RESUMEN
A novel series of acidic cycloalkanoindoles comprising tetrahydrocarbazole-, cyclopentindole-, and cycloheptindole-1-acetic acids has been synthesized via the Fischer indolization between a phenylhydrazine and a 1-alkyl-2-oxocycloalkaneacetic acid ester. These compounds were evaluated, orally, for their capacities to decrease estabished adjuvant arthritis in rats. The most active compound of the series was 1-ethyl-8-n-propyl-1,2,3,4-tetrahydrocarbazole-1-acetic acid (AY-24 873),which had an ED50 of 1.1 +/- 0.2 mg/kg. AY-24 873 was also studied orally in rats for its effect on the acute inflammatory response in the carrageenin paw edema test. It was found that AY-24 873 was about ten times more active against the chromic than against the acute models of inflammation used.
Asunto(s)
Antiinflamatorios/síntesis química , Carbazoles/síntesis química , Indoles/síntesis química , Animales , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Carbazoles/efectos adversos , Carbazoles/uso terapéutico , Cicloheptanos/efectos adversos , Cicloheptanos/síntesis química , Cicloheptanos/uso terapéutico , Ciclopentanos/síntesis química , Ciclopentanos/uso terapéutico , Edema/tratamiento farmacológico , Indoles/efectos adversos , Indoles/uso terapéutico , Ratas , Úlcera Gástrica/inducido químicamente , Relación Estructura-ActividadRESUMEN
The synthesis and antiinflammatory activities of a series of 23 novel 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-alkanoic acids are described and some relationships between structure and activity are discussed. One of these compounds, 1,3,4,9-tetrahydro-1-propylpyrano[3,4-b]indole-1-acetic acid (prodolic acid, USAN), has been selected for further studies.
