Synthesis and Anticonvulsant Activity of New Calix[4]Arene Derivatives Containing Gamma-Aminobutyric Acid Moieties

摘要

A series of novel mono- and disubstituted p-tert-butylcalix[4]arene derivatives functionalized with gamma-aminobutyric acid (GABA) and its methyl ester were synthesized and screened in vivo for anticonvulsant activity by determining the minimum effective doses of pentylenetetrazole inducing clonic-tonic convulsions and tonic extension. Calixarene derivative X with one acetic acid and one GABA ester on the lower rim of the macrocyclic scaffold was characterized as possessing prolonged anticonvulsant activity. A relationship between the pharmacological effect and the number of amino-acid residues was found. Disubstituted calixarenes IV and IX demonstrated higher anticonvulsant activity 24 h after administration than the monosubstituted analogs.