Synthesis and biological activity of new 6- and 7-substituted 2β- butyl-3-phenyltropanes as ligands for the dopamine transporter

In our search for novel therapeutic agents useful in the treatment of cocaine abuse, we have studied the synthesis and biological activity of 2β- butyl-3-phenyltropane derivatives with the phenyl ring in α- or β- configuration and bearing different substituents at the 6- and 7-positions of the tropane ring. All of the compounds synthesized showed micromolar or submicromolar affinity for the DAT in the rat striatum. In particular, among all the compounds described in this paper, the 7α-fluoro-3α-phenyltropane derivative 12 was found to be the most potent, inhibiting mazindol binding with a K(i) of 0.20 μM and dopamine reuptake with a K(i) of 0.49 μM.