Design, synthesis, and monoamine transporter binding site affinities of methoxy derivatives of indatraline

A series of methoxy-containing derivatives of indatraline 13a-f and 17 were synthesized, and their binding affinities for the dopamine, serotonin, and norepinephrine transporter binding sites were determined. Introduction of a methoxy group to indatraline affected its affinity and selectivity greatl y. Except for the 4-methoxy derivative 13a,which had the same high affinity at the dopamine transporter binding site as indatraline, the other methoxy -containing analogues (13b-f and 17) exhibited lower affinity than indatral ine for the three transporter binding sites. However, some of the analogues were more selective than indatraline, and the B-methoxy derivative 13c dis played the highest affinity for both the serotonin and norepinephrine trans porters. This compound retained reasonable affinity for the dopamine transp orter and is a promising template for the development of a long-acting inhi bitor of monoamine transporters. Such inhibitors have potential as medicati ons for treatment, as a substitution medication, or for prevention of the a buse of methamphetamine-like stimulants.