Anticonvulsant properties of N-(4-methylpiperazin-1-yl)- and N-[3-(4-methyl-piperazin-1-yl)propyl] derivatives of 3-aryl- and 3-spirocycloalkyl-pyrrolidine-2,5-dione.
Two series of N-(4-methylpiperazin-1-yl)- and N-[3-(4-methylpiperazin-1-yl)-propyl]-3-aryl- and 3-spirocycloalkyl-pyrrolidine-2,5-dione derivatives were synthesized and tested for anticonvulsant activity in the maximum electroshock (MES) seizure and pentetrazole (sc PTZ) seizure threshold tests. Compounds with an aromatic ring at position-3 of pyrrolidine-2,5-dione exhibited anticonvulsant activity in the MES test. For that series of compounds, ED50 values were determined. The most potent in the series were derivatives and with a chlorine atom at position-3 or 4 of the aromatic ring. Those compounds exhibited strong anticonvulsant activity, and their ED50 values ranged from 29 to 48 mg/kg. Introduction of the spirocycloalkyl ring into the position-3 of pyrrolidine-2,5-dione made those compounds inactive.
Obniska
Jolanta
J
Department of Pharmaceutical Chemistry, Collegium Medicum of the Jagiellonian University, Medyczna 9, PL 30-688 Kraków, Poland.
Jurczyk
Sławomir
S
Zejc
Alfred
A
Kamiński
Krzysztof
K
Tatarczyńska
Ewa
E
Stachowicz
Katarzyna
K
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D004597:Electroshock; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy; D013141:Spiro Compounds / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D010879:Piperazines; D011759:Pyrrolidines; D013141:Spiro Compounds