Cycloalkanoindoles. 1. Syntheses and antiinflammatory actions of some acidic tetrahydrocarbazoles, cyclopentindoles, and cycloheptindoles.
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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002227:Carbazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000627:therapeutic use; D003508:Cycloheptanes / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D007211:Indoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000627:therapeutic use; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D002227:Carbazoles; D003508:Cycloheptanes; D003517:Cyclopentanes; D007211:Indoles