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

Article Details

Citation

Copy to clipboard

Choi WJ, Lee HW, Kim HO, Chinn M, Gao ZG, Patel A, Jacobson KA, Moon HR, Jung YH, Jeong LS

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

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

PubMed ID

19879151 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Piclidenoson	Adenosine receptor A3	Ki (nM)	1	N/A	N/A	Details
Piclidenoson	Adenosine receptor A3	Ki (nM)	1.4	N/A	N/A	Details