2. Academic Validation
  3. 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

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

Affiliation

  • 1 Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. lakjeong@ewha.ac.kr
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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