Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591039 | Bioorganic & Medicinal Chemistry Letters | 2014 | 5 Pages |
Abstract
2-Arylethynyl-(N)-methanocarba adenosine 5â²-methyluronamides containing rigid N6-(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 N6-1S,2R stereoselectivity for one diastereomeric pair. The environment of receptor-bound, conformationally constrained N6 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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Organic Chemistry
Authors
Dilip K. Tosh, Silvia Paoletta, Zhoumou Chen, Steven M. Moss, Zhan-Guo Gao, Daniela Salvemini, Kenneth A. Jacobson,