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

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Duroux, Romain | Renault, Nicolas | Esteves, Joana | Agouridas, Laurence | Blum, David | Lopes, Luisa | Melnyk, Patricia | Yous, Saïd

Edité par CCSD ; Informa Healthcare -

International audience. 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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