Discovery of a New Nucleoside Template for Human A 3 Adenosine Receptor Ligands: d -4‘-Thioadenosine Derivatives without 4‘-Hydroxymethyl Group as Highly Potent and Selective Antagonists

Department of Laboratory Medicine, Ewha Womans University, Sŏul, Seoul, South Korea
Journal of Medicinal Chemistry (Impact Factor: 5.45). 08/2007; 50(14):3159-62. DOI: 10.1021/jm070259t
Source: PubMed


Truncated D-4'-thioadenosine derivatives lacking the 4'-hydroxymethylene moiety were synthesized starting from D-mannose, using cyclization to the 4-thiosugar and one-step conversion of the diol to the acetate as key steps. At the human A3 adenosine receptor (AR), N6-substituted purine analogues bound potently and selectively and acted as antagonists in a cyclic AMP functional assay. An N6-(3-chlorobenzyl)purine analogue 9b displayed a Ki value of 1.66 nM at the human A3 AR. Thus, truncated D-4'-thioadenosine is an excellent template for the design of novel A3 AR antagonists to act at both human and murine species.

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