Discovery of heterocyclic nonacetamide synaptic vesicle protein 2A (SV2A) ligands with single-digit nanomolar potency: opening avenues towards the first SV2A positron emission tomography (PET) ligands

ChemMedChem. 2014 Apr;9(4):693-8. doi: 10.1002/cmdc.201300482. Epub 2014 Jan 20.


The role of the synaptic vesicle protein 2A (SV2A) protein, target of the antiepileptic drug levetiracetam, is still mostly unknown. Considering its potential to provide in vivo functional insights into the role of SV2A in epileptic patients, the development of an SV2A positron emission tomography (PET) tracer has been undertaken. Using a 3D pharmacophore model based on close analogues of levetiracetam, we report the rationale design of three heterocyclic non-acetamide lead compounds, UCB-A, UCB-H and UCB-J, the first single-digit nanomolar SV2A ligands with suitable properties for development as PET tracers.

Keywords: epilepsy; imaging agents; levetiracetam; positron emission tomography (PET); synaptic vesicle proteins; tracers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides* / chemical synthesis
  • Acetamides* / chemistry
  • Animals
  • Drug Discovery*
  • Heterocyclic Compounds* / chemical synthesis
  • Heterocyclic Compounds* / chemistry
  • Humans
  • Ligands
  • Male
  • Membrane Glycoproteins / analysis*
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Structure
  • Nerve Tissue Proteins / analysis*
  • Nerve Tissue Proteins / metabolism
  • Positron-Emission Tomography*
  • Radioactive Tracers
  • Rats
  • Rats, Wistar


  • Acetamides
  • Heterocyclic Compounds
  • Ligands
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Radioactive Tracers
  • SV2A protein, human