title: Synthesis and binding affinity of new 1,4-disubstituted triazoles as potential dopamine D(3) receptor ligands.
abstract: 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 Ki 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.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Insua
authors.forename: Mario
authors.initials: M
authors.lastname: Alvarado
authors.forename: Christian F
authors.initials: CF
authors.lastname: Masaguer
authors.forename: Alba
authors.initials: A
authors.lastname: Iglesias
authors.forename: José
authors.initials: J
authors.lastname: Brea
authors.forename: María I
authors.initials: MI
authors.lastname: Loza
authors.forename: Laura
authors.initials: L
authors.lastname: Carro
mesh_terms: D057930:Click Chemistry; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D007700:Kinetics; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D014230:Triazoles
keywords: 1,2,3-Triazoles; Binding assays; Click chemistry; Dopamine receptors; Microwaves; Synthesis