Computer-Aided Design and Biological Evaluation of Diazaspirocyclic D4R Antagonists.
ACS Chem Neurosci
; 15(12): 2396-2407, 2024 Jun 19.
Article
em En
| 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho Assistido por Computador
/
Relação Quantitativa Estrutura-Atividade
Limite:
Animals
/
Humans
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos