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Synthesis of (Glycopyranosyl-triazolyl)-purines and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B (PTP1B)

L. Luo, X. P. He, Q. Shen, J. Y. Li, X. X. Shi, J. Xie, J. Li and G. R. Chen Chem. Biodivers., 2011, 8, 11, 2035-2044

Development of novel purine derivatives has attracted considerable interest, since both purine and purine-based nucleosides display a wide range of crucial biological activities in nature. We report here a novel expansion of these studies by introducing gluco- or galactopyranosyl scaffold to the N- or 9-position (or both) of 6-Cl purine moiety via CuI-catalyzed Huisgen 1,3-dipolar cycloaddition. By such an efficient reaction, a series of glycosyl-triazolyl-purines were successfully synthesized in good yields. Biological evaluation showed that the majority of these glycoconjugates were good PTP1B inhibitors with IC50 values in low micromolar range (1.511.1 mu M). The benzylated sugar derivatives displayed better inhibitory potency than that of the acetylated ones. Replacement of Cl by MeO at C(6) of the purine moiety decreased the inhibition in the case of benzylated (glycosyl-mono-triazolyl)-purines 11 and 12 (IC50>80 mu M), whereas MeO-substituted benzylated bis[galactosyl-triazolyl]-purine 16 possessed the best inhibitory activity with an IC50 value of 1.5 mu M. Additionally, these compounds exhibited 2- to 57-fold selectivity over other PTPs (TCPTP, SHP1, SHP2, and LAR).

Type :

Publication

Dates :

Paru le 14 novembre 2011

Informations complémentaires :

doi 10.1002/cbdv.201000242