selective agonist began with the chemical modification of α- and ω-chains of butaprost 1a, which exhibits an affinity for the IP-receptor. Two series of prostaglandin (PG) analogues with a 16-hydroxy-17,17-trimethylene moiety as an ω-chain were identified. Among those tested, 4a,b,e,f,h and 6a,b,e,f,h were found to be highly selective EP2-receptor agonists. Structure–activity relationships are discussed. Two series of prostaglandin analogues 4a,b,e,f,h and 6a,b,e,f,h possessing 15-hydroxy-17,17-trimethylene moiety were identied to be potent and selective EP2-receptor agonists.