title: Synthesis and anticonvulsant activity of new n-mannich bases derived from 5-cyclopropyl-5-phenyl-hydantoins.
abstract: 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 (scPTZ) 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 scPTZ 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.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Byrtus
authors.forename: Jolanta
authors.initials: J
authors.lastname: Obniska
authors.forename: Anna
authors.initials: A
authors.lastname: Czopek
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kamiński
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D006827:Hydantoins / Q000737:chemistry*; D008297:Male; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D015394:Molecular Structure; D020258:Neurotoxicity Syndromes / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D006827:Hydantoins; D008352:Mannich Bases