Claims for Patent: 7,781,577

Summary for Patent: 7,781,577

Title:	Inhibitors of sodium glucose co-transporter 2 and methods of their use
Abstract:	Compounds and pharmaceutical compositions comprising them are disclosed that may be useful for the treatment of diseases and disorders such as diabetes and obesity.
Inventor(s):	Bryce Alden Harrison, Spencer David Kimball, Ross Mabon, David Brent Rawlins, Nicole C Goodwin
Assignee:	Lexicon Pharmaceuticals Inc
Application Number:	US11/862,690
Patent Claims:	1. A compound of the formula or a pharmaceutically acceptable salt thereof, wherein: R1 is N(R1A)2; each R1A is independently hydrogen or optionally substituted alkyl, aryl or heterocycle; R2 is fluoro or OR2A; R2A is hydrogen, optionally substituted alkyl, C(O)alkyl, C{O)aryl, or aryl; each R6 is independently hydrogen, hydroxyl, halogen, amino, cyano, nitro, C≡CR6A, OR6A, SR6A, SOR6A, SO2R6A, C(O)R6A, CO2R6A, CO2H, CON(R6A)(R6A), CONH(R6A), CONH2, NHC(O)R6A, NHSO2R6A, or optionally substituted alkyl, aryl or heterocycle; each R6A is independently optionally substituted alkyl, aryl or heterocycle; each R7 is independently hydrogen, hydroxyl, halogen, amino, cyano, nitro, C≡CR7A, OR7A, SR7A, SOR7A, SO2R7A, C(O)R7A, CO2R7A, CO2H, CON(R7A)(R7A), CONH(R7A), CONH2, NHC(O)R7A, NHSO2R7A, or optionally substituted alkyl, aryl or heterocycle; each R7A is independently optionally substituted alkyl, aryl or heterocycle; m is 1-3; and n is 1-3. 2. The compound of claim 1, wherein at least one R1A is hydrogen. 3. The compound of claim 1, wherein at least one R1A is optionally substituted alkyl. 4. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein R1A is independently hydrogen or optionally substituted alkyl, aryl or heterocycle. 5. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein R1A is independently hydrogen or optionally substituted alkyl, aryl or heterocycle. 6. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein: A is optionally substituted aryl, cycloalkyl, or heterocycle; B is optionally substituted aryl, cycloalkyl, or heterocycle; Y is O, S, SO, SO2, NR4, (C(R5)2)p, (C(R5)2)q—C(O)—(C(R5)2)q, (C(R5)2)q—C(O)O—(C(R5)2)q, (C(R5)2)q—OC(O)-(c(R5)2)q, (C(R5)2)q—C(O)NR4—(C(R5)2)q, (C(R5)2)q—NR4C(O)—(C(R5)2)q, or (C(R5)2)q—NR4C(O)NR4—(C(R5)2)q; R1 is OR1A, SR1A, SOR1A, SO2R1A, or R1A; each R1A is independently hydrogen or optionally substituted alkyl, aryl or heterocycle; R2 is fluoro or OR2A; R3 is hydrogen or optionally substituted alkyl, aryl or heterocycle, each of R2A, R2B, and R2C is independently hydrogen, optionally substituted alkyl, C(O)alkyl, C(O)aryl, or aryl; each R4 is independently hydrogen or optionally substituted alkyl; each R5 is independently hydrogen, hydroxyl, halogen, amino, cyano, OR5A, SR5A, or optionally substituted alkyl, each R5A is independently optionally substituted alkyl; p is 0-3; and each q is independently 0-2. 7. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein: A is optionally substituted aryl, cycloalkyl, or heterocycle; R2 is fluoro or OR2A; each of R2A, R2B, and R2C is independently hydrogen, optionally substituted alkyl, C(O)alkyl, C(O)aryl or aryl; R8 is hydrogen or C(O)R8A; R8A is hydrogen or optionally substituted alkyl, alkoxy or aryl; R9A and R9B are each independently OR9C or SR9C, or are taken together to provide O, S or NR9C; and each R9C is independently optionally substituted alkyl, aryl or heterocycle. 8. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein: A is optionally substituted aryl, cycloalkyl, or heterocycle; R2 is fluoro or OR2A; each of R2A, R2B, and R2C is independently hydrogen, optionally substituted alkyl, C(O)alkyl, C(O)aryl or aryl; R3 is hydrogen or optionally substituted alkyl, aryl or heterocycle; R8 is hydrogen or C(O)R8A; R8A is hydrogen or optionally substituted alkyl, alkoxy or aryl; R9A and R9B are each independently OR9C or SR9C, or are taken together to provide O, S or NR9C; and each R9C is independently optionally substituted alkyl, aryl or heterocycle. 9. A pharmaceutical formulation comprising a compound of claim 4 and a pharmaceutically acceptable diluent or excipient. 10. A method of inhibiting sodium glucose co-transporter 2 activity, which comprises contacting sodium glucose co-transporter 2 with an effective amount of a compound of claim 4. 11. A method of decreasing blood glucose in a patient, which comprises administering to the patient an effective amount of a compound of claim 4. 12. A method of increasing the excretion of glucose in the urine of a patient, which comprises administering to the patient an effective amount of a compound of claim 4. 13. A method of restoring insulin sensitivity in a patient, which comprises administering to a patient in need thereof an effective amount of a compound of claim 4. 14. A method of treating or managing a disease or disorder in a patient, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of claim 4, wherein the disease or disorder is atherosclerosis, cardiovascular disease, diabetes (Type 1 or 2), hyperglycemia, hypertension, lipid disorders, obesity, or Syndrome X. 15. The method of claim 14, wherein the disease or disorder is type 2 diabetes. 16. A pharmaceutical formulation comprising a compound of claim 5 and a pharmaceutically acceptable diluent or excipient. 17. A method of inhibiting sodium glucose co-transporter 2 activity, which comprises contacting sodium glucose co-transporter 2 with an effective amount of a compound of claim 5. 18. A method of decreasing blood glucose in a patient, which comprises administering to the patient an effective amount of a compound of claim 5. 19. A method of increasing the excretion of glucose in the urine of a patient, which comprises administering to the patient an effective amount of a compound of claim 5. 20. A method of restoring insulin sensitivity in a patient, which comprises administering to a patient in need thereof an effective amount of a compound of claim 5. 21. A method of treating or managing a disease or disorder in a patient, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of claim 5, wherein the disease or disorder is atherosclerosis, cardiovascular disease, diabetes (Type 1 or 2), hyperglycemia, hypertension, lipid disorders, obesity, or Syndrome X. 22. The method of claim 21, wherein the disease or disorder is type 2 diabetes. 23. The compound of claim 4, wherein R1A is lower alkyl. 24. The compound of claim 5, wherein R1A is lower alkyl. 25. (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6-methylsulfanyl-tetrahydro-pyran-3,4,5-triol or a pharmaceutically acceptable salt thereof. 26. A pharmaceutical formulation comprising (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6-methylsulfanyl-tetrahydro-pyran-3,4,5-triol or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or excipient. 27. A method of treating type 2 diabetes in a patient, which comprises administering to a patient in need thereof a therapeutically effective amount of (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6-methylsulfanyl-tetrahydro-pyran-3,4,5-triol or a pharmaceutically acceptable salt thereof.