A new class of anticonvulsants possessing 6 Hz activity: 3,4-dialkyloxy thiophene bishydrazones.

Abstract

Thirty nine new 3,4-di(substituted)oxy-N(2),N(5)-bis(substituted)thiophene-2,5-dicarbohydrazides were synthesized starting from ethyl thiodiglycolate through multi-step reactions. In the synthetic sequence, 3,4-dihydroxythiophene-2,5-diester (1) was obtained by condensing the ethyl thiodiglycolate with diethyl oxalate. It was derivatized using different alkyl halides to give disubstituted thiophene esters (2-5), which were then converted to corresponding hydrazides (6-9) following usual methods. Finally, these hydrazides, on treatment with various substituted carbonyl compounds underwent smooth condensation to yield target hydrazones (10-13). The new compounds were characterized using FT-IR, (1)H NMR and (13)C NMR, mass spectral and elemental analyses. The anticonvulsant activity of the title compounds was established after intraperitoneal (ip) administration in three seizure models, which include maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and 6 Hz screens and their neurotoxicity was also evaluated. Compound 11f has emerged as an active compound with no neurotoxicity in this series. Also, the structure-activity relationship of the tested compounds was discussed.

• Authors: Ravi Kulandasamy, Airody Vasudeva Adhikari, James P Stables
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 44 Issue 11 Pg. 4376-84 (Nov 2009) ISSN: 1768-3254 [Electronic] France
• PMID: 19556038 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Hydrazones
• Thiophenes
• Pentylenetetrazole

Topics

• Animals
• Anticonvulsants (adverse effects, chemistry, therapeutic use)
• Electroshock
• Hydrazones (adverse effects, chemistry, therapeutic use)
• Male
• Mice
• Molecular Structure
• Motor Activity (drug effects)
• Pentylenetetrazole
• Seizures (chemically induced, drug therapy)
• Structure-Activity Relationship
• Thiophenes (adverse effects, chemistry, therapeutic use)