Pomeisl Karel, Votruba Ivan, Holý Antonín, Pohl Radek
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):1025-8. doi: 10.1080/15257770701508679.
In the present study, we synthesized a series of pyrimidine acyclic nucleoside phosphonates bearing a number of substituents in C-5 position of uracil moiety and in the N-1-side chain. In addition, we have investigated in particular the novel syntheses of fluorinated derivatives substituted in the N-1-side chain and uracil C-5 position because fluorine-containing substituents are often powerful modifiers of chemical and biological properties. The obtained compounds exhibit a considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In contrast, the synthesized phosphonates are not efficient inhibitors of E. coli and human thymidine phosphorylase.
在本研究中，我们合成了一系列嘧啶无环核苷膦酸酯，这些化合物在尿嘧啶部分的C-5位和N-1侧链上带有多个取代基。此外，我们特别研究了在N-1侧链和尿嘧啶C-5位被取代的氟化衍生物的新合成方法，因为含氟取代基通常是化学和生物学性质的强效调节剂。所得到的化合物对SD淋巴瘤的胸苷磷酸化酶表现出相当强的抑制效力。相比之下，合成的膦酸酯对大肠杆菌和人胸苷磷酸化酶不是有效的抑制剂。
