Design and synthesis of novel pyrazolo[4,3-d]pyrimidines as potential therapeutic agents for acute lung injury.
J Enzyme Inhib Med Chem
; 34(1): 1121-1130, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31117832
ABSTRACT
Four series of total 35 new pyrazolo[4,3-d]pyrimidine compounds were designed, synthesized and evaluated for their inhibitory activity against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 4e was found to be the most potent inhibitor, which decreased the production of cytokines in vitro, such as NO, IL-6 and TNF-α, with IC50 values of 2.64, 4.38 and 5.63 µM, respectively. Further studies showed that compound 4e inhibited cytokines secretion of macrophages through suppressing TLR4/p38 signaling pathway. Additionally, compound 4e showed in vivo anti-inflammatory activity in LPS-induced model of acute lung injury. These data suggested that compound 4e may be a promising lead structure for the treatment of ALI.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Pirimidinas
/
Diseño de Fármacos
/
Lesión Pulmonar Aguda
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article