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- Title
Impact of N-Alkylamino Substituents on Serotonin Receptor (5-HTR) Affinity and Phosphodiesterase 10A (PDE10A) Inhibition of Isoindole-1,3-dione Derivatives.
- Authors
Czopek, Anna; Partyka, Anna; Bucki, Adam; Pawłowski, Maciej; Kołaczkowski, Marcin; Siwek, Agata; Głuch-Lutwin, Monika; Koczurkiewicz, Paulina; Pękala, Elżbieta; Jaromin, Anna; Tyliszczak, Bożena; Wesołowska, Anna; Zagórska, Agnieszka; Jampilek, Josef
- Abstract
In this study, a series of compounds derived from 4-methoxy-1H-isoindole-1,3(2H)-dione, potential ligands of phosphodiesterase 10A and serotonin receptors, were investigated as potential antipsychotics. A library of 4-methoxy-1H-isoindole-1,3(2H)-dione derivatives with various amine moieties was synthesized and examined for their phosphodiesterase 10A (PDE10A)-inhibiting properties and their 5-HT1A and 5-HT7 receptor affinities. Based on in vitro studies, the most potent compound, 18 (2-[4-(1H-benzimidazol-2-yl)butyl]-4-methoxy-1H-isoindole-1,3(2H)-dione), was selected and its safety in vitro was evaluated. In order to explain the binding mode of compound 18 in the active site of the PDE10A enzyme and describe the molecular interactions responsible for its inhibition, computer-aided docking studies were performed. The potential antipsychotic properties of compound 18 in a behavioral model of schizophrenia were also investigated.
- Subjects
SEROTONIN receptors; BINDING sites; MOLECULAR interactions; HUMAN behavior models; MOIETIES (Chemistry)
- Publication
Molecules, 2020, Vol 25, Issue 17, p3868
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25173868