Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2A receptor.
J Enzyme Inhib Med Chem
; 32(1): 850-864, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28661196
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.
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Base de dados:
MEDLINE
Assunto principal:
Benzoxazóis
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Desenho de Fármacos
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Receptor A2A de Adenosina
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Antagonistas do Receptor A2 de Adenosina
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article