Design, synthesis, computational and biological evaluation of new anxiolytics

Bioorg Med Chem. 2004 Dec 15;12(24):6559-68. doi: 10.1016/j.bmc.2004.09.016.


New anxiolytics have been discovered by prediction of biological activity with computer programs pass and derek for a heterogeneous set of 5494 highly chemically diverse heterocyclic compounds (thiazoles, pyrazoles, isatins, a-fused imidazoles and others). The majority of tested compounds exhibit the predicted anxiolytic effect. The most potent activity was found in 2-(4-nitrophenyl)-3-(4-phenylpiperazinomethyl)imidazo[1,2-a]pyridine 8, 1-[(4-bromophenyl)-2-oxoethyl]-3-(1,3-dioxolano)-2-indolinone 3, 5-hydroxy-3-methoxycarbonyl-1-phenylpyrazole 5 and 2-(4-fluorophenyl)-3-(4-methylpiperazinomethyl)imidazo[1,2-a]pyridine 7. The application of the computer-assisted approach significantly reduced the number of synthesized and tested compounds and increased the chance of finding new chemical entities (NCEs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemical synthesis*
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / pharmacology*
  • Computational Biology
  • Computer Simulation*
  • Drug Design
  • Expert Systems
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / pharmacology
  • Learning / drug effects
  • Motor Activity / drug effects
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship


  • Anti-Anxiety Agents
  • Heterocyclic Compounds