Synthesis, anticonvulsant properties and 5-HT1A/5-HT2A receptor affinity of new N-[(4-arylpiperazin-1-yl)-propyl]-2-aza-spiro[4.4]nonane and [4.5]decane-1,3-dione derivatives.
作者： Jolanta Obniska , Małgorzata Dybała , Andrzej J Bojarski , Marcin Kołaczkowski , Sijka Charakchieva-Minol
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摘要: A series of twenty new N-[(4-arylpiperazin-1-yl)-propyl]-2-aza-spiro[4.4]nonane- and [4.5]decane-1,3-dione derivatives were synthesized their anticonvulsant activity was evaluated in maximal electroshock (MES) sc pentertazole (sc PTZ) tests. Their neurotoxicity examined as well. Although no antiseizure properties the investigated compounds found MES model, eight them active PTZ test three, namely 2-{3-[4-(2-fluorophenyl)-piperazin-1yl]-propyl}-2-aza-spiro[4.4]nonane-1,3-dione (7), 2-{3-[4-(2-fluorophenyl)-piperazin-1-yl]-propyl}-7-methyl-2-aza-spiro[4.5]-decane-1,3- dione (22) 2-{3-[4-(3-chlorophenyl)-piperazin-1-yl]-propyl}-7-methyl-2-aza-spiro[4.5]-decane-1,3-dione (23) classified to Anticonvulsant Screening Program (ASP) 1 class. In addition, since belong a class long-chain arylpiperazines, serotonin 5-HT1A 5-HT2A receptor affinity determined. All 2-OCH3 3-Cl most potent ligands (Ki = 24-143 70-107 nM, respectively), whereas highest observed for unsubstituted 8-66 nM). No correlation between serotonergic observed.
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