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SCIENTIFIC LITERATURE · MED

Computer-Aided Design and Biological Evaluation of Diazaspirocyclic D<sub>4</sub>R Antagonists.

ACS Chem Neurosci · 2024-06-07

DOI: 10.1021/acschemneuro.4c00086PMID: 38847395

Check source for accessResearch Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., ExtramuralOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

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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