Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists

Bioorg Med Chem Lett. 2005 Jun 15;15(12):3126-9. doi: 10.1016/j.bmcl.2005.04.018.

Abstract

A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents. Conformational analysis and superimposition of energy minima conformers of the designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. Electroshock and pentylenetetrazole-induced lethal convulsion tests showed that the introduction of an amino group in position 2 of 1,3,4-oxadiazole ring and a fluoro substituent at para position of benzylthio moiety had the best anticonvulsant activity. It seems this effect is mediated through benzodiazepine receptors mechanism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants* / chemical synthesis
  • Anticonvulsants* / pharmacology
  • Benzodiazepines / chemistry
  • Benzodiazepines / metabolism*
  • Convulsants / toxicity
  • Diazepam / pharmacology
  • Drug Design*
  • Electroshock
  • Flumazenil / pharmacology
  • GABA Modulators / pharmacology
  • GABA-A Receptor Agonists*
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Pentylenetetrazole / toxicity
  • Seizures / etiology
  • Seizures / prevention & control
  • Structure-Activity Relationship

Substances

  • Anticonvulsants
  • Convulsants
  • GABA Modulators
  • GABA-A Receptor Agonists
  • Oxadiazoles
  • Benzodiazepines
  • Flumazenil
  • Diazepam
  • Pentylenetetrazole