Synthesis and in vitro dopaminergic activity of (2-aminoethyl)-1-hydroxy-2-pyridone type dopamine analogs

Two isoteric/isoelectronic dopamine analogs based of (2'-aminoethyl)-1-hydroxy-2-pyridone without having the COMT vulnerable m-hydroxy group were synthesized via ten synthetic steps. Their dopaminergic activities were evaluated by measuring the inhibitory effects of prolactin secretion from the anterior pituitary in rats. The compounds 1 and 2 caused a reduction of prolactin secretion at the 10(-6) M concentration. Semiempirical MO calculations (at the AM-1 level) were performed on 1 and 2 in order to understand the structural and electronic features as compared to dopamine.