Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (
6a–
l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (
6m–
x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino] cycloalkanecarboxamides (
3a–
f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed
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Synthesis and anticonvulsant potential of certain new 6-aryl-9-substituted-6,9-diazaspiro[4.5]decane-8,10-diones (
6a–
l) and 1-aryl-4-substituted-1,4-diazaspiro[5.5] undecane-3,5-diones (
6m–
x) are reported. The intermediates 1-[(aryl)(cyanomethyl)amino] cycloalkanecarboxamides (
3a–
f) were prepared via adopting Strecker synthesis on the proper cycloalkanone followed by partial hydrolysis of the obtained nitrile functionality and subsequent
N-cyanomethylation. Compounds
3a–
f were subjected to complete nitrile hydrolysis to give the respective carboxylic acid derivatives
4a–
f which were cyclized under mild conditions to give the spiro compounds
5a–
f. Ultimately, compounds
5a–
f were alkylated or aralkylated to give the target compounds
6a–
i and
6m–
u. On the other hand, compounds
6j–
l and
6v–
x were synthesized from the intermediates
5a–
f through alkylation, dehydration and finally tetrazole ring formation. Anticonvulsant screening of the target compounds
6a–
x revealed that compound
6g showed an ED
50 of 0.0043 mmol/kg in the scPTZ screen, being about 14 and 214 fold more potent than the reference drugs, Phenobarbital (ED
50 = 0.06 mmol/kg) and Ethosuximide (ED
50 = 0.92 mmol/kg), respectively. Compound
6e exhibited an ED
50 of 0.019 mmol/kg, being about 1.8 fold more potent than that of the reference drug, Diphenylhydantoin (ED
50 = 0.034 mmol/kg) in the MES screen. Interestingly, all the test compounds
6a–
x did not show any minimal motor impairment at the maximum administered dose in the neurotoxicity screen.
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