In silico design of novel proton-pump inhibitors with reduced adverse effects / 医学前沿
Frontiers of Medicine
; (4): 277-284, 2019.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-771310
Biblioteca responsável:
WPRO
ABSTRACT
The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features (1) number of ring II = number of ring I + 1; (2) preferably five, six, or seven-membered heteroatomic ring for stability; and (3) 1 < pKa1 < 4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Simulação por Computador
/
Desenho de Fármacos
/
Toxicidade
/
Inibidores da Bomba de Prótons
/
Fenômenos Toxicológicos
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Frontiers of Medicine
Ano de publicação:
2019
Tipo de documento:
Artigo