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Abstract
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.
Acknowledgements
We express our thanks to the 300 MHz NMR facilities funded by the Region Nord-Pas de Calais (France), the Ministere de la Jeunesse, de l’Education Nationale et de la Recherche (MJENR) and the Fonds Europeens de Developpement Regional (FEDER). This work was supported by Lille 2 University, ANR “Adoratau”, Comue Univ Lille Nord de France. Romain Duroux is the recipient of a fellowship from Lille 2 University.
Disclosure statement
No potential conflict of interest was reported by the authors.