Methods for treating liver disorders using fxr agonists

Abstract

The invention provides methods for modulating the activity of farnesoid X receptors (FXRs) using specific FXR agonists, in particular for treating or preventing liver diseases and disorders. In one embodiment, the invention provides a pharmaceutical unit dosage form composition, comprising a compound of Formula (I)or a stereoisomer, enantiomer or pharmaceutically acceptable salt thereof.

We claim: 
     
         1 . A pharmaceutical unit dosage form composition, comprising about 10 μg, about 30 μg, about 60 μg or about 90 μg of a compound of Formula (I) 
       
         
           
           
               
               
           
         
       
       or a stereoisomer, enantiomer or pharmaceutically acceptable salt thereof; suitable for oral administration up to a maximum total dose of 100 μg per day. 
     
     
         2 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 10 μg of said compound of Formula (I). 
     
     
         3 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 30 μg of said compound of Formula (I). 
     
     
         4 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 60 μg of a compound of Formula (I). 
     
     
         5 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 90 μg of a compound of Formula (I). 
     
     
         6 . The pharmaceutical unit dosage form composition of  claim 1 , wherein said compound of Formula (I) is 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The pharmaceutical unit dosage form composition of  claim 1 , wherein said compound of Formula (I) is 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid in free form. 
     
     
         8 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 10 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 10 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid in free form. 
     
     
         10 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 30 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 30 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid in free form. 
     
     
         12 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 80 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 80 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid in free form. 
     
     
         14 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 90 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The pharmaceutical unit dosage form composition of  claim 1 , comprising about 90 μg of 2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-8-carboxylic acid in free form.