Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• : cancer; cN-II inhibitors; nucleotide; phosphonate; triazole; Introduction Nucleotidases are an important family of enzymes involved in the metabolism of nucleotides [1]. In particular, human cytosolic 5’-nucleotidase II (cN-II) catalyses the dephosphorylation of purine 5’-monophosphate derivatives to

• effectiveness of cN-II inhibitors in the treatment of these diseases [4][5]. As a result of our interest in this area, we and others [6] have investigated a number of structure–activity relationships (SAR) [7][8] and various medicinal chemistry approaches [9][10] to identify potential cN-II inhibitors. As part

• library of seventeen 1’-triazolyl beta-hydroxyphosphonate ribonucleoside analogues was synthesized using convenient Cu(I)-catalysed cycloaddition. These derivatives were evaluated as potential cN-II inhibitors on the purified enzyme. Two derivatives including either an aminophenyl or an amido-substituent