RESUMEN

The compound 1-(2,6-dichlorophenyl)indolin-2-one (1), planned as a pro-drug of diclofenac (2), was easily synthesized in 94% yield by an intramolecular reaction in the presence of coupling agent (i.e., EDC). Compound 1 showed anti-inflammatory and analgesic activity without gastro-ulcerogenic effects. The chemical and enzymatic hydrolysis profile of the lactam derivative 1 does not indicate conversion to diclofenac (2). This compound is a new non-ulcerogenic prototype for treatment of chronic inflammatory diseases.

Asunto(s)

Antiinflamatorios/efectos adversos , Antiinflamatorios/síntesis química , Diseño de Fármacos , Indoles/síntesis química , Indoles/farmacología , Úlcera Gástrica/inducido químicamente , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Carragenina , Celecoxib , Diclofenaco/efectos adversos , Diclofenaco/química , Diclofenaco/farmacología , Hidrólisis/efectos de los fármacos , Indoles/química , Lactamas/sangre , Lactamas/química , Masculino , Modelos Moleculares , Pirazoles/efectos adversos , Pirazoles/farmacología , Ratas , Ratas Wistar , Sulfonamidas/efectos adversos , Sulfonamidas/farmacología