Synthesis and anticonvulsant activity of some new bishydrazones derived from 3,4-dipropyloxythiophene

A series of new 3,4-dipropyloxy-N2,N5-bis(substituted)thiophene-2,5-dicarbohydrazides (4–30) were synthesized from ethyl thiodiglycolate and diethyloxalate through multistep reactions. Following Dieckmann–Komppa reaction, the required precursor 3,4-dihydroxythiophene-2,5-diester (1) was prepared. This was derivatized with propyl bromide and further converted to corresponding hydrazide (3), which was finally transformed to targeted hydrazones (4–30) by conventional methods. The newly synthesized compounds were characterized using FT-IR, 1H and 13C NMR, EI-MS and elemental analyses. The anticonvulsant activity of all the title compounds was investigated against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scMET) models and their neurotoxicity was also evaluated. Some of the selected compounds were subjected to 6 Hz test in order to evaluate their uncover activities. Compound 3,4-dipropyloxy-N2,N5-bis[1-(2-thienyl)ethylidene]thiophene-2,5-dicarbohydrazide (15) has emerged as a lead in this series with less neurotoxicity.

Graphical abstractTwenty-seven new 3,4-dipropyloxy-N2,N5-bis(substituted)thiophene-2,5-dicarbohydrazides (4–30) were synthesized and screened for their anticonvulsant activity and neurotoxicity. MES, scMET and 6 Hz models were followed for investigation of their antiepileptic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide