Development of Bicyclo[3.1.0]hexane-Based A₃ Receptor Ligands: Closing the Gaps in the Structure-Affinity Relationships.

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.

SUBMITTER: Lemmerhirt JP 

PROVIDER: S-EPMC9000336 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature