Synthesis and biological evaluation of thiophene-C-glucosides as sodium-dependent glucose cotransporter 2 inhibitors

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide (Glucotrol),...

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are typically...

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and 'exit' via the...