Medicinal Chemistry Laboratory, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan.
Curr Top Med Chem. 2010;10(4):411-8. doi: 10.2174/156802610790980567.
Plasma glucose is continuously filtered through the glomerulus and then is reabsorbed via the transcellular transport system of proximal tubules in the kidney. The glucose reabsorption system in the kidney is mediated by sodium-dependent glucose cotransporters (SGLTs). Most of filtered glucose is reabsorbed by the low affinity, high capacity SGLT2 located in the proximal renal tubule. SGLT2 inhibitors, such as T-1095, enhance urinary glucose excretion and consequently lower blood glucose levels independent of insulin action. The principle behind SGLT inhibition involves the amelioration of diabetic conditions without increasing body weight and the risk of hypoglycemia. A number of SGLT2 inhibitors are being developed for the treatment of diabetes. This review offers the summary of structure-activity relationships (SARs) and pharmacological profiles of T-1095 and diverse SGLT2 inhibitors.
血浆葡萄糖通过肾小球不断过滤，然后通过肾脏近端小管的细胞间转运系统被重吸收。肾脏中的葡萄糖重吸收系统由钠依赖性葡萄糖协同转运蛋白（SGLTs）介导。大部分滤过的葡萄糖被位于近端肾小管中的低亲和力、高容量的 SGLT2 重吸收。SGLT2 抑制剂，如 T-1095，可增强尿葡萄糖排泄，从而降低血糖水平，而不依赖于胰岛素的作用。SGLT 抑制的原理涉及在不增加体重和低血糖风险的情况下改善糖尿病状况。目前正在开发多种 SGLT2 抑制剂用于治疗糖尿病。本综述总结了 T-1095 和不同 SGLT2 抑制剂的结构-活性关系（SAR）和药理学特征。
