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Search for New Anticonvulsant Compounds, Part 2. Structure‐Activity Relationship Studies of New N ‐Substituted Amides of α‐Piperazine‐γ‐Hydroxybutyric Acid as Active Anticonvulsants
Author(s) -
Malawska Barbara,
Kulig Katarzyna,
CiechanowiczRutkowska Maria
Publication year - 1997
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.19973300403
Subject(s) - chemistry , piperazine , anticonvulsant , benzylamine , aminolysis , stereochemistry , tetrahydrofuran , medicinal chemistry , organic chemistry , neuroscience , solvent , epilepsy , biology , catalysis
In a search for new anticonvulsants, two series of compounds, viz. derivatives of N ‐benzylamides of α‐(4‐phenylpiperazine)‐γ‐hydroxybutyric acid ( A and derivatives of N ‐benzylamides of α‐(4‐benzylpiperazine)‐γ‐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 .