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Synthesis and Anticonvulsant Activity of New N ‐Mannich Bases Derived from 5‐Cyclopropyl‐5‐phenyl‐hydantoins
Author(s) -
Byrtus Hanna,
Obniska Jolanta,
Czopek Anna,
Kamiński Krzysztof
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201000241
Subject(s) - anticonvulsant , phenytoin , ethosuximide , chemistry , pharmacology , neurotoxicity , stereochemistry , epilepsy , toxicity , medicine , organic chemistry , psychiatry
Synthesis, physicochemical and anticonvulsant properties of new N ‐Mannich bases 3–24 derived from 5‐cyclopropyl‐5‐phenyl‐ and 5‐cyclopropyl‐5‐(4‐chlorophenyl)‐hydantoins were described here. Initial anticonvulsant screening was performed using intraperitoneal ( i.p. ) maximal electroshock (MES) and subcutaneous pentylenetetrazole ( sc PTZ) seizures tests. Selected derivatives were also screened in the 6‐Hz test. The neurotoxicity was determined applying the rotorod test. The pharmacological results revealed that the majority of compounds were effective in MES and/or sc PTZ tests. The quantitative studies after oral administration into rats showed that several molecules were more potent than phenytoin and ethosuximide which were used as reference antiepileptic drugs. From the whole series the most active was 3‐[(4‐phenylpiperazin‐1‐yl)‐methyl]‐5‐cyclopropyl‐5‐phenyl‐imidazolidine‐2,4‐dione ( 3 ) with the ED 50 value of 5.29 mg/kg in the MES test.