Cycloalkanoindoles. 1. Syntheses and antiinflammatory actions of some acidic tetrahydrocarbazoles, cyclopentindoles, and cycloheptindoles

Abstract

A novel series of acidic cycloalkanoindoles comprising tetrahydrocarbazole-, cyclopentindole and cycloheptindole-1-acetic acids was 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 established 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 carrageenan in paw edema test. AY-24 873 was about 10 times more active against the chronic than against the acute models of inflammation used.