Synthesis and anticonvulsant activity of some new proline-benzofuran-acetamide/propanamide/butanamide hybrids

Six new proline-benzofuran-acetamide/propanamide/butanamide hybrids (6a-b, 7a-b, 8a-b) were synthesized. The structures of the synthesized compounds were confirmed on the basis of their elemental analyses and spectral characterization. The anticonvulsant screening was determined using the two classical animal models, namely, maximal electroshock seizure (MES) and subcutaneous metrazol (scMET) models followed by motor impairment study by rotarod test in mice. Compounds 6b, 7b, 8a, and 8b showed potent anticonvulsant activity in MES model with median effective dose (ED₅₀) of 65.3 mg/kg, 36.5 mg/kg, 56.7 mg/kg, and 31.6 mg/kg, respectively. Compounds 7b (100 mg/kg, 0.5 h; 300 mg/kg, 4 h) and 8b (100 mg/kg, 0.5 h and 4 h) also showed significant anticonvulsant activity against scMET test.