High dopamine transporter selectivity can be displayed by remarkably simple non-nitrogen containing inhibitors

A series of 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid esters and amides were prepared and tested for binding to the DAT, SERT, and NET. The achiral compounds were easily attained and found to inhibit DAT binding with Ki-values ranging from 0.095 to 0.00003 mM. Among the compounds tested 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid 2-methylphenyl ester was found to be highly selective with SERT/DAT > 7000; NET/DAT > 1700, Ki = 60 nM.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide