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Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A_2A receptor.

ABSTRACT: The development of adenosine A_2A 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 A_2AR 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 A_2A 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 (K_i = 10 μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation.

SUBMITTER: Duroux R

PROVIDER: S-EPMC6445171 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Duroux Romain R Renault Nicolas N Cuelho Joana Esteves JE Agouridas Laurence L Blum David D Lopes Luisa V LV Melnyk Patricia P Yous Saïd S

Journal of enzyme inhibition and medicinal chemistry 20171201 1

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 ...[more]

PMID: 28661196

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