Computer-Aided Design and Biological Evaluation of Diazaspirocyclic D4R Antagonists.
ACS Chem Neurosci
; 15(12): 2396-2407, 2024 Jun 19.
Article
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| MEDLINE
| ID: mdl-38847395
ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra, resulting in motor dysfunction. Current treatments are primarily centered around enhancing dopamine signaling or providing dopamine replacement therapy and face limitations such as reduced efficacy over time and adverse side effects. To address these challenges, we identified selective dopamine receptor subtype 4 (D4R) antagonists not previously reported as potential adjuvants for PD management. In this study, a library screening and artificial neural network quantitative structure-activity relationship (QSAR) modeling with experimentally driven library design resulted in a class of spirocyclic compounds to identify candidate D4R antagonists. However, developing selective D4R antagonists suitable for clinical translation remains a challenge.
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MEDLINE
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Diseño Asistido por Computadora
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Relación Estructura-Actividad Cuantitativa
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En
Revista:
ACS Chem Neurosci
Año:
2024
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Article