Abstract
On the basis of a bioisosteric rationale, 4′-thionucleoside analogues of IB-MECA (N6-(3-Iodo-benzyl)-9-(5′-methylaminocarbonyl-β-d- ribofuranosyl)adenine), which is a potent and selective A3 adenosine receptor (AR) agonist, were synthesized from d-gulonic acid γ-lactone. The 4′-thio analogue (5h) of IB-MECA showed extremely high binding affinity (Ki = 0.25 nM) at the human A3AR and was more potent than IB-MECA (Ki = 1.4 nM). Bulky substituents at the 5′-uronamide position, such as cyclohexyl and 2-methylbenzyl, in this series of 2-H nucleoside derivatives were tolerated in A3AR binding, although small alkyl analogues were more potent.
Original language | English |
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Pages (from-to) | 8003-8011 |
Number of pages | 9 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 17 |
Issue number | 23 |
DOIs | |
State | Published - 1 Dec 2009 |
Keywords
- 4′-Thionucleosides
- A adenosine receptor
- Agonist
- Binding affinity