Synthesis and binding affinity of new 1,4-disubstituted triazoles as potential dopamine D3 receptor ligands

Article abstract of DOI:10.1016/j.bmcl.2013.08.047

A series of new 1,4-disubstituted triazoles was prepared from appropriate arylacetylenes and aminoalkylazides using click chemistry methodology. These compounds were evaluated as potential ligands on several subtypes of dopamine receptors in in vitro competition assays, showing high affinity for dopamine D₃ receptors, lower affinity for D₂ and D₄, and no affinity for the D₁ receptors. Compound 18 displayed the highest affinity at the D₃ receptor with a K_i value of 2.7 nM, selectivity over D₂ (70-fold) and D₄ (200-fold), and behaviour as a competitive antagonist in the low nanomolar range.