N6-substituted D-4′-thioadenosine-5′-methyluronamides:: Potent and selective agonists at the human A3 adenosine receptor
N6-substituted D-4′-thioadenosine-5′-methyluronamides:: Potent and selective agonists at the human A3 adenosine receptor
复制标题
DOI：
10.1021/jm034098e
复制
发表时间：
2003-08-28
影响因子：
7.3
通讯作者：
Jacobson, KA
中科院分区：
文献类型：
--
作者：
Jeong, LS;Jin, DZ;Jacobson, KA
Cl-IB-MECA（2）的4 ′-硫代类似物3-5（在人A（3）腺苷受体处Ki = 1.0 +/-0.2 nM）由D-古洛糖基-γ-内酯通过4-硫代核糖基乙酸酯14作为关键中间体合成。所有合成的4-硫代糖苷与人A（3）腺苷受体的结合亲和力均高于Cl-IB-MECA，其中4显示出最强的结合亲和力（Ki = 0.28 +/- 0.09 nM）。4对A（3）受体的选择性也比人A（1）和人A（2A）受体的选择性分别高出4800倍和36000倍。
4'-Thio analogues 3-5 of Cl-IB-MECA (2) (K-i = 1.0 +/- 0.2 nM at the human A(3) adenosine receptor) were synthesized from D-gulono-gamma-lactone via 4-thioribosyl acetate 14 as the key intermediate. All synthesized 4-thionucleosides exhibited higher binding affinity to the human A(3) adenosine receptor than Cl-IB-MECA, among which 4 showed the most potent binding affinity (K-i = 0.28 +/- 0.09 nM). 4 was also selective for A(3) vs human A(1) and human A(2A) receptors by 4800- and 36000-fold, respectively.