Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors.
Bioorg Med Chem Lett
; 22(14): 4769-72, 2012 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-22677317
ABSTRACT
Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro-pyrazolo[1,2-a]pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Acetil-CoA Carboxilasa
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Pirazoles
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Compuestos de Espiro
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Inhibidores Enzimáticos
Límite:
Animals
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Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article