QSAR STUDIES ON THE ANTICONVULSANT ACTIVITY OF 5-SUBSTITUTEDPHENYL-1-HYDRO-AND 1-PROPYL - 3- PYRAZOLIDINONES

The chemical structure and anticonvulsant activity relationship of some 5 - substituted phenyl - 3 - pyrazolidinone derivatives were studied Six pairs (1 - hydro and 1 - propyl substituted) of compounds were designed and synthesized according to the Topliss improved method, and a compound with the highest anticonvulsant activity was found, i. e. 5 - (4-fluorophenyl) - 1 - propyl - 3 - pyrazolidinone, ED₅₀ 14.7 mg/kg (MES Test). QSAR analysis showed that the hydrophobic constant ∑ π greatly influenced their anticonvulsant activity, and the steric parameter (B₄) and electronic parameter (Ⅰ×10²) of the substitutions on the phenyl ring can improve the correlation coefficient (r). Smaller steric volume and more powerful electron withdrawing effect of the substitution on the 5-phenyl ring increased the anticonvulsant activity.