Thyroid hormone β receptor agonist

1. A compound represented by the formula:

wherein

A is optionally substituted alkyl, optionally substituted carbocyclic group, optionally substituted aryl, optionally substituted heterocyclic group, optionally substituted heteroaryl, optionally substituted amino, or optionally substituted carbamoyl,

X is optionally substituted methylene, —O— or —S—,

Q is C—R 4 ,

L 1 is single bond, methylene, —CH═CH—, —O—, —CO—, —NR 11 —, —NR 11 CO—, —CONR 11 —, —CH 2 NR 11 — or —S—,

L 2 is single bond, —CR 6 R 7 —, or divalent heterocyclic group,

R 1 and R 2 are the same or different and each is hydrogen, alkyl, alkenyl or halogen,

R 3 and R 4 are the same or different and each is hydrogen, alkyl, alkoxy, cyano or halogen,

R 1 and R 3 are optionally bonded to form carbocycle or heterocycle,

R 5 is a carboxyl group, an alkoxycarbonyl group or bioisosteric group of carboxyl group, wherein the bioisosteric group is selected from the group consisting of the following formulae:

wherein R 51 and R 52 are the same or different and each is alkyl optionally substituted by alkanoyloxy or alkoxycarbonyl, or hydrogen, R 51 and R 52 may be bonded to form heterocycle optionally substituted by aryl optionally substituted by halogen, and R 53 and R 54 are the same or different and each is alkyl or hydrogen,

R 6 and R 7 are the same or different and each is hydrogen, optionally substituted alkyl or halogen, or

R 6 and R 7 are bonded to form cycloalkane or heterocycle,

R 8 is hydroxy, alkanoylamino or alkylsulfonylamino,

R 9 and R 10 are the same or different and each is hydrogen, alkyl or halogen, and

R 11 is hydrogen or alkyl,

or a pharmacologically acceptable salt thereof.

2. The compound according to claim 1 , wherein the substituent of the optionally substituted alkyl for A is the same or different 1-3 groups selected from

aryl optionally substituted by 1-3 groups selected from alkyl, halogen, alkoxy, alkanoyl, and cyano;

a heterocyclic group optionally substituted by 1-3 groups selected from alkyl, halogen, alkoxy, alkanoyl, and cyano;

heteroaryl optionally substituted by 1-3 groups selected from alkyl, halogen, alkoxy, alkanoyl, and cyano;

cycloalkyl optionally substituted by 1-3 groups selected from alkyl, halogen, alkoxy, alkanoyl, and cyano;

hydroxy;

alkoxy;

halogen;

amino group optionally substituted by 1 or 2 alkyl; and

oxo,

the substituent of the optionally substituted aryl, optionally substituted carbocyclic group, optionally substituted heterocyclic group and optionally substituted heteroaryl group for A is the same or different 1-3 groups selected from

alkyl optionally substituted by hydroxy, alkoxy, cycloalkyl or halogen;

alkenyl optionally substituted by alkoxy or cycloalkyl;

cycloalkyl optionally substituted by alkyl, alkoxy or cycloalkyl;

alkoxy optionally substituted by alkoxy, cycloalkyl or halogen;

cycloalkyloxy optionally substituted by alkyl, alkoxy or cycloalkyl;

halogen;

cyano;

hydroxy;

oxo;

heterocycle;

alkylsulfonyl; and

mono or dialkylcarbamoyl,

the substituent of the optionally substituted amino for A is the same or different 1 or 2 alkyl optionally substituted by alkoxy, cycloalkyl or halogen;

alkenyl optionally substituted by alkoxy or cycloalkyl;

cycloalkyl optionally substituted by alkyl, alkoxy or cycloalkyl;

alkanoyl optionally substituted by alkoxy, cycloalkyl or halogen; or

aryl optionally substituted by alkyl, alkoxy or cycloalkyl,

the substituent of the optionally substituted carbamoyl for A is the same or different 1 or 2 alkyl optionally substituted by aryl,

the substituent of the optionally substituted alkyl for R 6 or R 7 is alkoxy, hydroxy or halogen, and

the substituent of the optionally substituted methylene for X is alkoxy or hydroxy, or a pharmacologically acceptable salt thereof.

3. The compound according to claim 2 , wherein A is optionally substituted alkyl, optionally substituted carbocyclic group, optionally substituted aryl, optionally substituted heterocyclic group or optionally substituted heteroaryl,

Q is C—R 4 ,

R 1 and R 2 are the same or different and each is alkyl or halogen,

R 3 and R 4 are the same or different and each is hydrogen, alkyl or halogen,

X is methylene, —O— or —S—,

R 5 is a carboxyl group, an alkoxycarbonyl group, or bioisosteric group of carboxyl group, wherein the bioisosteric group is selected from the group consisting of the following formulae:

wherein R 51 and R 52 are the same or different and each is alkyl optionally substituted by alkanoyloxy or alkoxycarbonyl, or hydrogen, R 51 and R 52 may be bonded to form heterocycle optionally substituted by aryl optionally substituted by halogen, and R 53 and R 54 are the same or different and each is alkyl or hydrogen,

L 1 is a single bond, methylene, —CH═CH—, —O—, —NH—, —NHCO— or —S—,

L 2 is a single bond, —CR 6 R 7 —, or divalent heterocyclic group,

R 6 and R 7 are the same or different and each is hydrogen, alkyl or halogen, or R 6 and R 7 are bonded to form cycloalkane or heterocycle together with the adjacent carbon,

R 8 is hydroxy, and

R 9 and R 10 are hydrogen, or a pharmacologically acceptable salt thereof.

4. The compound according to claim 1 , wherein A is an optionally substituted carbocyclic group, or a pharmacologically acceptable salt thereof.

5. The compound according to claim 1 , wherein A is optionally substituted aryl, or a pharmacologically acceptable salt thereof.

6. The compound according to claim 4 , wherein the optionally substituted carbocyclic group is optionally substituted cycloalkyl, or a pharmacologically acceptable salt thereof.

7. The compound according to claim 1 , wherein A is optionally substituted alkyl, or a pharmacologically acceptable salt thereof.

8. The compound according to claim 1 , wherein A is optionally substituted heterocyclic group, or a pharmacologically acceptable salt thereof.

9. The compound according to claim 1 , wherein A is optionally substituted heteroaryl, or a pharmacologically acceptable salt thereof.

10. The compound according to claim 1 , wherein X is methylene, or a pharmacologically acceptable salt thereof.

11. The compound according to claim 1 , wherein R 1 and R 2 are the same group, or a pharmacologically acceptable salt thereof.

12. The compound according to claim 1 , wherein R 1 and R 2 are the same or different and each is alkyl, or a pharmacologically acceptable salt thereof.

13. The compound according to claim 1 , wherein R 1 and R 3 are bonded to form carbocycle or heterocycle, or a pharmacologically acceptable salt thereof.

14. The compound according to claim 1 , wherein R 8 is hydroxy, or a pharmacologically acceptable salt thereof.

15. (4-{[5-Hydroxy-6-(2-naphthyl)pyridin-2-yl]methyl}-3,5-dimethylphenoxy)acetic acid;

{4-[(6-cyclopentyl-5-hydroxypyridin-2-yl)methyl]-2,3,5-trimethylphenoxy}acetic acid;

{4-[(6-cyclohexyl-5-hydroxypyridin-2-yl)methyl]-2,3,5-trimethylphenoxy}acetic acid;

{2-bromo-4- [(6-cyclohexyl-5-hydroxypyridin-2-yl)methyl]-3,5-dimethylphenoxy}acetic acid;

3-({4-[(5-hydroxy-6-phenylpyridin-2-yl)methyl]-3,5-dimethylphenyl}amino)-3-oxopropanoic acid;

3-({4-[(6-cyclohexyl-5-hydroxypyridin-2-yl)methyl]-3,5-dimethylphenyl}amino)-3-oxopropanoic acid;

3-[(4-{[5-hydroxy-6-(2-naphthyl)pyridin-2-yl]methyl}-3,5-dimethylphenoxy)methyl]-1,2,4-oxadiazol-5(4H)-one;

3-[(4- {[5-hydroxy-6-(5,6,7,8-tetrahydronaphthalen-2-yl)pyridin-2-yl]methyl }-3,5-dimethylphenoxy)methyl]-1,2,4-oxadiazol-5(4H)-one;

3-({4-[(6-cycloheptyl-5-hydroxypyridin-2-yl)methyl]-3,5-dimethylphenyl}amino)-3-oxopropanoic acid;

N-[2-chloro-4-(6-cyclohexyl-5-hydroxy-pyridin-2-ylmethyl)-3,5-dimethyl-phenyl]amino-3-oxopropanoic acid;

3-[(2-fluoro-4-{[6-(2-fluoro-3-methylphenyl)-5-hydroxypyridin-2-yl]methyl}-3,5-dimethylphenoxy)methyl]-1,2,4-oxadiazol-5(4H)-one;

{4-[(6-cyclohexyl-4-fluoro-5-hydroxypyridin-2-yl)methyl]-2,3,5-trimethylphenoxy}acetic acid;

{4-[(6-cyclohexyl-3-fluoro-5-hydroxypyridin-2-yl)methyl]-2,3,5-trimethylphenoxy}acetic acid;

{4-[(6-cycloheptyl-5-hydroxypyridin-2-yl)methyl]-2,3,5-trimethylphenoxy}acetic acid;

3-({4-[(6-cycloheptyl-5-hydroxypyridin-2-yl)methyl]-2-fluoro-3,5-dimethylphenyl}amino)-3-oxopropanoic acid;

{4-[6-(3-fluoro-phenyl)-5-hydroxy-pyridin-2-ylmethyl]-2,3,5-trimethyl-phenoxy}acetic acid;

(4-{[6-(3-chlorophenyl)-5-hydroxypyridin-2-yl]methyl}-2,3,5-trimethylphenoxy)acetic acid;

3-{2-fluoro-4-[5-hydroxy-6-(2,3,4-trifluoro-phenyl)-pyridin-2-ylmethyl]-3,5-dimethyl-phenoxymethyl}-1,2,4-oxadiazol-5(4H)-one;

3-[(2-fluoro-4-{[5-hydroxy-6-(3-pyrrolidin-1-ylphenyl)pyridin-2-yl]methyl}-3,5-dimethylphenoxy)methyl]-1,2,4-oxadiazol-5(4H)-one;

2-{4-[(5-hydroxy-6-phenylpyridin-2-yl)methyl]-3,5-dimethylphenyl}-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile;

3-{2-fluoro-4-[5-hydroxy-6-(3-propoxy-phenyl)-pyridin-2-ylmethyl]-3,5-dimethyl-phenoxymethyl}-1,2,4-oxadiazol-5(4H)-one;

[3,5-dibromo-2-fluoro-4-(5-hydroxy-6-phenyl-pyridin-2-ylmethyl)-phenoxy]acetic acid;

(5-ethyl-4-{[6-(3-fluorophenyl)-5-hydroxypyridin-2-yl]methyl}-2,3-dimethylphenoxy)acetic acid, or a pharmacologically acceptable salt thereof.

16. A pharmaceutical composition comprising:

the compound according to claim 1 , or a pharmacologically acceptable salt thereof, as an active ingredient; and

a pharmaceutically acceptable carrier.

17. The compound according to claim 3 , wherein X is methylene, and R 8 is hydroxyl, or a pharmacologically acceptable salt thereof.

18. The compound according to claim 17 , wherein -L 1 -L 2 -L 5 is Selected from the group consisting of the following formulae:

or a pahramacologically acceptable salt thereof.

19. The compound according to claim 18 , wherein A is optionally substituted cycloalkyl, or a pharmacologically acceptable salt thereof.