Synthesis and Evaluation of 5-(o-Tolyl)-1H-tetrazole Derivatives as Potent Anticonvulsant Agents

Arch Pharm (Weinheim). 2017 May;350(5). doi: 10.1002/ardp.201600389. Epub 2017 Apr 18.

Abstract

A series of 5-(o-tolyl)-1H-tetrazole derivatives were synthesized and evaluated for their anticonvulsant activities. 1-(2-Methylbenzyl)-5-(o-tolyl)-1H-tetrazole (3h) showed important anticonvulsant activity against the MES-induced seizures, as well as lower neurotoxicity with an ED50 value of 12.7 mg/kg and a TD50 value of over 500 mg/kg after intraperitoneal injection into mice, providing 3h with a high protective index (TD50 /ED50 ) of over 39.4. The achieved results prove that the distinctive compounds could be valuable as a model for future development, adaptation, and investigation to construct more active analogues.

Keywords: 5-(o-Tolyl)-1H-tetrazole derivatives; Anticonvulsant; Synthesis.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacology*
  • Dose-Response Relationship, Drug
  • Electroshock
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / drug therapy*
  • Pentylenetetrazole
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Structure-Activity Relationship
  • Tetrazoles / administration & dosage
  • Tetrazoles / chemistry
  • Tetrazoles / pharmacology*

Substances

  • Anticonvulsants
  • Neuroprotective Agents
  • Tetrazoles
  • 1H-tetrazole
  • Pentylenetetrazole