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

• DOI: 10.1002/cmdc.201300482
• Publication Date: 2014-01-20T15:09:27Z
• Authors: Joël Mercier; Laurence Archen; Véronique Bollu; Stéphane Carré; Yves Evrard; Eric Jnoff; Benoît Kenda; Bénédicte Lallemand; Philippe Michel; Florian Montel; Florence Moureau; Nathalie Price; Yannick Quesnel; Xavier Sauvage; Anne Valade; Laurent Provins
• Keywords: Levetiracetam; Radioligand

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