Medicinal Chemistry · 2014 · 14 citations · 0 references
MedicineMedicinal ChemistryPharmacologyClinical PharmacologyDrug DiscoveryMolecular PharmacologyDiabetes ManagementDiabetes MellitusDiabetes PharmacotherapyEnzyme InhibitionOral Antidiabetic AgentsSodium-glucose Cotransporter 2 InhibitorsAntidiabetic ActivityBlood Glucose RegulationGlucose Transporter 2Sodium-dependent Glucose TransportSodium-dependent Glucose TransportersSodium-glucose CotransportSodium-glucose Cotransporter 2 InhibitionType 2 Diabetes Treatment
Systematic mono-deoxylation of the four hydroxyl groups in the glucose moiety in dapagliflozin led to the discovery of 6-deoxydapagliflozin 1 as a more active sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor (IC50 = 0.67 nM against human SGLT2 (hSGLT2) vs 1.16 nM for dapagliflozin). It exhibited more potent blood glucose inhibitory activity in rat oral glucose tolerance test and induced more urinary glucose in rat urinary glucose excretion test than its parent compound dapagliflozin.