title: Parallel synthesis of potent dopaminergic N-phenyltriazole carboxamides applying a novel click chemistry based phenol linker.
abstract: Taking advantage of our click chemistry based methodology to construct novel SPOS (solid phase organic synthesis) resins, the triazolylmethyl linked catechol 6a was discovered, which is readily available via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of azidomethyl substituted polystyrene with O-propargylcatechol and can be applied for the parallel synthesis of N-phenyltriazole carboxamides. As a proof-of-concept, a 'catch-and-release' strategy could be successfully applied for a parallel synthesis of dopaminergic phenyltriazoles of type 2. A focused model library of 20 test compounds revealing three points of diversity was generated by a three-step SPOS approach. Product purification was performed employing a solid-supported carboxylic acid anhydride as a scavenger. GPCR-ligand binding screening revealed dopamine D3 receptor ligands with K(i) values in the single digit nanomolar range.
authors: Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
authors: Pilar Rodriguez
authors: PR
authors: Loaiza
authors: Stefan
authors: S
authors: Löber
authors: Harald
authors: H
authors: Hübner
authors: Peter
authors: P
authors: Gmeiner
mesh_terms: D018663:Adrenergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry; D011485:Protein Binding; D011954:Receptors, Dopamine / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D013552:Swine; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D018663:Adrenergic Agents; D008024:Ligands; D010636:Phenols; D011954:Receptors, Dopamine; D050637:Receptors, Dopamine D3; D014230:Triazoles