Synthesis of newer indolyl/phenothiazinyl substituted 2-oxo/thiobarbituric acid derivatives as potent anticonvulsant agents

Arzneimittelforschung. 2003;53(5):301-6. doi: 10.1055/s-0031-1297113.

Abstract

2-Amino-5-(heteroarylmethylene)-1,3,4-oxadiazoles/thiadiazoles 7-10 were synthesized by cyclisation of 1-(heteroarylacetyl)semicarbazides/thiosemicarbazides 3-6. 5-(2'-Heteroarylmethylene-5'-aminomethylene-1',3,'4'- oxadiazol-2'-yl/thiadiazol-2'-yl)-2-oxo/thiobarbituric acids 11-18 were synthesized by condensation of compounds 7-10 at the 5th position of 2-oxo/thiobarbituric acids. The newly synthesized compounds showed anticonvulsant activity ranging from 50-90% (seizures protection). Compound 18 (5-(2'-phenothiazinylmethylene-5'-aminomethylene-1',3',4'-thiadiazol-2'- yl)-2-thiobarbituric acid) showed maximum activity being more potent than the reference drug phenytoin sodium (CAS 630-93-3).

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / toxicity
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, Thin Layer
  • Dose-Response Relationship, Drug
  • Electroshock
  • Female
  • Indicators and Reagents
  • Lethal Dose 50
  • Male
  • Mice
  • Phenothiazines / chemical synthesis*
  • Phenothiazines / pharmacology*
  • Phenothiazines / toxicity
  • Phenytoin / pharmacology
  • Rats
  • Seizures / prevention & control
  • Thiobarbiturates / chemical synthesis*
  • Thiobarbiturates / pharmacology*
  • Thiobarbiturates / toxicity

Substances

  • Anticonvulsants
  • Indicators and Reagents
  • Phenothiazines
  • Thiobarbiturates
  • Phenytoin