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

Journal of Enzyme Inhibition and Medicinal Chemistry

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