Synthesis and biological evaluation of 5-[[3,5-bis(1,1-dimethylethyl)- 4-hydroxyphenyl]methylene]oxazoles, -thiazoles, and -imidazoles: novel dual 5-lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity.
J Med Chem
; 37(2): 322-8, 1994 Jan 21.
Article
en En
| MEDLINE
| ID: mdl-8295221
A variety of benzylideneoxazoles, -thiazoles, and -imidazoles derived from 2,6-di-tert-butylphenol were prepared and evaluated as dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. The target compounds exhibit varying degrees of selectivity toward the two enzymes. Several compounds are orally active in the rat carageenan footpad edema (CFE) and mycobacterium footpad edema (MFE) antiinflammatory models. Structure-activity relationships are discussed. From this work, (Z)-5-[[3,5-bis(1,1-dimethylethyl)-4- hydroxyphenyl]-methylene]-2-imino-4-thiazolidinone methanesulfonate salt (CI-1004) was identified as a potent dual inhibitor of 5-lipoxygenase (IC50 = 0.77 microM) and cyclooxygenase (IC50 = 0.39 microM), with oral activity (ID40 = 0.6 mg/kg) in the rat MFE model of inflammation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxazoles
/
Tiazoles
/
Antiinflamatorios no Esteroideos
/
Inhibidores de la Lipooxigenasa
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Inhibidores de la Ciclooxigenasa
/
Imidazoles
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1994
Tipo del documento:
Article
Pais de publicación:
Estados Unidos