Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences (FFW), Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
Bioorg Med Chem. 2013 Jan 1;21(1):257-68. doi: 10.1016/j.bmc.2012.10.018. Epub 2012 Nov 5.
We report the synthesis of 5'-modified thymidines (16, 18, 21, 23) and 5,5'-bis-substituted 2'-deoxyuridine analogues (30, 47) as inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). These analogues were evaluated for their capacity to inhibit TMPKmt and solely two 5'-modified thymidines were found to possess moderate inhibitory activity. In addition, a feasibility study of protecting groups for the 5-CH(2)OH moiety of 2'-deoxyuridines is described that enables to introduce the desired 5'-modification.
我们报告了 5'-修饰的胸苷（16、18、21、23）和 5,5'-双取代的 2'-脱氧尿苷类似物（30、47）的合成，它们是结核分枝杆菌胸苷单磷酸激酶（TMPKmt）的抑制剂。这些类似物的抑制 TMPKmt 的能力进行了评估，仅发现两种 5'-修饰的胸苷具有中等抑制活性。此外，还描述了保护 2'-脱氧尿苷 5-CH(2)OH 部分的保护基的可行性研究，该研究能够引入所需的 5'-修饰。
