Synthesis, anticonvulsant, sedative and anxiolytic activities of novel annulated pyrrolo[1,4]benzodiazepines

Int J Mol Sci. 2014 Sep 18;15(9):16500-10. doi: 10.3390/ijms150916500.

Abstract

Four new pentacyclic benzodiazepine derivatives (PBDTs 13-16) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.

Publication types

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

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemical synthesis*
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use
  • Benzodiazepinones / chemical synthesis*
  • Benzodiazepinones / pharmacology
  • Benzodiazepinones / therapeutic use
  • Exploratory Behavior / drug effects
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Hypnotics and Sedatives / chemical synthesis*
  • Hypnotics and Sedatives / pharmacology
  • Hypnotics and Sedatives / therapeutic use
  • Male
  • Mice
  • Mice, Inbred ICR
  • Molecular Structure
  • Pentobarbital / toxicity
  • Picrotoxin / toxicity
  • Reflex, Abnormal / drug effects
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Strychnine / toxicity

Substances

  • 18-thia-6,14,16,19,20-pentaazapentacyclo(12.6.0.0(2,6).0(8,13).0(15,19))icosa-1(20),8,10,12,15-pentaene-7,17-dione
  • Anti-Anxiety Agents
  • Anticonvulsants
  • Benzodiazepinones
  • Heterocyclic Compounds, 4 or More Rings
  • Hypnotics and Sedatives
  • Picrotoxin
  • Strychnine
  • Pentobarbital