STUDY OF THE RELATIONSHIP BETWEEN STRUCTURE AND ANTICONVULSANT ACTIVITIES OF 1-SUBSTITUTED 3-PYRAZOLIDINONES

In order to study the relationship between chemical structure and anticonvulsant activities of the GABA-T inhibitor, a series of 1-substituted 3-pyrazolidinones were synthesized. By using the Fibonacci Search Method, six 3-pyrazolidinones with straight chain alkyl substituents on 1-position were synthesized. Their anticonvulsant activities shoved that the most suitable chains were decyl and dodecyl groups. QSAR studies by stepwise regression analysis showed that the activities of the nine 1-substituted 3-pyrazolidinones were parabolically related to the values of the alkyl substiluents, The equation demonstrated that the most suitable chain was decyl group. The predicate activity values of 1-chloroethyl, 1-(p-chlorobenzyl-)and non-substitiuted compound coincided with the experimental facts. Pharmacologic experiments showed that some of the compounds can increase the GABA. level in the brain of mice significantly.