6-BENZYLPHENYL-2-SULFURETETRAGHYDROPYRAN-3,4,5-TRIOL DERIVATIVES AS SODIUM-GLUCOSE CO-TRANSPORTER INHIBITORS 1 AND 2 FOR USE IN DIABETIC PATIENTS

摘要

1. A dose of 300 mg / day or less (for example, 250, 200, 150, 100 or 50 mg / day or less) of a dual inhibitor of NGT1 / 2 (sodium glucose cotransporter 1/2) of the formula or its pharmaceutically acceptable salt for use in improving the cardiovascular or metabolic health of patients with diabetes or pre-diabetic patients taking at that time a DPP-4 (dipeptidyl peptidase-4) inhibitor, where: each R is independently hydrogen, alkyl, aryl or heterocycle; each R is independently hydrogen, hydroxyl, amino , alkyl, aryl, cyano, halogen, heteroalkyl, get erocycle, nitro, C≡CR, OR, SR, SOR, SOR, C (O) R, COR, COH, CON (R) (R), CONH (R), CONH, NHC (O) R or NHSOR; each R is independent means alkyl, aryl or heterocycle; each R independently means hydrogen, hydroxyl, amino, alkyl, aryl, cyano, halogen, heteroalkyl, heterocycle, nitro, C≡CR, OR, SR, SOR, SOR, C (O) R, COR, COH, CON (R) (R), CONH (R), CONH, NHC (O) R or NHSOR; each R is independently alkyl, aryl or heterocycle; m is 1-4; n is 1-3, p is 0-2 ; and where each alkyl, aryl, heteroalkyl or heterocycle is optionally substituted with one or more groups: alkoxy, amino, cyano, halo, hydroxyl or nitro. 2. The dose for use according to claim 1, where improvement means lowering the level of glucose in the blood plasma of a patient on an empty stomach by more than about 50, 55 or 60 mg / dl. The dose for use according to claim 1, wherein improvement means lowering the level of hemoglobin A1c in a patient by more than about 1.0, 1.1, or 1.2%. The dose for use according to claim 1, where improvement means lowering the level of fructosamine in the patient's blood plasma by more than about 30, 40 or 50 μmol / L. The dose for use according to claim 1, wherein improvement means lowering blood pressure in a patient. The dose for use according to claim 1, where the improvement means with