Abstract
A series of stiripentol (STP) analogues namely, 2-[(1
E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ylidene]-
N-(aryl/
H)hydrazinecarboxamides
7a–
h, (±)-(5RS)-
N-(aryl/
H)-(1,3-benzodioxol-5-yl)-3-
tert-butyl-4,5-dihydro-1
H-pyrazole-1-carboxamides (±)-
8a–
h, and (±)
-[(5
RS)-(1,3-benzodioxol-5-yl)-3-
tert-butyl-4,5-dihydro-1
H-pyrazol-1-yl](aryl)methanones (±)-
13a–
f was synthesized by adopting appropriate synthetic routes and was pharmacologically evaluated in the preliminary anticonvulsant screens. The selected bioactive new chemical entities were subjected to ED
50 determination and neurotoxicity evaluation. The most active congeners are
7h in MES screen and (±)-
13b in scPTZ screen which displayed ED
50 values of 87 and 110 mg/kg, respectively, as compared to that of STP (ED
50 = 277.7 and 115 mg/kg in MES and scPTZ, respectively).
The synthesis and anticonvulsant activity of certain novel stiripentol analogues
7a–
h, (±)
8a–
h, and (±)
13a–
f are reported. The anticonvulsant potential of the prepared compounds was evaluated using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock seizures (MES) screens.
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► Synthesis of novel analogues of stiripentol (STP) as anticonvulsants. ► Compound
13b is the most promising new bioactive chemical entity. ►
13b displayed ED
50 of 110 (93.19–129.85) mg/kg in scPTZ anticonvulsant test.