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 |
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| Authors: | Joël Mercier Laurence Archen Véronique Bollu Stéphane Carré Yves Evrard Dr Eric Jnoff Dr Benoît Kenda Bénédicte Lallemand Dr Philippe Michel Dr Florian Montel Dr Florence Moureau Nathalie Price Dr Yannick Quesnel Dr Xavier Sauvage Dr Anne Valade Dr Laurent Provins |
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| Affiliation: | 1. Global Chemistry, UCB NewMedicines, UCB Pharma, Chemin du Foriest, B‐1420 Braine‐L'Alleud (Belgium);2. Cyclotron Research Center, University of Liège, Allée du 6 Ao?t, Bldg. B30, Sart Tilman, 4000 Liège (Belgium);3. StemCell Sciences UK, Babraham Research Campus, Cambridge, CB22 3AT (UK) |
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| Abstract: | 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. |
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| Keywords: | epilepsy imaging agents levetiracetam positron emission tomography (PET) synaptic vesicle proteins tracers |
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