Synthesis, physicochemical and anticonvulsant properties of new N-[(4-arylpiperazin-1-yl)alkyl]-3-phenyl- and 3-(3-methyl-phenyl)-pyrrolidine-2,5-diones.
The series of N-[(4-arylpiperazin-1-yl)-alkyl]-3-phenyl- and 3-(3-methylphenyl)-pyrrolidine-2,5-diones [VIII-XXV] were synthesized and evaluated for anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed in mice, using intraperitoneal (ip) maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole-induced (scPTZ) seizure threshold tests. The neurotoxicity was determined applying the rotorod screen. Compounds VIII-XXV revealed protection only in the electrically induced seizures or were inactive. The most active were Mannich bases of 3-(3-methylphenyl)-pyrrolidine-2,5-dione with electron-withdrawing substituents at position-3 of 4-arylpiperazine fragment [XVII, XVIII], as well as compounds with ethylene or propylene spacer between imide and 4-arylpiperazine nitrogen atoms [XX-XXII, XXV]. All these compounds showed anti-MES protection in mice at doses of 100 mg/kg. Additionally, when given orally, compound XVIII was also active in rats MES screen at a dose of 30 mg/kg.
Obniska
Jolanta
J
Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna St. 30-688 Kraków, Poland. mfobnisk@cyf-kr.edu.pl
Chlebek
Iwona
I
Pichór
Joanna
J
Kopytko
Maciej
M
Kamiński
Krzysztof
K
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000927:Anticonvulsants; D013388:Succinimides