Bisaryl-sulfonamides
View Patent ↗Bisaryl-sulfonamide compounds having the formula wherein Ar, R 1 , R 2 , L, B, W, X, Y, and Z, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by PPARγ or PPARδ. In particular, the compounds of the invention modulate the function of PPARγ or PPARδ. The subject methods are particularly useful in the treatment and/or prevention of diabetes, obesity, hypercholesterolemia, rheumatoid arthritis and atherosclerosis.
1. A compound having the formula (I):
wherein
Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl; each of which is optionally substituted with from one to three R 8 substituents, wherein each R 8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )haloalkyl, (C 1 -C 8 )haloalkoxy, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, hydroxyl and NR 12 R 13 ;
B is aryl or heteroaryl; each of which is optionally substituted with from one to two R 9 substituents, wherein each R 9 is a member independently selected from the group consisting of halogen, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy and NR 12 R 13 ;
L is selected from the group consisting of O, S(O) k , CR a R b and C(O);
each R a or R b is independently selected from the group consisting of hydrogen, cyano, nitro, and (C 1 -C 8 )alkyl;
W is independently C(R 3 ) or N;
X is independently C(R 4 ) or N;
Y is independently C(R 5 ) or N;
Z is independently C(R 6 ) or N, wherein one of W, X, Y and Z is N and three of W, X, Y and Z are other than N;
R 1 is selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )heteroalkyl and aryl(C 1 -C 8 )alkyl;
R 2 is S(O) m R 7 ;
each R 3 , R 4 , R 5 , or R 6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR 12 R 13 , (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, hydroxy(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )thioalkoxy, (C 2 -C 8 )heteroalkyl, aryl, heteroaryl, —C(O)R 11 , —CO 2 R 11 , —C(O)N R 12 R 13 , —C(O )CH 2 CN, —X 1 Q 1 , X 2 OR 11 and X 2 NR 12 R 13 ;
each X 1 is independently selected from the group consisting of (C 1 -C 2 )alkylene and C(O); and
each Q 1 is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl, aryl, NR 12 R 13 , (C 3 -C 8 )heterocycloalkyl, X 2 —C(O)OR 15 , X 2 —C(O)N(R 15 ) 2 , and —X 2 —R 12 R 13 ;
each X 2 is (C 1 -C 8 )alkylene;
each R 11 is independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, aryl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, (C 3 -C 8 )heterocycloalkyl and aryl(C 1 -C 8 )alkyl;
each R 12 and R 13 is independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, (C 1 -C 8 )alkoxy, aryl and aryl(C 1 -C 8 )alkyl;
optionally, R 12 and R 13 are combined with the nitrogen to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S; wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C 1 -C 8 )alkyl;
each R 15 is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 3 -C 8 )cycloalkyl; and
the subscripts k and m are independently an integer of 0 to 2.
2. The compound of claim 1 , wherein Ar is phenyl, optionally substituted with from one to three R 8 substitutents, wherein each R 8 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy, and (C 1 -C 8 )haloalkyl.
3. The compound of claim 1 , wherein R 1 is H.
4. The compound of claim 1 , wherein W is N; X is C(R 4 ); Y is C(R 5 ); and Z is C(R 6 ).
5. The compound of claim 1 , wherein W is C(R 3 ); Y is C(R 5 ); Z is C(R 6 ); and X is N.
6. The compound of claim 1 , wherein each R 3 , R 4 , R 5 , or R 6 is independently selected from the group consisting of hydrogen, hydroxy, halogen, NR 12 R 13 , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )thioalkoxy, (C 2 -C C 8 )heteroalkyl, (C 2 -C 8 )haloalkyl, CN, —C(O)R 11 , —CO 2 R 11 and —C(O)NR 12 R 13 .
7. The compound of claim 1 , wherein L is O.
8. The compound of claim 1 , wherein L is S.
9. The compound of claim 1 , wherein B is aryl, which is optionally substituted with from one to two R 9 substituents.
10. The compound of claim 9 , wherein B is phenyl or naphthyl, each of which is optionally substituted with from one to two R 9 substituents.
11. The compound of claim 10 , wherein B is phenyl, which is optionally substituted with from one to two R 9 substituents.
12. The compound of claim 1 , wherein B is heteroaryl, which is optionally substituted with from one to two R 9 substituents.
13. The compound of claim 1 , wherein B is benzothiazolyl, which is optionally substituted with from one to two R 9 substituents.
14. The compound of claim 1 wherein R 2 is SO 2 R 7 .
15. The compound of claim 14 , wherein R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, NR 12 R 13 and (C 3 -C 8 )heterocycloalkyl.
16. The compound of claim 15 , wherein R 7 is selected from the group consisting of cyclopentyl, cyclohexyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, and azepinyl.
17. The compound of claim 15 , wherein R 7 is selected from the group consisting of
wherein
Q is N or CH;
T is CHR 16 , NR 16 , O, or S(O) 1 ;
R 16 is H or (C 1 -C 8 )alkyl;
each R 23 is a member independently selected from the group consisting of H and (C 1 -C 8 )alkyl;
each R 24 is selected from the group consisting of H, (C 1 -C 8 )alkyl and heteroalkyl; and
the subscript 1 is an integer of from 0 to 2.
18. The compound of claim 15 , wherein R 7 is X 2 —C(O)OR 15 or X 2 —C(O)N(R 15 ) 2 ; and
each R 15 is H or (C 1 -C 8 )alkyl.
19. A compound having a formula selected from the group consisting of:
wherein
Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl; each of which is optionally substituted with from one to three R 8 substituents, wherein each R 8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )haloalkyl, (C 1 -C 8 )haloalkoxy, (C 2 -C 8 )alkenyl, (C 2 -C- 8 )alkynyl, hydroxyl and NR 12 R 13 ;
B is aryl or heteroaryl; each of which is optionally substituted with from one to two R 9 substituents, wherein each R 9 is a member independently selected from the group consisting of halogen, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy and NR 12 R 13 ;
L is selected from the group consisting of O, S(O) k , CR a R b and C(O);
each R a or R b is independently selected from the group consisting of hydrogen, cyano, nitro, and (C 1 -C 8 )alkyl;
R 1 is selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C C 8 )heteroalkyl and aryl(C 1 -C 8 )alkyl;
R 2 is S(O) m R 7 ;
each R 3 , R 4 , R 5 , or R 6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR 12 R 13 , (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, hydroxy(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )thioalkoxy, (C 2 -C 8 )heteroalkyl, aryl, heteroaryl, —C(O)R 11 , —CO 2 R 11 , —C(O)N R 12 R 13 , —C(O)CH 2 CN, —X 1 Q 1 , X 2 OR 11 and X 2 NR 12 R 13 ;
each X 1 is independently selected from the group consisting of (C 1 -C 2 )alkylene and C(O); and
each Q 1 is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl, aryl, NR 12 R 13 , (C 3 -C 8 )heterocycloalkyl, X 2 —C(O)OR 15 , X 2 —C(O)N(R 15 ) 2 , and —X 2 —NR 12 R 13 ;
each X 2 is (C 1 -C 8 )alkylene;
each R 11 is independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, aryl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, (C 3 -C 8 )heterocycloalkyl and aryl(C 1 -C 8 )alkyl;
R 12 and R 13 are independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, (C 1 -C 8 )alkoxy, aryl and aryl(C 1 -C 8 )alkyl;
optionally, R 12 and R 13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S; wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C 1 -C 8 )alkyl;
each R 15 is selected from the group consisting of H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 3 -C 8 )cycloalkyl; and
the subscripts k and m are independently an integer of 0 to 2.
20. The compound of claim 19 , wherein Ar is phenyl, optionally substituted with from one to three R 8 substitutents, wherein each R 8 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy, and (C 1 -C 8 )haloalkyl.
21. The compound of claim 19 , wherein R 1 is H.
22. The compound of claim 19 , wherein each R 3 , R 4 , R 5 , or R 6 is independently selected from the group consisting of hydrogen, hydroxy, halogen, NR 12 R 13 , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )thioalkoxy, (C 2 -C 8 )heteroalkyl, (C 1 -C 8 )haloalkyl, CN, —C(O) 11 , —CO 2 R 11 and —C(O)NR 12 R 13 .
23. The compound of claim 19 , wherein L is O.
24. The compound of claim 19 , wherein L is S.
25. The compound of claim 19 , wherein B is aryl; optionally substituted with from one to two R 9 substituents.
26. The compound of claim 25 , wherein B is selected from the group consisting of phenyl and naphthyl; optionally substituted with from one to two R 9 substituents.
27. The compound of claim 26 , wherein B is phenyl; optionally substituted with from one to two R 9 substituents.
28. The compound of claim 19 , wherein B is heteroaryl; optionally substituted with from one to two R 9 substituents.
29. The compound of claim 28 , wherein B is benzothiazolyl; optionally substituted with from one to two R 9 substituents.
30. The compound of claim 19 , wherein R 2 is SO 2 R 7 .
31. The compound of claim 30 , wherein R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, NR 12 R 13 , and (C 3 -C 8 )heterocycloalkyl.
32. The compound of claim 31 , wherein R 7 is selected from the group consisting of
wherein
Q is N or CH;
T is CHR 16 , NR 16 , O, or S(O) 1 ;
R 16 is H or (C 1 -C 8 )alkyl;
each R 23 is a member independently selected from the group consisting of H and (C 1 -C 8 )alkyl;
each R 24 is selected from the group consisting of H, (C 1 -C 8 )alkyl and heteroalkyl; and
1 is an integer of from 0 to 2.
33. The compound of claim 31 , wherein R 7 is selected from the group consisting of cyclopentyl, cyclohexyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, and azepinyl.
34. The compound of claim 30 , wherein
R 7 is X 2 —C(O)OR 15 , X 2 —C(O)N(R 15 ) 2 ; and
each R 15 is H or (C 1 -C 8 )alkyl.
35. A compound having the formula (VIII):
or a pharmaceutically acceptable salt thereof, wherein
Ar is a member selected from the group consisting of phenyl, naphthyl and pyridyl; each of which is optionally substituted with from one to three R 8 substituents, wherein each R 8 is a member independently selected from the group consisting of halogen, cyano, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )haloalkyl, (C 1 -C 8 )haloalkoxy, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, hydroxyl and NR 12 R 13 ;
L is selected from the group consisting of O, S(O) k , CR a R b and C(O);
each R a or R b is independently selected from the group consisting of hydrogen, cyano, nitro, and (C 1 -C 8 )alkyl;
W is independently C(R 3 ) or N;
X is independently C(R 4 ) or N;
Y is independently C(R 5 ) or N;
Z is independently C(R 6 ) or N, wherein one of W, X, Y and Z is N and three of W, X, Y and Z are other than N;
each R 3 , R 4 , R 5 , or R 6 is a member independently selected from the group consisting of hydrogen, hydroxy, halogen, cyano, nitro, NR 12 R 13 , (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl, hydroxy(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )thioalkoxy, (C 2 -C 8 )heteroalkyl, heteroaryl, —C(O)R 11 , —CO 2 R 11 , —C(O)NR 12 R 13 , —C(O)CH 2 CN, —X 1 Q 1 , X 2 OR 11 and X 2 NR 12 R 13 ;
each X 1 is independently selected from the group consisting of (C 1 -C 2 )alkylene and C(O);
each Q 1 is independently selected from the group consisting of pyrrolidinyl, piperidinyl, and morpholinyl;
R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl, aryl, NR 12 R 13 , (C 3 -C 8 )heterocycloalkyl, X 2 —C(O)OR 15 , X 2 —C(O)N(R 15 ) 2 , and —X 2 —NR 12 R 13 ;
each X 2 is (C 1 -C 8 )alkylene;
each R 9 is a member independently selected from the group consisting of halogen, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy and NR 12 R 13 ;
each R 11 is independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, aryl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, (C 3 -C 8 )heterocycloalkyl and aryl(C 1 -C 8 )alkyl;
R 12 and R 13 are independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, (C 1 -C 8 )alkoxy, aryl and aryl(C 1 -C 8 )alkyl;
optionally, R 12 and R 13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S; wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C 1 -C 8 )alkyl;
each R 15 is selected from the group consisting of H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 3 -C 8 )cycloalkyl; and
the subscripts k, l, m, and q are independently an integer of 0 to 2.
36. The compound of claim 35 , wherein Ar is phenyl, which is optionally substituted with from one to three R 8 substituents, wherein each R 8 is independently selected from the group consisting of halogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy, and (C 1 -C 8 )haloalkyl.
37. The compound of claim 35 , wherein R 1 is H.
38. The compound of claim 35 , wherein each R 3 , R 4 , R 5 , or R 6 is independently selected from the group consisting of hydrogen, hydroxy, halogen, NR 12 R 13 , (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkoxy, (C 1 -C 8 )thioalkoxy, (C 2 -C 8 )heteroalkyl, (C 1 -C 8 )haloalkyl, CN, —C(O)R 11 , —CO 2 R 11 and —C(O)NR 12 R 13 .
39. The compound of claim 35 , wherein L is O.
40. The compound of claim 35 , wherein L is S.
41. The compound of claim 35 , wherein each R 9 is hydrogen.
42. The compound of claim 35 , wherein R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, NR 12 R 13 , and (C 3 -C 8 )heterocycloalkyl.
43. The compound of claim 42 , wherein R 7 is selected from the group consisting of
wherein
Q is N or CH;
T is CHR 16 , NR 16 , O, or S(O) 1 ;
R 16 is H or (C 1 -C 8 )alkyl;
each R 23 is a member independently selected from the group consisting of H and (C 1 -C 8 )alkyl;
each R 24 is selected from the group consisting of H, (C 1 -C 8 )alkyl;
and heteroalkyl;
the subscript 1 is an integer of from 0 to 2.
44. The compound of claim 42 , wherein R 7 is selected from the group consisting of cyclopentyl, cyclohexyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, and azepinyl.
45. The compound of claim 35 , wherein R 7 is X 2 —C(O)OR 15 or X 2 —C(O)N(R 15 ) 2 ; and each R 15 is H or (C 1 -C 8 )alkyl.
46. A compound having the formula (IX):
wherein
R 4 is selected from the group consisting of H, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl; (C 1 -C 8 )alkoxy, —CO 2 R 11 , —C(O)NR 12 R 13 , hydroxy(C 1 -C 8 )alkyl and C(O)R 11 ;
R 5 is selected from the group consisting of H, (C 1 -C 8 )alkyl, C(O)R 11 and —CO 2 R 11 ;
L is selected from the group consisting of O, S(O) k , CR a R b and C(O);
each R a or R b is independently selected from the group consisting of hydrogen, cyano, nitro, and (C 1 -C 8 )alkyl;
R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl, aryl, NR 12 R 13 , (C 3 -C 8 )heterocycloalkyl, X 2 —C(O)OR 15 , X 2 —C(O)N(R 15 ) 2 , and —X 2 —NR 12 R 13 ;
each X 2 is (C 1 -C 8 )alkylene;
each R 8 is independently selected from the group consisting of halo, (C 1 -C 8 )alkyl, halo(C 1 -C 8 )alkyl;
each R 9 is a member independently selected from the group consisting of halogen, nitro, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy and NR 12 R 13 ;
each R 11 is independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, aryl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, (C 3 -C 8 ) heterocycloalkyl and aryl(C 1 -C 8 )alkyl;
each R 12 and R 13 are independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 3 -C 8 )cycloalkyl, (C 2 -C 8 )heteroalkyl, (C 1 -C 8 )alkoxy, aryl and aryl(C 1 -C 8 )alkyl;
optionally, R 12 and R 13 are combined with the nitrogen atom to which each is attached to form a 3-, 4-, 5-, 6- or 7-membered ring which can be saturated or unsaturated and contain 0 to 2 additional heteroatoms selected from N, O and S; wherein said ring is optionally substituted with from one to four substituents selected from the group consisting of hydroxy, oxo, and (C 1 -C 8 )alkyl;
each R 15 is selected from the group consisting of H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl and (C 3 -C 8 )cycloalkyl; and
the subscript q is an integer of from 0 to 2; and
the subscript p is an integer of from 0 to 3.
47. The compound of claim 46 , wherein L is S.
48. The compound of claim 46 , wherein each R 9 is hydrogen.
49. The compound of claim 46 , wherein R 7 is selected from the group consisting of (C 1 -C 8 )alkyl, NR 12 R 13 , and (C 3 -C 8 )heterocycloalkyl.
50. The compound of claim 49 , wherein R 7 is selected from the group consisting of
wherein
Q is N or CH;
T is CHR 16 , NR 16 , O or S(O) 1 ;
R 16 is H or (C 1 -C 8 )alkyl;
each R 23 is a member independently selected from the group consisting of H and (C 1 -C 8 )alkyl;
each R 24 is selected from the group consisting of H, (C 1 -C 8 )alkyl and heteroalkyl; and
the subscript 1 is an integer of from 0 to 2.
51. The compound of claim 49 , wherein R 7 is selected from the group consisting of cyclopentyl, cyclohexyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, and azepinyl.
52. The compound of claim 46 , wherein
R 7 is X 2 —C(O)OR 15 or X 2 —C(O)N(R 15 ) 2 ; and
each R 15 is H or (C 1 -C 8 )alkyl.
53. A composition comprising a pharmaceutically acceptable carrier or excipient and a compound of claim 1 .
54. A method for treating a condition or disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , wherein the condition or disorder is selected from the group consisting of obesity, hypercholesterolemia, hyperlipidemia, dyslipidemia, hypertriglyceridemia, hyperglycemia, insulin resistance, hyperinsulinemia, syndrome X, atherosclerosis, rheumatoid arthritis, asthma, septic shock, ileus and migraine.
55. A method in accordance with claim 54 , wherein said subject is a human.
56. A method in accordance with claim 54 , wherein said administering is oral.
57. A method in accordance with claim 54 , wherein said administering is parenteral.
58. A method in accordance with claim 54 , wherein said administering is topical.
59. A method in accordance with claim 54 , wherein said condition or disorder is selected from the group consisting of diabetes, obesity, hypercholesterolemia, hyperlipidemia, dyslipidemia, hypertriglylceridemia, hyperglycemia, insulin resistance, hyperinsulinemia, and syndrome X.
60. A method in accordance with claim 54 , wherein said condition or disorder is rheumatoid arthritis.
61. A method in accordance with claim 54 , wherein said condition or disorder is atherosclerosis.
62. A method in accordance with claim 54 , wherein said condition or disorder is asthma.
63. A method in accordance with claim 54 , wherein said condition or disorder is septic shock.
64. A method in accordance with claim 54 , wherein said condition of disorder is ileus.
65. A method in accordance with claim 54 , wherein condition or disorder is migraine.
66. A method in accordance with claim 54 , wherein said compound is administered in combination with an anti-diabetic agent, an antiinflammatory agent, a cholesterol lowering agent, a chemotherapeutic agent or hormone therapy.