Lin Li, Shen Qiang, Chen Guo-Rong, Xie Juan
PPSM, ENS Cachan, CNRS, UniverSud, 61 av President Wilson, F-94230 Cachan, France.
Bioorg Med Chem. 2008 Nov 15;16(22):9757-63. doi: 10.1016/j.bmc.2008.09.066. Epub 2008 Sep 30.
Protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for type 2 diabetes. We have successfully synthesized dimeric acetylated and benzoylated beta-C-d-glucosyl and beta-C-D-galactosyl 1,4-dimethoxy benzenes or naphthalenes by click chemistry. These compounds were further transformed into the corresponding beta-C-D-glycosyl-1,4-quinone derivatives by CAN oxidation. The in vitro inhibition test showed that dimeric benzoylated beta-C-D-glycosyl 1,4-dimethoxybenzenes or 1,4-benzoquinones were good inhibitors of PTP1B (IC(50): 0.62-0.88 miroM), with no significant difference between gluco and galacto derivatives.
蛋白酪氨酸磷酸酶1B（PTP1B）已成为2型糖尿病一个很有前景的靶点。我们已通过点击化学成功合成了二聚体乙酰化和苯甲酰化的β-C-D-葡糖基和β-C-D-半乳糖基1,4-二甲氧基苯或萘。这些化合物通过CAN氧化进一步转化为相应的β-C-D-糖基-1,4-醌衍生物。体外抑制试验表明，二聚体苯甲酰化的β-C-D-糖基1,4-二甲氧基苯或1,4-苯醌是PTP1B的良好抑制剂（IC(50)：0.62 - 0.88 μM），葡糖基和半乳糖基衍生物之间无显著差异。
