Design, synthesis, and biological evaluation of piperazine derivatives as pan-PPARs agonists for the treatment of liver fibrosis.
Eur J Med Chem
; 269: 116344, 2024 Apr 05.
Article
em En
| MEDLINE
| ID: mdl-38522113
ABSTRACT
Liver fibrosis is commonly occurred in chronic liver diseases, but there is no approved drug for clinical use. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) could not only regulate metabolic homeostasis but also possess anti-inflammatory and antifibrotic effects, and pan-PPARs agonist was considered as a potential anti-liver fibrosis agent. In this study, a series of novel piperazine pan-PPARs agonists were developed, and the preferred compound 12 displayed potent and well-balanced pan-PPARs agonistic activity. Moreover, compound 12 could dose-dependently stimulate the PPARs target genes expression and showed high selectivity over other related nuclear receptors. Importantly, compound 12 exhibited excellent pharmacokinetic profiles and good anti-liver fibrosis effects in vivo. Collectively, compound 12 holds promise for developing an anti-liver fibrosis agent.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Ativados por Proliferador de Peroxissomo
/
Compostos Heterocíclicos
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
/
Eur. j. med. chem
/
European journal of medicinal chemistry
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China