Design and synthesis of a second series of triazole-based compounds as potent dual mPGES-1 and 5-lipoxygenase inhibitors.
Eur J Med Chem
; 54: 311-23, 2012 Aug.
Article
en En
| MEDLINE
| ID: mdl-22683242
ABSTRACT
Microsomal prostaglandin E(2) synthase (mPGES)-1 and 5-lipoxygenase (5-LO) are pivotal enzymes in the biosynthesis of the pro-inflammatory PGE(2) and leukotrienes, respectively. The design and synthesis of a second series of mPGES-1 inhibitors based on a triazole scaffold are described. Our studies allowed us to draw a tentative SAR profile and to optimize this series with the identification of compounds 10, 11 and 14-15 which displayed potent mPGES-1 inhibition in a cell-free assay. In addition, compounds 5, 10, 12 and 14-16 also blocked 5-LO activity in cell-free and cell-based test systems, emerging as very promising candidates for the development of safer and more effective anti-inflammatory drugs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triazoles
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Araquidonato 5-Lipooxigenasa
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Diseño de Fármacos
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Inhibidores de la Lipooxigenasa
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Oxidorreductasas Intramoleculares
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2012
Tipo del documento:
Article
País de afiliación:
Italia