C-aryl glucoside SGLT2 inhibitors and method
AssigneeBristol-Myers Squibb Company
InventorsWilliam N. Washburn, Bruce Ellsworth, Wei Meng, Gang Wu, Philip M. Sher
Life of this patent
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Abstract
A method is provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of a compound of the formula 1 alone or in combination with one or more other antidiabetic agent(s) or other therapeutic agent(s).
Claims24
A method for treating or delaying the progression or onset of diabetes, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, delayed wound healing, insulin resistance, hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, hyperlipidemia, obesity, hypertriglyceridemia, Syndrome X, diabetic complications, atherosclerosis or hypertension, or for increasing high density lipoprotein levels, which comprises administering to a mammalian species in need of treatment a therapeutically effective amount of a compound of formula I having the structure
- 115
- wherein
- R1, R2 and R2a are independently hydrogen, OH, OR5, alkyl, CF3, OCHF2, OCF3, SR5i or halogen, or two of R1, R2 and R2a together with the carbons to which they are attached can form an annelated five, six or seven membered carbocycle or heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2;
- R and R are independently hydrogen, OH, OR5a, OAryl, OCH2Aryl, alkyl, cycloalkyl, CF3, —OCHF2, —OCF3, halogen, —CN, —CO2R5b, —CO2H, COR6b, —CH(OH)R6c, CH(OR5h)R6d, CONR6R6a, —NHCOR5c, —NHSO2R5d, —NHSO2Aryl, Aryl, —SR5e, —SOR5f, —SO2R5g, —SO2Aryl, or a five, six or seven membered heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2, or R3 and R4 together with the carbons to which they are attached form an annelated five, six or seven membered carbocycle or heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2;
- R5, R5a, R5b, R5c, R5d, R5e, R5f, R5g, R5h and R5i are independently alkyl;
- R6, R6a, R6b, R6c, and R are independently hydrogen, alkyl, aryl, alkylaryl or cycloalkyl, or R6 and R6a together with the nitrogen to which they are attached form an annelated five, six or seven membered heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2;
- and
- A is O, S, NH, or (CH2)n where n is 0-3, or a pharmaceutically acceptable salt, stereoisomer, or prodrug ester thereof.
A method for treating type II diabetes which comprises administering to a mammalian species in need of treatment a therapeutically effective amount of a compound of formula I having the structure
- 123
- wherein
- R1, R2 and R2a are independently hydrogen, OH, OR5, alkyl, CF3, OCHF2, OCF3, SR5i or halogen, or two of R1, R2 and R2a together with the carbons to which they are attached can form an annelated five, six or seven membered carbocycle or heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2;
- R3 and R4 are independently hydrogen, OH, OR5a, OAryl, OCH2Aryl, alkyl, cycloalkyl, CF3, —OCHF2, —OCF3, halogen, —CN, CO2R5b, —CO2H, COR6b, CH(OH)R6c, —CH(OR5h)R6d, —CONR6R6a, —NHCOR5c, —NHSO2R5d, —NHSO2Aryl, Aryl, —SR5, —SOR5f, —SO2R5g, —SO2Aryl, or a five, six or seven membered heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2, or R3 and R4 together with the carbons to which they are attached form an annelated five, six or seven membered carbocycle or heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2;
- R5, R5a, R5b, R5c, R5d, R5e, R5f, R5g, R5h and R5i are independently alkyl;
- R6, R6a, R6b, R6c, and R6d are independently hydrogen, alkyl, aryl, alkylaryl or cycloalkyl, or R6 and R6a together with the nitrogen to which they are attached form an annelated five, six or seven membered heterocycle which may contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO2;
- and
- A is O, S, NH, or (CH2)n where n is 0-3, or a pharmaceutically acceptable salt, stereoisomer, or prodrug ester thereof alone or in combination with another antidiabetic agent, an agent for treating the complications of diabetes, an anti-obesity agent, an antihypertensive agent, an antiplatelet agent, an anti-atherosclerotic agent and/or a hypolipidemic agent.
Dependencies are inferred from the claim text.