Bile acid derivatives as FXR ligands for the prevention or treatment of FXR-mediated diseases or conditions
The present invention relates to compounds of formula (I): wherein R is hydrogen or alpha-hydroxy, the hydroxyl group in position 7 is in the alpha or beta position; and pharmaceutically acceptable salts, solvates or amino acid conjugates thereof.
1. A compound selected from
2. A method for treating an FXR-mediated disease or condition in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of claim 1 , wherein the FXR-mediated disease or condition is selected from:
cholestasis;
colitis;
a chronic liver disease selected from primary biliary cirrhosis, primary sclerosing cholangitis, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis,
a gastrointestinal disease selected from inflammatory bowel disease, irritable bowel syndrome, bacterial overgrowth, and malabsorption;
a renal disease selected from diabetic nephropathy, focal segmental glomerulosclerosis, and chronic glomerulonephritis;
a cardiovascular disease selected from atherosclerosis, arteriosclerosis, dyslipidemia, hypercholesterolemia, and hypertriglyceridemia; and
a metabolic disease selected from insulin resistance, Type I and Type II diabetes, and obesity.
3. The method of claim 2 , wherein the FXR-mediated disease or condition is cholestasis.
4. The method of claim 2 , wherein the FXR-mediated disease or condition is a chronic liver disease.
5. The method of claim 2 , wherein the FXR-mediated disease or condition is a gastrointestinal disease.
6. The method of claim 2 , wherein the FXR-mediated disease or condition is a renal disease.
7. The method of claim 2 , wherein the FXR-mediated disease or condition is a cardiovascular disease.
8. The method of claim 2 , wherein the FXR-mediated disease or condition is a metabolic disease.
9. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.