Design and synthesis of a selective EP4-receptor agonist. Part 1: Discovery of 3,7-dithiaPGE1 derivatives and identification of their ω chains

Article abstract of DOI:10.1016/S0968-0896(01)00351-0

Improvement of EP4-receptor selectivity and the agonist activity by introduction of heteroatoms into the α chain of PGE₁ was investigated. Among the compounds tested, 3,7-dithiaPGE₁ 4a exhibited good EP4-receptor selectivity and agonist activity. Further modification of the ω chain of 3,7-dithiaPGE₁ was performed to improve EP4-receptor selectivity and agonist activity. Of the compounds produced, 16-phenyl-ω-tetranor-3,7-dithiaPGE₁ 4p possessing moderate EP4-receptor selectivity and agonist activity, was identified as a new chemical lead for further optimization by modification of the aromatic moiety. Copyright