Novel spirohydantoin derivative as a potent multireceptor-active antipsychotic and antidepressant agent.
Basic Information
ID: ALA3588770
Journal: Bioorg Med Chem
Title: Novel spirohydantoin derivative as a potent multireceptor-active antipsychotic and antidepressant agent.
Authors: Czopek A, Kołaczkowski M, Bucki A, Byrtus H, Pawłowski M, Kazek G, Bojarski AJ, Piaskowska A, Kalinowska-Tłuścik J, Partyka A, Wesołowska A.
Abstract: A series of novel spirohydantoin derivatives with arylpiperazinylbutyl moiety were synthesized and evaluated for serotonin 5-HT1A, 5-HT2A, 5-HT7 and dopamine D2 receptors. Based on these data, four compounds were selected for further binding affinity assays on dopamine D1, D3, D4, and 5-HT2C, 5-HT6 as well as adrenergic α1 and α2C receptors, which are involved in various CNS diseases such as schizophrenia, anxiety and/or depression. The compound 14, 1-{4-[4-(2-metoxyphe-nyl)piperazin-1-yl]butyl}-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, with the most promising functional profile, mixed 5-HT2A/D2 antagonist and 5-HT1A partial agonist, was selected. In the mouse d-amphetamine-induced locomotor hyperactivity model, compound 14 produced antipsychotic-like activity, which is devoid of cataleptogenic effects and in the forced swim test in mice, it showed a significant antidepressant-like effect unlike the reference drug aripiprazole.
CiteXplore: 25936259
DOI: 10.1016/j.bmc.2015.04.026
Patent ID: ┄