Claims for Patent: 8,476,413

Summary for Patent: 8,476,413

Title:	Sulfanyl-tetrahydropyran-based compounds and methods of their use
Abstract:	Sulfanyl-tetrahydropyran-based compounds, pharmaceutical compositions comprising them, and methods of their use for the treatment of diseases and disorders such as diabetes and obesity are disclosed.
Inventor(s):	Bryce Alden Harrison, Spencer David Kimball, Ross Mabon, David Brent Rawlins
Assignee:	Lexicon Pharmaceuticals Inc
Application Number:	US12/858,666
Patent Claims:	1. 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; R1A is independently hydrogen or optionally substituted alkyl, aryl 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; 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. 2. The compound of claim 1, which is of the formula: 3. The compound of claim 2, which is of the formula: wherein: 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. 4. The compound of claim 3, which is of the formula: 5. The compound of claim 4, wherein Y is (C(R4)2)p. 6. The compound of claim 5, wherein p is 1. 7. The compound of claim 4, wherein Y is (C(R5)2)q—C(O)—(C(R5)2)q. 8. The compound of claim 7, wherein each q is independently 0 or 1. 9. The compound of claim 4, wherein R1A is hydrogen. 10. The compound of claim 4, wherein R1A is optionally substituted alkyl. 11. The compound of claim 4, wherein R6 is hydrogen, hydroxyl, halogen, OR6A, or optionally substituted lower alkyl. 12. The compound of claim 11, wherein R6 is hydrogen. 13. The compound of claim 11, wherein R6 is halogen. 14. The compound of claim 11, wherein R6 is hydroxyl. 15. The compound of claim 11, wherein R6 is OR6A. 16. The compound of claim 11, wherein R6 is optionally substituted methyl. 17. The compound of claim 4, wherein R7 is hydrogen, C≡CR7A, OR7A, or optionally substituted lower alkyl. 18. The compound of claim 17, wherein R7 is hydrogen. 19. The compound of claim 17, wherein R7 is C≡CR7A. 20. The compound of claim 19, wherein R7A is optionally substituted monocyclic aryl or heterocycle. 21. The compound of claim 17, wherein R7 is OR7A. 22. The compound of claim 17, wherein R7 is acetylenyl or optionally substituted methyl or ethyl. 23. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein: R1A is independently hydrogen or optionally substituted alkyl, aryl 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; 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. 24. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein: R1A is independently hydrogen or optionally substituted alkyl, aryl or heterocycle; 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. 25. A pharmaceutical formulation comprising a compound of claim 1 and a pharmaceutically acceptable diluent or excipient. 26. 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 1. 27. A method of decreasing blood glucose in a patient, which comprises administering to the patient an effective amount of a compound of claim 1. 28. 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 1. 29. 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 1. 30. A method of treating 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 1, wherein the disease or disorder is atherosclerosis, cardiovascular disease, diabetes (type 1 or 2), hyperglycemia, hypertension, lipid disorders, obesity, or Syndrome X. 31. The method of claim 30, wherein the disease or disorder is type 2 diabetes.