Synthesis and pharmacological evaluation of pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as potential GABAA-R ligands

Bioorg Med Chem. 2017 Mar 15;25(6):1901-1906. doi: 10.1016/j.bmc.2017.02.013. Epub 2017 Feb 11.

Abstract

The synthesis of a new series of 6-phenyl- and 6-benzylpyrazolo[1,5-a]pyrimidin-7(4H)-ones 2a-g and 3a-g, strictly related to derivatives with pyrazolobenzotriazine (PBT) and pyrazoloquinazoline (PQ) scaffold, was realized. The in vitro GABAA-receptor subtype affinity was evaluated and from preliminary pharmacological studies, compound 3g shows anxiolytic-like effect at 10-30mg/kg.

Keywords: Drug design; GABA(A); Pyrazolo[1,5-a]pyrimidin-7(4H)one; Receptor.

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
  • Cattle
  • Dose-Response Relationship, Drug
  • Ligands
  • Male
  • Mice
  • Pyrazoles / chemistry*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism*
  • Structure-Activity Relationship

Substances

  • Anti-Anxiety Agents
  • Ligands
  • Pyrazoles
  • Pyrimidines
  • Receptors, GABA-A