Design, Synthesis, and Structure-Activity Relationship Analysis of Thiazolo[3,2-a]pyrimidine Derivatives with Anti-inflammatory Activity in Acute Lung Injury.
ChemMedChem
; 12(13): 1022-1032, 2017 07 06.
Article
em En
| MEDLINE
| ID: mdl-28503918
ABSTRACT
Acute lung injury (ALI) has a high lethality rate, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contribute most to tissue deterioration in cases of ALI. In this study, we designed and synthesized a new series of thiazolo[3,2-a]pyrimidine derivatives based on a previously identified lead compound, and we evaluated their anti-inflammatory activities. Structure-activity relationship studies led to the discovery of two highly potent inhibitors. The two promising compounds were found to inhibit lipopolysaccharide (LPS)-induced IL-6 and TNF-α release in a dose-dependent manner in mouse primary peritoneal macrophages (MPMs). Furthermore, administration of these compounds resulted in lung histopathological improvements and attenuated LPS-induced ALI inâ
vivo. Taken together, these data indicate that these novel thiazolo[3,2-a]pyrimidine derivatives could be developed as candidate drugs for the treatment of ALI.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Tiazóis
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Anti-Inflamatórios não Esteroides
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Lesão Pulmonar Aguda
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article