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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

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Development of Bicyclo[3.1.0]hexane-Based A<sub>3</sub> Receptor Ligands: Closing the Gaps in the Structure-Affinity Relationships.

Lemmerhirt Jan Phillip JP Isaak Andreas A Liu Rongfang R Kock Max M Daniliuc Constantin G CG Jacobson Kenneth A KA Heitman Laura H LH Junker Anna A

Molecules (Basel, Switzerland) 20220331 7

The adenosine A<sub>3</sub> 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 pote ...[more]

PMID: 35408685

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