Synthesis and in vitro pharmacological studies of C(4) modified salvinorin A analogues

Salvinorin A is the most potent naturally occurring opioid agonist with a high selectivity and affinity for κ-opioid receptor. To explore its structure–activity relationships, modifications at the C(4) position have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for binding and functional activities at the human κ-opioid receptor and several potent new agonists have been identified.

Graphical abstractA series of salvinorin A derivatives modified at the C(4) position were prepared and screened for binding and functional activities at the human κ-opioid receptor. Several highly selective κ-full agonist are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide