title: Search for New Anticonvulsant Compounds, Part 2. Structure-activity relationship studies of new N-substituted amides of alpha-piperazine-gamma-hydroxybutyric acid as active anticonvulsants.
abstract: In a search for new anticonvulsants, two series of compounds, viz. derivatives of N-benzylamides of alpha-(4-phenylpiperazine)-gamma-hydroxybutyric acid (A) and derivatives of N-benzylamides of alpha-(4-benzylpiperazine)-gamma-hydroxybutyric acid (B), were investigated. These amides were obtained by aminolysis of 3-(4-phenyl-, or 4-benzylpiperazine)-tetrahydrofuran-2-one with primary arylalkylamines (i.e. 2-phenylethylamine and 2,3,4-substituted derivatives of benzylamine). Preliminary pharmacological tests, a maximal electroshock (MES) and a subcutaneous metrazole (scMet), and a rotorod toxicity assay were employed. All compounds displayed anticonvulsant activity at range of doses 100-300 mg/kg in the MES screens. In order to point to some structural features correlating with the MES anticonvulsant activity crystal structure analysis followed by conformational analysis was carried out on two representative compounds of series A and B.
authors.affiliation: Department of Pharmaceutical Chemistry, Collegium Medicum of Jagiellonian University, Kraków, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Malawska
authors.forename: K
authors.initials: K
authors.lastname: Kulig
authors.forename: M
authors.initials: M
authors.lastname: Ciechanowicz-Rutkowska
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D010879:Piperazines; D010433:Pentylenetetrazole