Details for Patent: 7,816,331

Title:	Substituted indazole-O-glucosides
Abstract:	Substituted indazole-O-glucosides, compositions containing them, and methods of using them, for example for the treatment of diabetes and Syndrome X are disclosed.
Inventor(s):	Patel; Mona (Belle Mead, NJ), Rybczynski; Philip J. (Branchburg, NJ), Urbanski; Maud (Flemington, NJ), Zhang; Xiaoyan (Belle Mead, NJ)
Assignee:	Janssen Pharmaceutica NV (BE)
Filing Date:	Sep 22, 2009
Application Number:	12/564,421
Claims:	1. A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a subject, comprising (a) administering to said subject a jointly effective amount of a compound of formula (II) ##STR00032## wherein R.sup.1 is H or C.sub.1-4 alkyl; R.sup.2 is H, F, Cl, methoxy, or C.sub.1-3 alkyl; Q is --(CH.sub.2).sub.n-- where n=0, 1, or 2; or, where R.sup.2 is H, F, Cl, or methoxy, then Q can also be selected from --CH.sub.2--S--; Z is substituted or unsubstituted, and is selected from C.sub.3-7 cycloalkyl, phenyl, benzhydryl, 5- or 6-membered heteroaryl having 1 or 2 heteroatoms independently selected from N, O, and S, a biaryl, and a 9- or 10-membered fused bicyclyl or fused heterobicyclyl, wherein each fused heterobicyclyl has between 1 and 4 heteroatoms independently selected from N, O, and S; P=H or acetyl; or a pharmaceutically acceptable salt thereof, (b) administering to said subject a jointly effective amount of a second antidiabetic agent, and (c) administering to said subject a jointly effective amount of a third antidiabetic agent. 2. The method of claim 1, wherein the third antidiabetic agent is selected from (aa) insulins, (bb) insulin analogues; (cc) insulin secretion modulators, and (dd) insulin secretagogues. 3. The method of claim 1, wherein the second antidiabetic agent is an RXR agonist. 4. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complications thereof is selected from IDDM, NIDDM, IGT, IFG, obesity, nephropathy, neuropathy, retinopathy, atherosclerosis, polycystic ovarian syndrome, hypertension, ischemia, stroke, heart disease, irritable bowel disorder, inflammation, and cataracts. 5. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complication thereof is IDDM. 6. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complications thereof is NIDDM. 7. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complications thereof is IGT or IFG. 8. The method of claim 1, wherein R.sup.1 is H. 9. The method of claim 1, wherein R.sup.2 is H, methyl, or ethyl. 10. The method of claim 1, wherein Q is --(CH.sub.2).sub.n-- and n is 1 or 2. 11. The method of claim 1, wherein Z is independently substituted with between 1 and 3 substituents independently selected from C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, halo, hydroxy, cyano, amino, C.sub.1-4 alkylthio, C.sub.1-4 aminoalkyl, mono- and di(C.sub.1-4 alkyl)amino, phenyl, 5-6 membered heterocyclyl containing between 1 and 3 heteroatoms independently selected from N, S, and O; and wherein the substituent(s) on Z can be further independently substituted with between 1 and 3 substituents independently selected from C.sub.1-4 alkoxy, C.sub.1-4 alkyl, halo, hydroxy, cyano, amino, C.sub.1-4 alkylthio, phenoxy, --CONR.sup.aR.sup.b, --NHSO.sub.2R.sup.a, and --SO.sub.2NR.sup.aR.sup.b where each of R.sup.a and R.sup.b is independently selected from H and C.sub.1-4 alkyl. 12. The method of claim 1, wherein Z is phenyl, cyclopentyl, cyclohexyl, 4-substituted cyclohexyl, 2- or 3-substituted cyclopentyl, 4-substituted phenyl, 3,4-disubstituted phenyl, substituted thiophenyl, thiophenyl, biaryl, benzofuranyl, dihydrobenzofuranyl, 4-substituted pyridyl, benzo[b]thienyl, benzothiophenyl, indanyl, naphthyl, 5,6,7,8-tetrahydronapthyl, 1,2,3,4-tetrahydronaphthyl, or benzo[1,4]dioxan. 13. The method of claim 1, wherein Z is unsubstituted or substituted with between 1 and 2 substituents independently selected from methoxy, ethoxy, fluoro, chloro, methyl, ethyl, propyl, isopropyl, cyclopropyl, and phenyl. 14. The method of claim 1, wherein Z is biphenyl, 4-ethylphenyl, (4-propyl)phenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-methylthiophenyl, benzofuran-5-yl, dihydrobenzofuran-5-yl, naphthyl, or dihydrobenzofuran-6-yl, or (5-ethylthio)phenyl.