发现 6-去氧达格列净作为一种高效的钠依赖性葡萄糖共转运蛋白 2（SGLT2）抑制剂，用于治疗 2 型糖尿病。
Discovery of 6-deoxydapagliflozin as a highly potent sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.
机构信息
School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P.R. China and Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, 308 An Shan Xi Dao, Nankai District, Tianjin 300193, P.R. China.
出版信息
Med Chem. 2014 May;10(3):304-17. doi: 10.2174/15734064113096660051.
Systematic mono-deoxylation of the four hydroxyl groups in the glucose moiety in dapagliflozin led to the discovery of 6-deoxydapagliflozin 1 as a more active sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor (IC50 = 0.67 nM against human SGLT2 (hSGLT2) vs 1.16 nM for dapagliflozin). It exhibited more potent blood glucose inhibitory activity in rat oral glucose tolerance test and induced more urinary glucose in rat urinary glucose excretion test than its parent compound dapagliflozin.
对达格列净葡萄糖部分的四个羟基进行系统单去氧，发现 6-去氧达格列净 1 是一种更有效的钠依赖性葡萄糖共转运蛋白 2（SGLT2）抑制剂（对人 SGLT2（hSGLT2）的 IC50 为 0.67 nM，而达格列净为 1.16 nM）。在大鼠口服葡萄糖耐量试验中，它表现出更强的降血糖活性，在大鼠尿葡萄糖排泄试验中诱导的尿葡萄糖量也多于其母体化合物达格列净。
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