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Synthèse et évaluation biologique de ligands multi-cibles dirigés contre le système sérotoninergique

Abstract : Alzheimer’s disease is the most common senile dementia in the world. It is an irreversible neurodegenerative disease whose main neuropathological hallmarks are β-amyloid peptide aggregation and hyperphosphorylation of tau protein. Despite numerous clinical trials, Alzheimer’s disease remains incurable. Indeed, this pathology is extremely complex and involves the dysfunction of multi-systems. That is why, one of the recently developed therapeutic approaches lays in the design of multi-target-directed ligands. These molecules are capable to simultaneously engage several targets and therefore represent an innovative approach to treat complex disease such as neurodegenerative disorders. Within the laboratory, a dual-activity drug candidate (acetylcholinesterase inhibitor and 5-HT4 receptor agonist) named donecopride was recently described. Thanks to the promising results obtained with donecopride, a new series of triple-activity compounds has been synthesized. This new series combines an additional activity that aims to block the 5-HT6 receptors. This thesis describes the synthesis and the in vitro and in vivo evaluation of these new triple-acting compounds.
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https://tel.archives-ouvertes.fr/tel-03788480
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Submitted on : Monday, September 26, 2022 - 4:13:31 PM
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Bérénice Hatat. Synthèse et évaluation biologique de ligands multi-cibles dirigés contre le système sérotoninergique. Médecine humaine et pathologie. Université Montpellier, 2019. Français. ⟨NNT : 2019MONTT034⟩. ⟨tel-03788480⟩

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