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Bioorg Med Chem. 2009 Dec 1;17(23):8003-11. doi: 10.1016/j.bmc.2009.10.011. Epub 2009 Oct 12.

Design and synthesis of N(6)-substituted-4'-thioadenosine-5'-uronamides as potent and selective human A(3) adenosine receptor agonists.

Author information

1
Department of Bioinspired Science and Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.

Abstract

On the basis of a bioisosteric rationale, 4'-thionucleoside analogues of IB-MECA (N(6)-(3-Iodo-benzyl)-9-(5'-methylaminocarbonyl-beta-d-ribofuranosyl)adenine), which is a potent and selective A(3) adenosine receptor (AR) agonist, were synthesized from d-gulonic acid gamma-lactone. The 4'-thio analogue (5h) of IB-MECA showed extremely high binding affinity (K(i)=0.25 nM) at the human A(3)AR and was more potent than IB-MECA (K(i)=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 A(3)AR binding, although small alkyl analogues were more potent.

PMID:
19879151
PMCID:
PMC2797373
DOI:
10.1016/j.bmc.2009.10.011
[Indexed for MEDLINE]
Free PMC Article

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