Discovery of novel dual PPARα/δ agonists based on benzimidazole scaffold for the treatment of non-alcoholic fatty liver disease.
Bioorg Chem
; 99: 103803, 2020 06.
Article
in En
| MEDLINE
| ID: mdl-32251945
ABSTRACT
Many peroxisome proliferator-activated receptors (PPARs) agonists have been developed for the treatment of metabolic disorders, while several PPARs agonists were discontinued in clinical trials because of PPARγ related side effects. In order to increase the selectivity against PPARγ, we performed a structure-activity relationship study based on PPARα/γ/δ agonist MHY2013. These efforts eventually led to the identification of compound 4, a dual PPARα/δ agonist with considerable potencies on PPARα/δ and high selectivity against PPARγ. In the Western Diet and CCl4-induced non-alcoholic steatohepatitis model, compound 4 alleviates the hepatic steatosis, inflammation, and fibrosis. These results indicated that dual PPARα/δ agonist 4 might be a promising lead compound for further investigations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzimidazoles
/
PPAR alpha
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PPAR gamma
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Drug Discovery
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Fatty Liver
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Non-alcoholic Fatty Liver Disease
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Bioorg Chem
Year:
2020
Type:
Article