Chapter Twenty-Three - Case History: ForxigaTM (Dapagliflozin), a Potent Selective SGLT2 Inhibitor for Treatment of Diabetes

• Autores: William N. Washburn
• Localización: Annual reports in medicinal chemistry, ISSN 0065-7743, Vol 49, 2014, págs. 363-382
• Idioma: inglés
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• Resumen

  • Abstract Sodium–glucose cotransporter 2 inhibitors are a novel class of agents for the treatment of type 2 diabetes mellitus. These agents reduce hyperglycemia via a paradigm-breaking insulin-independent mechanism entailing promotion of glucosuria by inhibiting renal recovery of glucose. This JOURter relates the salient events that enabled the evolution from hydrolytically unstable phenolic O-glucosides beginning with natural product phlorizin to glucosidase impervious C-aryl glucosides that culminated with the identification of dapagliflozin. The synthesis and pharmacology of dapagliflozin is briefly summarized. Disclosure of the synthesis and properties of these novel agents prompted the pharmaceutical industry to initiate more than 20 programs seeking C-glucosides that would emulate dapagliflozin.