Linked biaryl compounds

1. A compound having the formula (Ia):

R 1 O 2 C—CR a R b —Y—Ar 1 —X—Ar 2 —Z 1 —Z 2 —Ar 3   Ia

or a pharmaceutically acceptable salt or prodrug thereof, wherein

X is selected from the group consisting of S(O) m , CR′R″ and SO 2 NR″;

Y is O or CR′R″;

Z 1 and Z 2 are independently selected from the group consisting of O, S(O) m , (CR′R″) n , N(R″), C(O)NR″ and CR′R″C(O)NR′″;

alternatively, Z 1 and Z 2 may be combined to form (C 2 -C 4 )alkenyl;

Ar 1 and Ar 2 are independently an aromatic group;

Ar 3 is aryl;

R 1 is selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl and aryl(C 1 -C 4 )alkyl;

R a and R b are independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, aryl and aryl(C 1 -C 4 )alkyl;

each R′, R″ and R′″ is independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, aryl and aryl(C 1 -C 4 )alkyl;

the subscript m is an integer from 0 to 2; and

the subscript n is an integer from 1 to 2.

2. A compound having the formula_(Ia):

R 1 O 2 C—CR a R b —Y—Ar 1 —X—Ar 2 —Z 1 —Z 2 —Ar 3   Ia

or a pharmaceutically acceptable salt or prodrug thereof, wherein

X is S;

Y is O;

Z 1 is (CR′R″) n ;

Z 2 is O;

Ar 1 and Ar 2 are independently phenyl;

Ar 3 is phenyl; and

R 1 is selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl and aryl(C 1 -C 4 )alkyl;

R a and R b are independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, aryl and aryl(C 1 -C 4 )alkyl;

each R′ and R″ and is independently selected from the group, consisting of hydrogen, (C 1 -C 4 )alkyl, aryl and aryl(C 1 -C 4 )alkyl; and

the subscript n is an integer from 1 to 2.

3. The compound of claim 2 , having the formula (Ib):

wherein

R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen, (C 1 -C 4 )alkyl, (C 5 -C 6 )cycloalkyl, fluoro(C 1 -C 4 )alkyl, OR′, aryl, aryl(C 1 -C 4 )alkyl, NO 2 , NR′R″, C(O)R′, CO 2 R, C(O)NR′R″, N(R″)C(O)R′, N(R″)CO 2 R′, N(R″)C(O)NR′R″, S(O) m NR′R″, S(O) m R′, CN and N(R″)S(O) m R′;

optionally, when R′ and R″ are attached to the same nitrogen atom, R′ and R″ may be combined with the nitrogen atom to form a 5-, 6- or 7-membered ring containing from 1 to 3 heteroatoms selected from the group consisting of N, O and S; and

optionally, any two adjacent R groups selected from the group consisting of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 may be combined with the carbon atoms to which they are attached to form a fused aromatic or cycloalkane ring.

4. The compound of claim 3 , wherein R a and R b are both hydrogen or methyl.

5. The compound of claim 3 , having the formula (II):

wherein

R 1′ , R 2′ , R 3′ , R 4′ and R 5′ are independently selected from the group consisting of hydrogen, halogen, (C 1 -C 4 )alkyl, fluoro(C 1 -C 4 )alkyl, OR′, aryl, aryl(C 1 -C 4 )alkyl, NO 2 , NR′R″, C(O)R′, CO 2 R′, C(O)NR′R″, N(R″)C(O)R′, N(R″)CO 2 R′, N(R″)C(O)NR′R″, S(O) m NR′R″, S(O) m R′, CN and N(R″)S(O) m R′.

6. The compound of claim 5 , wherein at least one of R 1′ , R 2′ , R 3′ , R 4′ and R 5′ is not hydrogen.

7. The compound of claim 5 , wherein at least one of R 1′ , R 2′ , R 3′ , R 4′ and R 5′ 0 is fluoro(C 1 -C 4 )alkyl.

8. The compound of claim 7 , wherein R 3′ is CF 3 .

9. The compound of claim 7 , wherein R 4′ is CF 3 .

10. The compound of claim 7 , wherein R 5′ is CF 3 .

11. The compound of claim 3 , wherein Z 1 is CH 2 .

12. The compound of claim 2 , or a pharmaceutically acceptable salt or prodrug thereof, wherein said compound is selected from the group consisting of:

13. The compound of claim 3 , wherein

R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen and (C 1 -C 4 )alkyl and (C 5 -C 6 )cycloalkyl;

optionally, any two adjacent R groups selected from the group consisting of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 may be combined with the carbon atoms to which they are attached to form a fused benzene or cyclohexane ring; and

R a and R b are hydrogen.

14. The compound of claim 3 , wherein

R 1 is hydrogen;

R 2 , R 3 , R 4 , R 6 and R 7 are independently selected from the group consisting of hydrogen, chlorine, methyl, ethyl, n-propyl, isopropyl and cyclopentyl;

optionally, R 2 and R 3 are combined with the carbon atoms to which they are attached to form a fused benzene or cyclohexane ring;

optionally, R 6 and R 7 are combined with the carbon atoms to which they are attached to form a fused benzene ring;

R 5 , R 8 and R 9 are each hydrogen; and

R a and R b are hydrogen.

15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, excipient, or diluent and a compound according to claim 1 .

16. A method for treating a metabolic disorder disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1 (having the formula (Ia).

17. The method of claim 16 , wherein said metabolic disorder is selected from the group consisting of hypercholesterolemia, hyperlipidemia, dyslipidemia, hypertriglylceridemia, hyperglycemia, diabetes, obesity, syndrome X, insulin resistance, hyperinsulinemia and an eating disorder.

18. The method of claim 16 , wherein the subject is a human.

19. The compound of claim 12 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

20. The pharmaceutical composition of claim 15 wherein

X is S;

Y is O;

Z 1 is (CR′R″) n ;

Z 2 is O;

Ar 1 and Ar 2 are independently phenyl; and

Ar 3 is phenyl.

21. The pharmaceutical composition of claim 15 wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt or prodrug thereof.

22. The pharmaceutical composition according to claim 15 comprising a compound having the formula (Ia), or a pharmaceutically acceptable salt thereof.

23. The pharmaceutical composition of claim 21 wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

24. The method of claim 16 wherein the compound has formula (Ia), or a pharmaceutically acceptable salt thereof.

25. The method of claim 16 wherein

X is S;

Y is O;

Z 1 is (CR′R″) n ;

Z 2 is O;

Ar 1 and Ar 2 are independently phenyl; and

Ar 3 is phenyl.

26. The method of claim 16 wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt or prodrug thereof.

27. The method of claim 26 , wherein the subject is a human.

28. The method of claim 26 wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.