Synthesis of 3′,5′-Cyclic Phosphate and Thiophosphate Esters of 2′-C-Methyl Ribonucleosides
作者:Anna Leisvuori、Zafar Ahmed、Mikko Ora、Leonid Beigelman、Lawrence Blatt、Harri Lönnberg
DOI:10.1002/hlca.201200099
日期:2012.9
2′‐C‐Methylnucleosides are known to exhibit antiviral activity against Hepatitis C virus. Since the inhibitory activity depends on their intracellular conversion to 5′‐triphosphates, dosing as appropriately protected 5′‐phosphates or 5′‐phosphorothioates appears attractive. For this purpose, four potential pro‐drugs of 2′‐C‐methylguanosine, i.e., 3′,5′‐cyclic phosphorothioate of 2′‐C‐methylguanosine
已知2'- C-甲基核苷具有抗丙型肝炎病毒的抗病毒活性。由于抑制活性取决于它们在细胞内转化为5'-三磷酸的能力,因此以适当保护的5'-磷酸或5'-硫代磷酸酯的剂量给药似乎很有吸引力。为了这个目的,2'-四潜在前药Ç -methylguanosine,即,2'-的5'-环硫代磷酸酯,3' ç -methylguanosine和2'- Ç,Ò 6 -dimethylguanosine,1和2分别中,小号- [(新戊酰氧基)甲基] 2'酯ç,Ò 6-dimethylguanosine 3',5'-环硫代磷酸酯和Ó的甲基酯2'- Ç,ö 6 -dimethylguanosine 3',5'-环磷酸,3和4,分别为已被制备。