Synthesis of <i>N</i>-alkylated octopamine derivatives and their interaction with octopamine receptor BmOAR1

A series of <i>N</i>-alkylated octopamine derivatives was synthesized, and the structure-activity relationships of these derivatives with the silkworm <i>Bombyx mori</i> octopamine receptor BmOAR1 were evaluated using a secreted placental alkaline phosphatase reporter assay system. The <i>N</i>-alkyl moiety on the ligand affected the intensity of the agonist activity in the order: CH₃>(H)>C₂H₅. Although linear alkyl chains of C3 or higher did not exhibit any activity, the fixed C3 alkyl group forming a pyrrolidine ring showed significant activity. These results suggest that BmOAR1 has a relatively small space around the amine-binding site, and the alkyl part constituting the cyclic amine could exert the same effect as the small alkyl group.