Use of (−)(3-trihalomethylphenoxy)(4-halophenyl) acetic acid derivatives for treatment of type 2 diabetes
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 and hyperlipidemia.
1. A method of treating Type 2 diabetes 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 in vivo to provide a compound of formula I wherein R is OH;
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 compound is (−) 2-acetamidoethyl 4-chlorophenyl-(3-trifluoromethylphenoxy) acetate or 4-chlorophenyl-(3-trifluoromethylphenoxy) acetic acid or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 , wherein the compound is administered by an intravenous, transdermal, or oral route.
4. The method of claim 2 , wherein the amount administered is about 100 mg to about 3000 mg per day.
5. The method of claim 2 , wherein the amount administered is about 500 mg to about 1500 mg per day.
6. The method of claim 2 , wherein the amount administered is about 5 to about 250 mg per kg per day.
7. The method of claim 2 , wherein the compound is administered together with a pharmaceutically acceptable carrier.
8. The method of claim 2 , wherein the (−) stereoisomer is in an enantiomeric excess of at least 98%.
9. The method of claim 2 , wherein the enantiomeric excess is at least 96%.
10. The method of claim 1 , 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 the therapeutically effective amount is from 500 to 1500 mg.
13. The method of claim 1 , wherein R is a formamidoethoxy, acetamidoethoxy, acetamidopropoxy, benzamidoethoxy or a benzamidopropoxy group.
14. The method of claim 1 , wherein hydrolysis of the ester provides (−) 4-chlorophenyl-(3-trifluoromethylphenoxy) acetic acid.