A series of N-phenyl- and N-benzyl-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-diones containing a fluoro or trifluoromethyl substituents at the aryl ring was synthesized and tested for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous metrazole (sc.Met) tests. Among them, the most active were N-benzyl derivatives with fluoro and trifluoromethyl substituents especially at position-2 of the aryl moiety. The introduction of the phenyl ring at the imide nitrogen atom resulted in less active compounds. The results obtained showed that incorporation of fluoro or trifluoromethyl substituents increased the anticonvulsant activity in comparison to respective chloro, methoxy or methyl analogues. Crystallographically obtained conformation for one active and two inactive derivatives with trifluoromethyl substituents at position-2 or -3 of phenyl ring were initially used for molecular electrostatic potentials (MEP) calculation. The MEP distribution at carbonyl oxygen atoms was different for active and inactive molecules.

中文翻译：

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新型氟化N-苯基-和N-苄基-2-氮杂螺[4.4]壬烷-和[4.5]癸烷-1,3-二酮衍生物的合成和抗惊厥活性：第三部分

合成了一系列在芳基环上含有氟或三氟甲基取代基的N-苯基-和N-苄基-2-氮杂螺[4.4]壬烷-和[4.5]癸烷-1,3-二酮，并测试了它们的抗惊厥活性。最大电击（MES）和皮下甲拉唑（sc.Met）测试。其中，最活跃的是N具有氟和三氟甲基取代基的-苄基衍生物，特别是在芳基部分的2位上。在酰亚胺氮原子上引入苯环会导致活性较低的化合物。获得的结果表明，与相应的氯，甲氧基或甲基类似物相比，氟或三氟甲基取代基的掺入提高了抗惊厥活性。晶体学上获得的一种活性和两种非活性衍生物在苯环的2位或-3位具有三氟甲基取代基的构象最初用于分子静电势（MEP）计算。对于活性和非活性分子，羰基氧原子上的MEP分布是不同的。