Translations:Discovery and development of gliflozins/17/en

Most of the reported SGLT-2 inhibitors are glucoside analogs that can be tracked to the o-aryl glucoside found in the nature. The problem with using o-glucosides as SGLT-2 inhibitors is instability that can be tracked to degradation by β-glucosidase in the small intestine. Because of that, o-glucosides given orally have to be prodrug esters. These prodrugs go through changes in the body leading to carbon–carbon bond between the glucose and the aglycone moiety so c-glucoside are formed from the o-glucosides. C-glucosides have a different pharmacokinetic profile than o-glucosides (e.g. half-life and duration of action) and are not degraded by the β-glucosidase. The first discovered c-glucoside was the drug dapagliflozin. Dapagliflozin was the first highly selective SGLT-2-inhibitor approved by the European Medicines Agency. All SGLT-2 inhibitors in clinical development are prodrugs that have to be converted to its active ‘A’ form for activity.