Substituted indole-o-glucosides

Abstract

Substituted indole-O-glucosides, compositions containing them, and methods of using them, for example for the treatment of diabetes and Syndrome X are disclosed.

1 - 21 . (canceled) 
   
   
       22 . A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a mammal, said method comprising administering to a mammal in need of treatment an effective amount of 2-{3-[2-(2,3-Dihydro-benzofuran-5-yl)-ethyl]-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-{3-[2-(2,3-Dihydro-benzofuran-5-yl)-ethyl]-1-methyl-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-{3-[2-(4-Methoxy-phenyl)-ethyl]-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-6-O-methoxycarbonyl-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-6-O-ethoxycarbonyl-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-6-O-hexanoyl-β-D-glucopyranoside; 2-[3-(4-Methyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-(3-Biphenyl-4-ylmethyl-1H-indol-4-yloxy)-3-D-glucopyranoside; 2-[3-(4-Ethoxy-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Methylsulfanyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-6-methyl-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Thiophen-3-yl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; and 2-[3-(4-Pyridin-3-yl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; or a pharmaceutically acceptable salt thereof. 
   
   
       23 . The method of  claim 22 , wherein said diabetes is type II diabetes. 
   
   
       24 - 52 . (canceled) 
   
   
       53 . A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a mammal, said method comprising administering to a mammal in need of treatment an effective amount of a compound selected from the group consisting of 2-{3-[2-(2,3-Dihydro-benzofuran-5-yl)-ethyl]-1H-indol-4-yloxy}-6-O-acetyl-β-D-glucopyranoside; 2-[3-(2-Benzo[1,3]dioxol-5-yl-ethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-{3-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-ethyl]-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-[3-(2-Naphthalen-2-yl-ethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-{3-[2-(4-Ethoxy-phenyl)-ethyl]-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-{3-[2-(4-Methoxy-phenyl)-ethyl]-6-methyl-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-[3-(3-Fluoro-4-methyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Propyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Isopropyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(2-Fluoro-biphenyl-4-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Methoxy-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(3-Fluoro-4-methoxy-benzyl)-1H-indol-4-yloxy]-D-glucopyranoside; 2-[3-(4-Phenoxy-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Chloro-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-(3-Naphthalen-2-ylmethyl-1H-indol-4-yloxy)-β-D-glucopyranoside and 2-[3-(4-Ethyl-benzyl)-2-methyl-1H-indol-4-yloxy]-β-D-glucopyranoside; or a pharmaceutically acceptable salt thereof. 
   
   
       54 . The method of  claim 53 , wherein said diabetes is type II diabetes. 
   
   
       55 . A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a mammal, said method comprising administering to a mammal in need of treatment an effective amount of a compound selected from the group consisting of 2-{3-[2-(4-Ethyl-phenyl)-ethyl]-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-[1-Diethylcarbamoyl-3-(4-methoxy-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Methoxy-benzyl)-1-methyl-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1-isopropyl-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-Methyl-2-thienyl(−1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(2,3-Dihydro-benzofuran-5-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside and 2-[3-(4-Ethylbenzoyl)-1H-indol-4-yloxy]-β-D-glucopyranoside and 2-[3-(4-Methoxy-phenyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; or a pharmaceutically acceptable salt thereof. 
   
   
       56 . The method of  claim 55 , wherein said diabetes is type II diabetes. 
   
   
       57 . A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a mammal, said method comprising administering to a mammal in need of treatment an effective amount of a compound selected from the group consisting of 2-[3-(4-Cyclopropyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Pyrazol-1-yl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[6-Chloro-3-(4-ethyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-6-fluoro-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(5-Ethyl-thiophen-2-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(5-Propyl-thiophen-2-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; and 2-[3-(5-Phenyl-thiophen-2-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; or a pharmaceutically acceptable salt thereof. 
   
   
       58 . The method of  claim 57 , wherein said diabetes is type II diabetes. 
   
   
       59 . A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a mammal, said method comprising administering to a mammal in need of treatment an effective amount of a compound selected from the group consisting 2-{3-[2-(2,3-Dihydro-benzofuran-5-yl)-ethyl]-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-{3-[2-(2,3-Dihydro-benzofuran-5-yl)-ethyl]-1-methyl-1H-indol-4-yloxy}-β-D-glucopyranoside; 2-[3-(3-Fluoro-4-methyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Methylsulfanyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-6-methyl-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Methyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-6-O-methoxycarbonyl-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-6-O-ethoxycarbonyl-β-D-glucopyranoside; 2-[3-(4-Propyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-(3-(4-Thiophen-3-yl-benzyl)-1H-indol-4-yloxy)-β-D-glucopyranoside; 2-[3-(4-Cyclopropyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Pyrazol-1-yl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside, 2-[6-Chloro-3-(4-ethyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-6-fluoro-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(5-Ethyl-thiophen-2-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside and 2-[3-(5-Phenyl-thiophen-2-ylmethyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; or a pharmaceutically acceptable salt thereof. 
   
   
       60 . The method of  claim 59 , wherein said diabetes is type II diabetes. 
   
   
       61 . A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a mammal, said method comprising administering to a mammal in need of treatment an effective amount of a compound selected from the group consisting 2-{3-[2-(2,3-Dihydro-benzofuran-5-yl)-ethyl]-1H-indol-4-yloxy}β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-β-D-glucopyranoside; 2-[3-(4-Ethyl-benzyl)-1H-indol-4-yloxy]-6-O-ethoxycarbonyl-β-D-glucopyranoside; and 2-(3-(4-Thiophen-3-yl-benzyl)-1H-indol-4-yloxy)-β-D-glucopyranoside; or a pharmaceutically acceptable salt thereof. 
   
   
       62 . The method of  claim 61 , wherein said diabetes is type II diabetes.