Use of (−) (3-trihalomethylphenoxy) (4-halophenyl) acetic acid derivatives for treatment of hyperuricemia
The present invention provides the use of (−)(3-trihalomethylphenoxy)(4-halophenyl)acetic acid derivatives and compositions in the treatment of insulin resistance, Type 2 diabetes, hyperlipidemia and hyperuricemia.
1. A method of treating hyperuricemia in a mammal, comprising administering to said mammal a therapeutically effective amount of the (−) stereoisomer of a compound of Formula I,
wherein:
R is a hydroxy group, a benzyloxy, phenethyloxy, formamidoethoxy, acetamidoethoxy, acetamidopropoxy, benzamidoethoxy, benzamidopropoxy, carbamoylmethoxy, carbamoylethoxy, 2-(4-chlorophenoxy)ethoxy, 2-(4-chlorophenoxy)-2-methylpropoxy or a 2-carbamoylphenoxy group forming an ester linkage capable of being hydrolyzed upon administration to the mammal to provide a compound of formula I wherein R is OH;
and
each X is independently a halogen; or
a pharmaceutically acceptable salt thereof,
wherein the compound contains the (−) stereoisomer in an enantiomeric excess of at least 80%.
2. The method of claim 1 , wherein the (−) stereoisomer of the compound is selected from the group consisting of (−) 2-acetamidoethyl 4-chlorophenyl-(3-trifluoromethylphenoxy)acetate and (−) 4-chlorophenyl-(3-trifluoromethylphenoxy)acetic acid and the pharmaceutically acceptable salts thereof.
3. The method of claim 2 , wherein the (−) stereoisomer of the compound is administered together with a pharmaceutically acceptable carrier.
4. The method of claim 2 , wherein the (−) stereoisomer is in an enantiomeric excess of at least 98%.
5. The method of claim 2 , wherein the compound is administered by an intravenous, transdermal, or oral route.
6. The method of claim 2 , wherein the amount administered is about 100 mg to about 3000 mg per day.
7. The method of claim 2 , wherein the amount administered is about 500 mg to about 1500 mg per day.
8. The method of claim 2 , wherein the amount administered is about 5 to about 250 mg per kg per day.
9. The method of claim 2 , wherein the enantiomeric excess is at least 96%.
10. The method of claim 2 , wherein the therapeutically effective amount is from 100 to 500 mg.
11. The method of claim 2 , wherein the therapeutically effective amount is from 500 to 1000 mg.
12. The method of claim 1 , wherein R is selected from the group consisting of benzyloxy, phenethyloxy, dimethyaminoethoxy, diethylaminopropoxy, benzamidoethoxy, benzamidopropoxy, carbamoylmethoxy, carbamoylethoxy, 2-(4-chlorophenoxy)ethoxy, 2-(4-chlorophenoxy)-2-methylpropoxy and 2-carbamoylphenoxy.
13. The method of claim 1 , wherein hydrolysis of the ester provides (−) 4-chlorophenyl-(3-trifluoromethylphenoxy)acetic acid.