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Synthesis of (Glycopyranosyl‐triazolyl)‐purines and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B (PTP1B)
Author(s) -
Luo Lei,
He XiaoPeng,
Shen Qiang,
Li JingYa,
Shi XiaoXin,
Xie Juan,
Li Jia,
Chen GuoRong
Publication year - 2011
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201000242
Subject(s) - chemistry , moiety , purine , glycosyl , stereochemistry , purine metabolism , glycoconjugate , triazole , combinatorial chemistry , biochemistry , organic chemistry , enzyme
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 Cu I ‐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 IC 50 values in low micromolar range (1.5–11.1 μ 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 ( IC 50 >80 μ M ), whereas MeO‐substituted benzylated bis[galactosyl‐triazolyl]‐purine 16 possessed the best inhibitory activity with an IC 50 value of 1.5 μ M . Additionally, these compounds exhibited 2‐ to 57‐fold selectivity over other PTPs (TCPTP, SHP1, SHP2, and LAR).