Discovery of a new nucleoside template for human A3 adenosine receptor ligands: D-4'-thioadenosine derivatives without 4'-hydroxymethyl group as highly potent and selective antagonists

  • J Med Chem. 2007 Jul 12;50(14):3159-62. doi: 10.1021/jm070259t.
Lak Shin Jeong  1 ,  Seung Ah Choe ,  Prashantha Gunaga ,  Hea Ok Kim ,  Hyuk Woo Lee ,  Sang Kook Lee ,  Dilip K Tosh ,  Amit Patel ,  Krishnan K Palaniappan ,  Zhan-Guo Gao ,  Kenneth A Jacobson ,  Hyung Ryong Moon
Affiliations
  • 1. Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. [email protected]
PMID: 17555308 DOI: 10.1021/jm070259t
Abstract

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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