Development of Bicyclo[3.1.0]hexane-Based A3 Receptor Ligands: Closing the Gaps in the Structure-Affinity Relationships.
Molecules
; 27(7)2022 Mar 31.
Article
em En
| MEDLINE
| ID: mdl-35408685
ABSTRACT
The adenosine A3 receptor is a promising target for treating and diagnosing inflammation and cancer. In this paper, a series of bicyclo[3.1.0]hexane-based nucleosides was synthesized and evaluated for their P1 receptor affinities in radioligand binding studies. The study focused on modifications at 1-, 2-, and 6-positions of the purine ring and variations of the 5'-position at the bicyclo[3.1.0]hexane moiety, closing existing gaps in the structure-affinity relationships. The most potent derivative 30 displayed moderate A3AR affinity (Ki of 0.38 µM) and high A3R selectivity. A subset of compounds varied at 5'-position was further evaluated in functional P2Y1R assays, displaying no off-target activity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptor A3 de Adenosina
/
Hexanos
Limite:
Animals
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha