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

View Article: PubMed Central - HTML - PubMed

ABSTRACT

A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5’-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM.

No MeSH data available.


General synthetic pathway for the 1,2,3-triazolo-β-hydroxyphosphonate derivatives.
© Copyright Policy - Beilstein
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4979751&req=5

C2: General synthetic pathway for the 1,2,3-triazolo-β-hydroxyphosphonate derivatives.

Mentions: Starting from intermediate 2, the CuAAC reaction was either catalysed by CuI or CuSO4 (Table 1) and gave rise to the fully-protected nucleotides 3a–o (Scheme 2) in moderate to good yields. Removal of the sugar protecting groups (acetyl and benzoyl) in basic conditions resulted in the formation of the nucleotides 4a–q (Scheme 2), which were then treated by trimethylsilyl bromide (TMSBr) to generate the corresponding phosphonic acids. Thus, nucleoside phosphonate analogues 1a–q (Scheme 2) were isolated as their sodium salts with yields ranging from 21 to 77% over three steps. Structures of all final compounds were unambiguously confirmed on the basis of NMR (1H, 13C and 31P) and MS (MS and HRMS) data analysis (see Supporting Information File 1).


Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation
General synthetic pathway for the 1,2,3-triazolo-β-hydroxyphosphonate derivatives.
© Copyright Policy - Beilstein
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4979751&req=5

C2: General synthetic pathway for the 1,2,3-triazolo-β-hydroxyphosphonate derivatives.
Mentions: Starting from intermediate 2, the CuAAC reaction was either catalysed by CuI or CuSO4 (Table 1) and gave rise to the fully-protected nucleotides 3a–o (Scheme 2) in moderate to good yields. Removal of the sugar protecting groups (acetyl and benzoyl) in basic conditions resulted in the formation of the nucleotides 4a–q (Scheme 2), which were then treated by trimethylsilyl bromide (TMSBr) to generate the corresponding phosphonic acids. Thus, nucleoside phosphonate analogues 1a–q (Scheme 2) were isolated as their sodium salts with yields ranging from 21 to 77% over three steps. Structures of all final compounds were unambiguously confirmed on the basis of NMR (1H, 13C and 31P) and MS (MS and HRMS) data analysis (see Supporting Information File 1).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5’-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM.

No MeSH data available.