Synthesis and Anticonvulsant Activity of N-(Substituted)-1-methyl-2,4-dioxo-1,2-dihydroquinazoline-3(4H)-carboxamides

Arch Pharm (Weinheim). 2016 Jul;349(7):566-71. doi: 10.1002/ardp.201600024. Epub 2016 May 27.

Abstract

A series of new N-(substituted)-1-methyl-2,4-dioxo-1,2-dihydroquinazoline-3(4H)-carboxamides were designed, synthesized, and evaluated for their anticonvulsant activity. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock (MES) and pentylenetetrazol (PTZ) test. The most promising compound 4c showed significant anticonvulsant activity with a protective index value of 3.58. The compounds 4a-c were also found to have encouraging anticonvulsant activity in the MES and PTZ screen when compared with the standard drugs, valproate and methaqualone. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drugs.

Keywords: Anticonvulsant; Glycosmicine; MES; Neurotoxicity; PTZ.

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Electroshock
  • Methaqualone / therapeutic use
  • Mice
  • Pentylenetetrazole
  • Picrotoxin / therapeutic use
  • Quinazolines / chemical synthesis*
  • Quinazolines / therapeutic use*
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Structure-Activity Relationship
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • Quinazolines
  • Picrotoxin
  • Valproic Acid
  • Methaqualone
  • Pentylenetetrazole