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

A 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 selective κ-full agonists are reported. Salvinorin A, a compound isolated from the plant Salvia divinorum, is a potent and highly selective agonist for the κ opioid receptor. For exploration of its structure and activity relationships, further modifications, such as reduction 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 new full agonists have been identified.