Synthesis and Anticonvulsant Activity Evaluation of 4-Phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one and Its Derivatives

Arch Pharm (Weinheim). 2015 Aug;348(8):564-74. doi: 10.1002/ardp.201500115. Epub 2015 Jun 5.

Abstract

A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones (6a-x) with triazole and other heterocyclic substituents (7-14) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI6o > 25.5, PI6q > 26.0). Compounds 6o and 6q showed significant oral activity against MES-induced seizures in mice, with ED50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline.

Keywords: Anticonvulsant; BIC; Maximal electroshock; Synthesis; Triazole; sc-PTZ.

Publication types

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

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / toxicity
  • Behavior, Animal
  • Bicuculline
  • Brain / drug effects
  • Brain / physiopathology
  • Disease Models, Animal
  • Drug Design*
  • Electroshock
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects
  • Pentylenetetrazole
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / pharmacology*
  • Quinazolinones / toxicity
  • Rotarod Performance Test
  • Seizures / chemically induced
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Structure-Activity Relationship
  • Time Factors
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology*
  • Triazoles / toxicity

Substances

  • Anticonvulsants
  • Quinazolinones
  • Triazoles
  • Pentylenetetrazole
  • Bicuculline