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

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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.


Arrows indicate 1H,1H-NOESY (blue) and 1H,13C-HMBC (green) correlations for compound 3i.
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Figure 4: Arrows indicate 1H,1H-NOESY (blue) and 1H,13C-HMBC (green) correlations for compound 3i.

Mentions: Similar analysis of the NOESY and HMBC spectra of derivative 3i indicates that this compound behaves as several conformers in solution (Fig. 4). Indeed, the NOESY experiment shows correlations between the two protons in the ortho position (Ho and Ho’) of the phenyl ring and the H5 of the triazole. In this case, the position of the exocyclic amino group in meta position does not allow the formation of a strong H-bond and the C–C bond linking the triazole and the aromatic rings is free to rotate. To our surprise, a cross-peak between the H5 of the triazole and the H3’ was observed (as well as with the anomeric proton), indicating that both syn- and anti-conformers may be present.


Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation
Arrows indicate 1H,1H-NOESY (blue) and 1H,13C-HMBC (green) correlations for compound 3i.
© Copyright Policy - Beilstein
Related In: Results  -  Collection

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

Figure 4: Arrows indicate 1H,1H-NOESY (blue) and 1H,13C-HMBC (green) correlations for compound 3i.
Mentions: Similar analysis of the NOESY and HMBC spectra of derivative 3i indicates that this compound behaves as several conformers in solution (Fig. 4). Indeed, the NOESY experiment shows correlations between the two protons in the ortho position (Ho and Ho’) of the phenyl ring and the H5 of the triazole. In this case, the position of the exocyclic amino group in meta position does not allow the formation of a strong H-bond and the C–C bond linking the triazole and the aromatic rings is free to rotate. To our surprise, a cross-peak between the H5 of the triazole and the H3’ was observed (as well as with the anomeric proton), indicating that both syn- and anti-conformers may be present.

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.