Journal of Medicinal Chemistry vol. 46, no. 18, pp. 3775 - 3777
4′-Thio analogues 3-5 of Cl-IB-MECA (2) (Ki = 1.0 ± 0.2 nM at the human A3 adenosine receptor) were synthesized from D-gulono-γ-lactone via 4-thioribosyl acetate 14 as the key intermediate. All synthesized 4′-thionucleosides exhibited higher binding affinity to the human A3 adenosine receptor than Cl-IB-MECA, among which 4 showed the most potent binding affinity (Ki = 0.28 ± 0.09 nM). 4 was also selective for A3 vs human A1 and human A2A receptors by 4800- and 36000-fold, respectively.