Thyroid hormone analogs
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto.
1. A compound of the formula (I):
wherein:
A is O, CH 2 , S, SO or SO 2 ;
X and Y are each independently selected from the group consisting of Br, Cl and —CH 3 ;
R 1 is selected from the group consisting of —(CH 2 ) n COOH, —OCH 2 COOH, —NHC(═O)COOH, —NHCH 2 COOH, —NHC(═O)COONH 2 and
R 2 is lower alkyl;
R 3 is H or lower alkyl;
n is 1, 2 or 3;
p is 1 or 2;
or a pharmaceutically acceptable salt or ester thereof.
2. The compound according to claim 1 , wherein X and Y are each Br.
3. The compound according to claim 1 , wherein X and Y are each Cl.
4. The compound according to claim 1 , wherein X and Y are each —CH 3 .
5. The compound according to claim 1 , wherein X is Cl, and Y is —CH 3 .
6. The compound according to claim 1 , wherein R 1 is selected from the group consisting of —(CH 2 ) n COOH, —OCH 2 COOH, —NHC(═O)COOH, and —NHCH 2 COOH;
and esters thereof.
7. The compound according to claim 6 , wherein R 1 is —(CH 2 ) n COOH.
8. The compound according to claim 7 , wherein n is 1.
9. The compound according to claim 6 , wherein R 1 is —NHC(═O)COOH.
10. The compound according to claim 1 , wherein R 1 is:
11. The compound according to claim 1 , wherein R 2 is lower alkyl having from 1 to 3 C atoms.
12. The compound according to claim 11 , wherein R 2 is lower alkyl having 3 C atoms.
13. The compound according to claim 1 , wherein R 3 is CH 3 .
14. The compound according to claim 1 , which is
or a pharmaceutically acceptable salt or ester thereof.
15. The compound according to claim 1 , which is
or a pharmaceutically acceptable salt thereof.
16. The compound according to claim 1 , which is
or a pharmaceutically acceptable salt or ester thereof.
17. The compound according to claim 1 , which is
or a pharmaceutically acceptable salt or ester thereof.
18. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
19. A compound, which is:
or a pharmaceutically acceptable salt thereof.