Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Design and Synthesis of New Amides and Thioamides Derived from 3,4-Ethylenedioxythiophene as Potential Anticonvulsants

  • Kulandasamy, Ravi (Department of Chemistry, National Institute of Technology Karnataka) ;
  • Adhikari, Airody Vasudeva (Department of Chemistry, National Institute of Technology Karnataka) ;
  • Stables, James P. (Preclinical Pharmacology Section, Epilepsy Branch, National Institute of Health)
  • Received : 2010.05.10
  • Accepted : 2010.09.15
  • Published : 2010.11.20
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Abstract

Five new series of 3,4-ethylenedioxythiophene derivatives carrying important pharamacophores, viz., amide, ester, ether and active secondary aryl moieties have been designed and synthesized through multistep reactions starting from thiodiglycolic ester and diethyl oxalate. They have been characterized by elemental and spectral data. All the target compounds have been screened for their anticonvulsant activity at three different models viz. maximal electroshock (MES), subcutaneous metrazole (scMET), and 6 Hz screen and evaluated for their neurotoxicity in rotorod model. Compound 6a emerged as lead with no neurotoxicity. All the five series of compounds are safe in the toxicity studies at the maximum dose of 300 mg/kg of body weight. Amongst the tested compounds, the ester pharmacophore with thioamide fragment has showed better activity than the other analogs.

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