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Article Dans Une Revue Journal of Enzyme Inhibition and Medicinal Chemistry Année : 2017

Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2A receptor

Résumé

The development of adenosine A2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A2A receptor. Compound F1, with an affinity of 1 μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184 μm) without being cytotoxic at 100 μm. This compound, along with low-molecular weight compound D1 (Ki = 10 μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.
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Dates et versions

hal-02060508 , version 1 (20-12-2023)

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Romain Duroux, Nicolas Renault, Joana Esteves, Laurence Agouridas, David Blum, et al.. Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2A receptor. Journal of Enzyme Inhibition and Medicinal Chemistry, 2017, 32 (1), pp.850-864. ⟨10.1080/14756366.2017.1334648⟩. ⟨hal-02060508⟩
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