Asselin A A, Humber L G, Dobson T A, Komlossy J
J Med Chem. 1976 Jun;19(6):787-92. doi: 10.1021/jm00228a010.
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.
通过苯肼与1-烷基-2-氧代环烷酸酯之间的费歇尔吲哚合成法，合成了一系列新型酸性环烷吲哚，包括四氢咔唑-、环戊吲哚-和环庚吲哚-1-乙酸。对这些化合物进行了口服评估，以确定它们降低大鼠佐剂性关节炎的能力。该系列中活性最高的化合物是1-乙基-8-正丙基-1,2,3,4-四氢咔唑-1-乙酸（AY-24 873），其半数有效剂量为1.1±0.2mg/kg。还在大鼠中口服研究了AY-24 873对角叉菜胶足爪水肿试验中急性炎症反应的影响。结果发现，AY-24 873对慢性炎症模型的活性比对急性炎症模型的活性高约十倍。
