Journal of Enzyme Inhibition and Medicinal Chemistry | |
Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2A receptor | |
Nicolas Renault1  Patricia Melnyk2  Saïd Yous2  Romain Duroux2  David Blum2  Laurence Agouridas2  Luisa V. Lopes3  Joana Esteves Cuelho3  | |
[1] INSERM, CHU Lille, U995 – LIRIC – Lille Inflammation Research International Center, Universite de Lille;INSERM, CHU Lille, UMR-S 1172 – JPArc – Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Universite de Lille;Instituto de Medecina Molecular; | |
关键词: Benzoxazole; A2A receptor; solubility; neurodegenerative disease; | |
DOI : 10.1080/14756366.2017.1334648 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown