KU Leuven, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Bioorg Med Chem Lett. 2013 Jan 1;23(1):132-7. doi: 10.1016/j.bmcl.2012.10.139. Epub 2012 Nov 15.
Starting from a known H(4)R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K(i)=0.5 μM), its lacks selectivity with a K(i) value for the hH(3)R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K(i) values of less than 1 μM at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands.
从基于嘧啶骨架的已知 H(4)R 配体出发，我们已经制备了一系列基于吡咯并[2,3-d]嘧啶骨架的新型类似物。虽然原始嘧啶同系物对 hH(4)R 具有良好的亲和力（K(i)=0.5 μM），但其对 hH(3)R 的选择性较差，K(i) 值为 1 μM。在所合成的新吡咯并[2,3-d]嘧啶中，有几个类似物在 hH(4)R 上的 K(i) 值低于 1 μM，并且显示出改善的选择性特征。因此，这些系列代表了发现新型 hH(4)R 配体的有趣起点。
