Spiro[4.5]decane-2-carboxylic acid (12a), spiro[4.5]decane-2,2-dicarboxylic acid (11a), spiro[4.6]undecane-2-carboxylic acid (12b), spiro[4.6]undecane- 2,2-dicarboxylic acid (11b), and spiro[4.6]undecane-2-acetic acid (13) were synthesized by an improved method and evaluated for anticonvulsant activity. These analogues were synthesized to evaluate the role of the carboxylic acid group as an essential substituent in valproic acid (di-n-propylacetic acid, 1). Carbocyclic spiranes are known to resist metabolic alteration so that any activity elicited by these compounds would be due to the carboxylic acid function and not to any metabolic change. Spiro[4.6]undecane-2-carboxylic acid (12b) was the most active analogue tested and the pentylenetetrazol and picrotoxin evaluations of 12b compared favorably to 1. However, 12b failed to provide adequate protection against maximal electroshock seizures, bicuculline, or strychnine in mice. Possible reasons for these results are discussed.

中文翻译：

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螺[4.5]和螺[4.6]羧酸：丙戊酸的环状类似物。合成和抗惊厥评价。

螺[4.5]癸烷-2-羧酸（12a），螺[4.5]癸烷-2,2-二羧酸（11a），螺[4.6]十一烷-2-羧酸（12b），螺[4.6]十一烷-通过改进的方法合成了2，2-二羧酸（11b）和螺[4.6]十一烷-2-乙酸（13），并评估了其抗惊厥活性。合成这些类似物以评估羧酸基团在丙戊酸（二正丙基乙酸，1）中的作用。已知碳环螺烷可抵抗代谢改变，因此这些化合物引起的任何活性将归因于羧酸功能而不是由于任何代谢改变。螺[4.6]十一烷-2-羧酸（12b）是测试过的最活跃的类似物，对12b的戊四氮和微毒素的评价比对1好。但是，12b未能提供足够的保护，以防止小鼠遭受最大的电击惊厥，双小分子碱或士的宁。讨论了导致这些结果的可能原因。