Translations:Discovery and development of gliflozins/24/en

The discovery of T-1095 led to an investigation of how to enhance potency, selectivity and oral bioavailability by adding various substituents to the glycoside core. As an example we can take the change of o-glycosides to c-glycosides by creating a carbon–carbon bond between the glucose and the aglycone moiety. C-glucosides are more stable than o-glucosides which leads to modified half-life and duration of action. These modifications have also led to more specificity to SGLT-2. C-glucosides that have heterocyclic ring at the distal ring or proximal ring are better when it comes to anti-diabetic effect and physicochemical features all together. C-glucoside bearing thiazole at the distal ring on canagliflozin has shown good physicochemical properties that can lead to a clinical development, but still has the same anti-diabetic activity as dapagliflozin, as shown in tables 1 and 2.