title: Parallel synthesis and biological screening of dopamine receptor ligands taking advantage of a click chemistry based BAL linker.
abstract: The click-chemistry-derived formyl indolyl methyl triazole (FIMT) resin 1a was evaluated for the parallel solid-phase synthesis of a series of BP-897-type arylcarboxamides. By application of a five-step sequence (including loading by reductive amination, subsequent amide coupling, deprotection, palladium-catalyzed N-arylation, and acidic cleavage), a focused library of putative dopamine D3 receptor ligands was constructed. The final products revealed good to excellent purity and were screened for binding at monoaminergic G-protein-coupled receptors when selected library members proved to show excellent binding affinity, especially toward the dopamine D3 receptor subtype.
authors.affiliation: Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052, Erlangen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Bettinetti
authors.forename: Stefan
authors.initials: S
authors.lastname: Löber
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
mesh_terms: D000577:Amides / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008024:Ligands; D011869:Radioligand Assay; D050637:Receptors, Dopamine D3 / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D008024:Ligands; D050637:Receptors, Dopamine D3