Synthesis and Pharmacological Evaluation of New 34-Dihydroisoquinolin Derivatives Containing Heterocycle as Potential Anticonvulsant Agents

摘要

Two novel series of 3,4-dihydroisoquinolin with heterocycle derivatives (>4a–>t and >9a–>e) were synthesized and evaluated for their anticonvulsant activity using maximal electroshock (MES) test and pentylenetetrazole (PTZ)-induced seizure test. All compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and mass spectral data. Among them, 9-(exyloxy)-5,6-dihydro-[1,2,4]triazolo[3,4-a]isoquinolin-3(2H)-one (>9a) showed significant anticonvulsant activity in MES tests with an ED50 value of 63.31 mg/kg and it showed wide margins of safety with protective index (PI > 7.9). It showed much higher anticonvulsant activity than that of valproate. It also demonstrated potent activity against PTZ-induced seizures. A docking study of compound >9a in the benzodiazepine (BZD)-binding site of γ-aminobutyric acidA (GABAA) receptor confirmed possible binding of compound >9a with the BZD receptors.