Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3-[4-methylphenyl and 4-chlorophenyl]-2-[5-(substituted phenyl)thiazol-2-yl]tropanes
Synthetic methods were developed for the synthesis of the 3-(4-substituted phenyl)-2-[5-(substituted phenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3-(4-methylphenyl-2-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).