Extended N(6) substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor.
Bioorg Med Chem Lett
; 24(15): 3302-6, 2014 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-24969016
ABSTRACT
2-Arylethynyl-(N)-methanocarba adenosine 5'-methyluronamides containing rigid N(6)-(trans-2-phenylcyclopropyl) and 2-phenylethynyl groups were synthesized as agonists for probing structural features of the A3 adenosine receptor (AR). Radioligand binding confirmed A3AR selectivity and N(6)-1S,2R stereoselectivity for one diastereomeric pair. The environment of receptor-bound, conformationally constrained N(6) groups was explored by docking to an A3AR homology model, indicating specific hydrophobic interactions with the second extracellular loop able to modulate the affinity profile. 2-Pyridylethynyl derivative 18 was administered orally in mice to reduce chronic neuropathic pain in the chronic constriction injury model.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor A3 de Adenosina
/
Antagonistas do Receptor A3 de Adenosina
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Nucleosídeos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article