[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 sigma pi greatly influenced their anticonvulsant activity, and the steric parameter (B4) and electronic parameter (I x 10(2] 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.
Lei
X P
XP
Beijing Medical University.
Luan
Y
Y
Ling
Y Z
YZ
Li
R L
RL
Pei
Y Q
YQ
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D011720:Pyrazoles; C068773:5-(4-fluorophenyl)-1-propyl-3-pyrazolidinone