Synthesis and anticonvulsant properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane, 2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine-2,5-dione. Part IV.
To continue our systematic SAR studies a series of N-phenylamino derivatives of 2-azaspiro[4.4]nonane-, 2-azaspiro[4.5]decane-, 6-methyl-2-azaspiro[4.5]decane-1,3-dione and 3-cyclohexylpyrrolidine-2,5-dione were synthesized and tested for their anticonvulsant activity in the maximum electroshock seizure (MES) and subcutaneous metrazole seizure threshold (sc. Met) tests. Among those molecules the most potent were N-(4-methylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [V], N-(2-trifluoromethylphenyl)-amino-2-azaspiro[4.4]nonane-1,3-dione [VI], N-(3-methylphenyl)-amino-2-azaspiro[4.5]decane-1,3-dione [VIII] and N-(4-methylphenyl)-amino-6-methyl-2-azaspiro[4.5]decane-1,3-dione [XIV], which inhibited the seizures mainly in the sc. Met test. The obtained results revealed that anticonvulsant activity depended on the presence and the position of the methyl or trifluoromethyl groups at the aryl moiety, as well as the size and the manner of attachment of the cycloalkyl system at the position-3 of the pyrrolidine-2,5-dione ring.
Obniska
Jolanta
J
Department of Pharmaceutical Chemistry, Medical College of the Jagiellonian University, 9 Medyczna Str., 30-688 Kraków, Poland.
Kamiński
Krzysztof
K
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D051379:Mice; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000927:Anticonvulsants; D001372:Aza Compounds; D003510:Cyclohexanes; D013141:Spiro Compounds; D013388:Succinimides