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Discovery of a New Nucleoside Template for Human A3 Adenosine Receptor Ligands: <scp>d</scp>-4‘-Thioadenosine Derivatives without 4‘-Hydroxymethyl Group as Highly Potent and Selective Antagonists
- Source :
- Journal of Medicinal Chemistry. 50:3159-3162
- Publication Year :
- 2007
- Publisher :
- American Chemical Society (ACS), 2007.
-
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.
- Subjects :
- Adenosine
Thionucleosides
Chemistry
Ligand
Stereochemistry
Receptor, Adenosine A3
Diol
Adenosine A3 Receptor Antagonists
Purine analogue
CHO Cells
Ligands
Chemical synthesis
In vitro
chemistry.chemical_compound
Cricetulus
Cricetinae
Drug Discovery
Animals
Humans
Molecular Medicine
Moiety
Hydroxymethyl
Nucleoside
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....2954c1667a0fb283556d5c18b0854261