Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: one more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4168-72. doi: 10.1016/j.bmcl.2010.05.059. Epub 2010 May 20.

Abstract

A series of novel N(1)-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N(4)-(4-substitutedbenzaldehyde)-semicarbazone, N(1)-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N(4)-[1-(4-substitutedphenyl)ethanone]-semicarbazone and N(1)-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N(4)-[1-(4-substitutedphenyl) (phenyl) methanone]-semicarbazone were designed and synthesized on the basis of semicarbazone based pharmacophoric model to meet the structural requirements necessary for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The efforts were also made to establish structure activity relationships among synthesized compounds. The results of the present studying validated that the pharmacophoric model with four binding sites is essential for anticonvulsant activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / chemistry*
  • Anticonvulsants / pharmacology
  • Binding Sites
  • Models, Molecular*
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Rats
  • Semicarbazones / chemistry*
  • Semicarbazones / pharmacology

Substances

  • Anticonvulsants
  • Oxadiazoles
  • Semicarbazones