New A2A adenosine receptor antagonists: a structure-based upside-down interaction in the receptor cavity.
Bioorg Chem
; 92: 103183, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31446240
ABSTRACT
Adenosine receptor antagonists are generally based on heterocyclic core structures presenting substituents of various volumes and chemical-physical profiles. Adenine and purine-based adenosine receptor antagonists have been reported in literature. In this work we combined various substituents in the 2, 6, and 8-positions of 9-ethylpurine to depict a structure-affinity relationship analysis at the human adenosine receptors. Compounds were rationally designed trough molecular modeling analysis and then synthesized and evaluated at radioligand binding studies at human adenosine receptors. The new compounds showed affinity for the human adenosine receptors, with some derivatives endowed with low nanomolar Ki data, in particular at the A2AAR subtype. The purine core proves to be a versatile core structure for the development of novel adenosine receptor antagonists with nanomolar affinity for these membrane proteins.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Purinas
/
Receptor A2A de Adenosina
/
Antagonistas do Receptor A2 de Adenosina
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália