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1. WO2009076631 - COMPOSES DE CARBOXAMIDE, DE SULFONAMIDE ET D'AMINE SERVANT A TRAITER LES TROUBLES METABOLIQUES

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

What is claimed is:

1. A compound having the structural formula



or a pharmaceutically acceptable salt, prodrug, or JV-oxide thereof, wherein
"B" represents -(aryl or heteroaryl)- substituted by w R3 and k R14;
the dotted line denoted by "b" is absent, a single bond or a double bond;
the dotted line denoted by "a" is a bond or absent, provided that if the dotted line denoted by "b" is a double bond, then the dotted line denoted by "a" is absent;
D is a carbon or N when the dotted line denoted by "a" is absent, and a carbon when the dotted line denoted by "a" is a bond;
J is -O-, -N(R38)-, -CH2-, -CH(R26)- or -C(R26)2-;
E is -C(O)-, -S(O)2- or a single bond, provided that when "B" is phenyl, J is -O- and D is a carbon, E is not -C(O)-;
R1 is H, -(Ci-C4 alkyl), -C(O)-(Ci-C4 alkyl) or -C(O)O-(Ci-C4 alkyl);
R2 is -Hca, -Cak-N(R9)-G-R22 or -(C2-C8 alkyl)-N(R9)-R24 in which one or two carbons of the (C2-C8 alkyl) are optionally replaced by -0-, -S- or -N(R9)- and R24 is -R23,
-G-R23, or -C(O)O-(Ci-C6 alkyl), provided that two consecutive carbons of the (C2-C8 alkyl) are not replaced by -0-;
each R3 is substituted on a benzo, pyrido or pyrazino carbon of the ring system denoted by "B" and is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6
alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10,
-(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN;
w is O, 1, 2 or 3;
each R14 is substituted on a non-benzo, non-pyrido, non-pyrazino carbon of the ring
system denoted by "B", and is independently selected from -(Ci-C6 alkyl), -(Ci-C6 halooalkyl), -(C0-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6
alkyl)-Hca, -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0.2R10, -halogen, -NO2 and -CN;

k is 0, 1 or 2;
each R4 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(Co-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN, and two R4 on the same carbon optionally combine to form oxo;
x is 0, 1, 2, 3 or 4;
p is 0, 1, 2, 3 or 4;
q is O, 1, 2, 3 or 4;
the sum of p and q is 1, 2, 3 or 4;
T is -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6
alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10 or


in which
Q is -S(O)2-, L or -(C0-Cs alkyl)-, in which each carbon of the -(C0-Cs alkyl)- is
optionally and independently substituted with one or two R16;
the ring system denoted by "A" is heteroaryl, aryl, cycloalkyl or heterocycloalkyl; each R5 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6
alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0.2R10, -(C0-C6 alkyl)-C(O)R10, -halogen, -NO2 and -CN; and
y is O, 1, 2, 3 or 4;
in which
each L is independently selected from -NR9C(O)O-, -OC(O)NR9-,
-NR9C(O)-NR9-, -NR9C(O)S-, -SC(O)NR9-, -NR9C(O)-, -C(O)-NR9-,
-NR9C(S)O-, -OC(S)NR9-, -NR9C(S)-NR9-, -NR9C(S)S-, -SC(S)NR9-,
-NR9C(S)-, -C(S)NR9-, -SC(O)NR9-, -NR9C(S)-, -S(O)0-2-, -C(O)O, -OC(O)-, -C(S)O-, -OC(S)-, -C(O)S-, -SC(O)-, -C(S)S-, -SC(S)-, -OC(O)O-, -SC(O)O-, -OC(O)S-, -SC(S)O-, -OC(S)S-, -NR9C(NR2)NR9-, -NR9SO2-, -SO2NR9- and -NR9SO2NR9-, each R6, R7, R8 and R10 is independently selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9-(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6 alkyl)-C(O)-(C0-C6 alkyl) and -(C0-C6 alkyl)-S(0)o-2-(Co-C6 alkyl),
each R9 is independently selected from -H, -(C1-C4 alkyl), -C(O)-(Ci-C4 alkyl)
and -C(O)O-(Ci-C4 alkyl),
each G is independently -S(O)2-, L or -(C0-Cs alkyl)-, in which each carbon of the -(C0-C3 alkyl)- is optionally and independently substituted with one or two
R16,
each R16 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6
alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0.2R10, -halogen, -NO2 and -CN, and
optionally two of R16 on the same carbon combine to form oxo,
each R26 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6
alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0.2R10, -halogen, -NO2 and -CN, and
optionally two of R26 on the same carbon combine to form oxo,
each R38 is independently selected from -H, -(CrC4 alkyl), -C(O)-(Ci-C4 alkyl)
and -C(O)O-(Ci-C4 alkyl),
each R22 and R23 is independently Ar or Het,
each Ar is an optionally substituted aryl,
each Het is an optionally substituted heteroaryl,
each Cak is an optionally substituted cycloalkyl,
each Hca is an optionally substituted heterocycloalkyl, and
each alkyl is optionally substituted,
wherein the compound is not
5-methyl-N,2-bis(tetrahydro-2H-pyran-4-yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3- b]indole-8-carboxamide or
5-methyl-2-(tetrahydro-2H-pyran-4-yl)-Λ/-(tetrahydrothiophen-2-yl)-2, 3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide S^S-dioxide.

2. A compound according to claim 1, wherein "B" represents
the dotted line denoted by "b" is a single bond, the dotted line denoted by "a" is a bond, k is 0, J is -N(R38)-and D is a carbon .

3. A compound according to claim 1, wherein "B" represents
the dotted line denoted by "b" is absent, the dotted line denoted by "a" is absent, k is 0, J is -N(R38)- and D is a carbon .

4. A compound according to claim 1, wherein the "B" represents
in which X1 and X2 are independently a carbon or N, and k is 0.

5. A compound according to claim 4, wherein one of X1 and X2 is a carbon and the other is

N.

6. A compound according to claim 1, wherein "B" represents
in which R39 is H, -(Ci-C4 alkyl), -C(O)-(Ci-C4 alkyl) or -C(O)O-(Ci-C4 alkyl).

7. A compound according to claim 6, wherein R14 is substituted on a pyrrolo carbon, and wherein R14 is selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl) (e.g., difluoromethyl, trifiuoromethyl and the like), -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0.2R10, -halogen, -NO2 and -CN, in which each R7, R8 and R10 is independently selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(Co-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6 alkyl)-C(0)-(Co-C6 alkyl), and -(C0-C6 alkyl)-S(O)0.2-(C0-C6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or
heterocycloalkyl-containing group .

8. A compound according to claim 6, wherein no R14 is substituted on the pyrrolo carbon.

9. A compound according to any of claims 1-8, wherein E is -C(O)-.

10. A compound according to any of claims 1-8, wherein T is
( w

11. A compound according to claim 10, wherein each R16 is independently selected from -(Ci-C6 alkyl), -(CrC6 haloalkyl), -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN, and two R16 on the same carbon optionally combine to form an oxo, in which each R7, R8 and R10 is independently selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(0)-(Co-C6 alkyl), and -(C0-C6 alkyl)-S(O)0.2-(C0-C6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group.

12. A compound according to claim 10 or claim 11, wherein Q has at most one R16 or an oxo substituted thereon.

13. A compound according to claim 10, wherein Q is an unsubstituted -(C1-C3 alkyl)-.

14. A compound according to claim 10, wherein Q is -CH2-, a single bond, -C(O)-, -S(O)2-or -CH(CH3)-.

15. A compound according to any of claims 10-14, wherein y is 0.

16. A compound according to any of claims 10-14, wherein y is 1.

17. A compound according to any of claims 10-14, wherein each R5 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0.2R10, -halogen, -NO2 and -CN, in which each R7, R8 and R10 is independently selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6 alkyl)-C(O)-(C0-C6 alkyl) and -(C0-C6 alkyl)-S(O)0.2-(C0-C6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl-or heterocycloalkyl-containing group.

18. A compound according to any of claims 10-17, wherein the ring system denoted by "A" is an aryl or a heteroaryl.

19. A compound according to any of claims 10-17, wherein the ring system denoted by "A" is a phenyl.

20. A compound according to any of claims 10-17, wherein the ring system denoted by "A" is a heteroaryl.

21. A compound according to any of claims 10-17, wherein the ring system denoted by "A" is a pyridyl, a thienyl, or a furanyl.

22. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula


23. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula


24. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula

wherein k is 0, q is 1, 2, 3 or 4, J is -CH2-, -CH(R 2260Λ)- or -C(R > 2Z60Λ)2-.

25. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula



wherein k is 0, q is 1, 2, 3 or 4, J is -CH2-, -CH(R26)- or -C(R26)2-.

26. A compound according to any of claims 1 or 9-25, wherein the sum of p and q is 2 or 3.

27. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula



wherein k is 0 and n is 0, 1, 2 or 3.

28. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula



wherein k is 0 and n is 0, 1, 2 or 3.

29. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula

wherein k is 0, n is 0, 1, 2 or 3, and one of X1 and X2 is N and the other is a carbon .

30. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula



wherein k is 0, n is 0, 1, 2 or 3, and one of X1 and X2 is N and the other is a carbon .

31. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula



wherein n is 0, 1, 2 or 3.

32. A compound according to any of claims 1 or 9-21, wherein the compound has the structural formula



wherein n is 0, 1, 2 or 3..

33. A compound according to any of claims 27-32, wherein n is 1 or 2.

34. A compound according to any of claims 27-32, wherein n is 2.

35. A compound according to any of claims 1-34, wherein R1 is H.

36. A compound according to any of claims 1-35, wherein R2 is Hca.

37. A compound according to claim 36, wherein R2 is an optionally-substituted monocyclic heterocycloalkyl.

38. A compound according to claim 36, wherein R2 is -(optionally-substituted azetidin-3-yl), -(optionally substituted piperidin-4-yl), -(optionally substituted pyrrolidin-3-yl) or
-(optionally- substituted azepan-4-yl) .

39. A compound according to claim 36 wherein R2 is -(optionally substituted piperidin-4-yl).

40. A compound according to claim 36, wherein R2 is -(optionally substituted
pyrrolidin-3-yl).

41. A compound according to any of claims 38-40, wherein R2 is substituted at its 1 -position with -(C0-C3 alkyl)-Ar or -(C0-C3 alkyl)-Het.

42. A compound according to any of claims 38-40, wherein R2 is substituted at its 1-position with -C(O)-O(C0-C6 alkyl), -C(O)-Het, -C(O)-Ar, -S(O)2-Het, -S(O)2-Ar or -S(O)2-O(C0-C6 alkyl).

43. A compound according to any of claims 38-40, wherein R2 is substituted at its 1-position with -C(O)-NR9-Het or -C(O)- NR9-Ar.

44. A compound according to any of claims 1-35 wherein R2 is -Cak-N(R9)-G-R22.

45. A compound according to any of claims 1-35, wherein R2 is -(C2-Cg alkyl)-N(R9)-R24 in which one or two carbons of the (C2-Cg alkyl) are optionally replaced by -O- or -N(R9)- and R24 is -R23, -GR23, or -C(O)O-(Ci-C6 alkyl).

46. A compound according to any of claims 1-45, wherein w is 0.

47. A compound according to any of claims 1-45, wherein w is at least 1 and at least one R3 is selected from the group consisting of halo, cyano, -(Ci-C4 fluoroalkyl), -0-(Ci-C4 fluoroalkyl), -C(O)-(C0-C4 alkyl), -C(O)O-(C0-C4 alkyl), -C(O)N(C0-C4 alkyl)(C0-C4 alkyl), -S(O)2O-(C0-C4 alkyl), NO2 and -C(O)-Hca in which the Hca includes a nitrogen atom to which the -C(O)- is bound, in which no alkyl, fluoroalkyl or heterocycloalkyl is substituted with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.

48. A compound according to any of claims 1-45, wherein each R3 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN, in which each R7, R8 and R10 is independently selected from H, -(C1-C6 alkyl), -(C1-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-0-(Co-C6 alkyl), -(C0-C6 alkyl)-C(O)-(C0-C6 alkyl), and -(C0-C6 alkyl)-S(O)0_2-(C0-C6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl-or heterocycloalkyl-containing group.

49. A compound according to any of claims 1-48 wherein x is 0.

50. A compound according to any of claims 1-48, wherein each R4 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN, in which each R7, R8 and R10 is independently selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-0-(Co-C6 alkyl), -(C0-C6 alkyl)-C(O)-(C0-C6 alkyl) and -(C0-C6 alkyl)-S(O)0.2-(C0-C6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl-or heterocycloalkyl-containing group.

51. A compound according to any of claims 1-35 or 46-50, having the structural formula
17



in which
Q and G are each independently a bond, -CH2-, -C(H)(R16)-, -C(R16)2-, L or -S(O)2-; v is 0, 1, 2, 3 or 4;
each R15 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6
alkyl)-Ar, -(C0-C6 alkyl)-Het, -(C0-C6 alkyl)-Cak, -(C0-C6 alkyl)-Hca, -(C0-C6
alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN, and two R15 on the same
carbon optionally combine to form oxo;
R17 is Het or Ar.

52. A compound according to claim 51, wherein each R15 is independently selected from -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-R7, -(C0-C6 alkyl)-NR8R9, -(C0-C6 alkyl)-OR10, -(C0-C6 alkyl)-C(O)R10, -(C0-C6 alkyl)-S(O)0_2R10, -halogen, -NO2 and -CN and two R15 on the same carbon optionally combine to form oxo, in which each R7, R8 and R10 is independently selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(O)-(C0-C6 alkyl) and -(C0-C6 alkyl)-S(O)0_2-(C0-C6 alkyl), and in which no alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group.

53. A compound according to claim 51 or claim 52, having the structural formula


in which R27 is selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(O)-(C0-C6 alkyl) -(C0-C6 alkyl)-S(O)0_2-(C0-C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group, and R29 is -H, -(Ci-C4 alkyl), -C(O)-(Ci-C4 alkyl) or -CO-O-(Ci-C4 alkyl) in which no (Ci-C4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group, or R27 and R29 together with the nitrogen to which they are bound form Hca.

54. A compound according to claim 51 or claim 52, having the structural formula


in which R27 is selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6 alkyl)-C(O)-(C0-C6 alkyl) -(C0-C6 alkyl)-S(0)o-2-(C0-C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group, and R29 is -H, -(Ci-C4 alkyl), -CO-O-(Ci-C4 alkyl) or -CO-O-(Ci-C4 alkyl) in which no (Ci-C4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group, or R27 and R29 together with the nitrogen to which they are bound form Hca.

55. A compound according to claim 51 or claim 52, having the structural formula


in which R27 is selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(O)-(C0-C6 alkyl) -(C0-C6 alkyl)-S(O)0_2-(C0-C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group, and R29 is -H, -(Ci-C4 alkyl), -CO-O-(Ci-C4 alkyl) or -CO-O-(Ci-C4 alkyl) in which no (Ci-C4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group, or R27 and R29 together with the nitrogen to which they are bound form Hca.

56. A compound according to claim 51 or claim 52, having the structural formula



in which R27 is selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(O)-(C0-C6 alkyl) -(C0-C6 alkyl)-S(O)0_2-(C0-C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl- containing group, and R29 is -H, -(Ci-C4 alkyl), -CO-O-(Ci-C4 alkyl) or -CO-O-(Ci-C4 alkyl) in which no (Ci-C4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group, or R27 and R29 together with the nitrogen to which they are bound form Hca.

57. A compound according to claim 51 or claim 52, having the structural formula


58. A compound according to claim 51 or claim 52, having the structural formula



in which R , 25 is selected from halo, cyano, -(Ci-C4 haloalkyl), -0-(Ci-C4 haloalkyl), -(Ci-C4 alkyl), -0-(Ci-C4 alkyl), -C(O)-(C0-C4 alkyl), -C(O)O-(C0-C4 alkyl), -C(O)N(C0-C4 alkyl)(C0-C4 alkyl), NO2 and -C(O)-Hca in which the Hca contains a ring nitrogen atom through which it is bound to the -C(O)-, in which no alkyl or haloalkyl is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group.

59. A compound according to claim 51 or claim 52, having the structural formula



in which Q is -C(O)-, -S(O)2- or -C(O)-NH-.

60. A compound according to claim 51 or claim 52, having the structural formula 17

in which R , 2z7/ is selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(O)-(C0-C6 alkyl) -(C0-C6 alkyl)-S(O)0_2-(C0-C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group, and R29 is -H, -(Ci-C4 alkyl), -CO-O-(Ci-C4 alkyl) or -CO-O-(Ci-C4 alkyl) in which no (Ci-C4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group, or R27 and R29 together with the nitrogen to which they are bound form Hca.

61. A compound according claim 51 or claim 52, having the structural formula


in which R27 is selected from H, -(Ci-C6 alkyl), -(Ci-C6 haloalkyl), -(C0-C6 alkyl)-L-(C0-C6 alkyl), -(C0-C6 alkyl)-NR9(C0-C6 alkyl), -(C0-C6 alkyl)-O-(C0-C6 alkyl), -(C0-C6
alkyl)-C(O)-(C0-C6 alkyl) -(C0-C6 alkyl)-S(O)0.2-(C0-C6 alkyl), in which no heterocycloalkyl, alkyl or haloalkyl is substituted with an aryl-, heteroaryl-, cycloalkyl- or heterocycloalkyl-containing group, and R29 is -H, -(Ci-C4 alkyl), -CO-O-(Ci-C4 alkyl) or -CO-O-(Ci-C4 alkyl) in which no (Ci-C4 alkyl) is substituted by an aryl, heteroaryl, cycloalkyl or heterocycloalkyl-containing group, or R27 and R29 together with the nitrogen to which they are bound form Hca.

62. A compound according to any of claims 51-61, having the structural formula

63. A compound according to any of claims 51-61, having the structural formula



64. A compound according to any of claims 51-61, having the structural formula



wherein J is -CH2-,

65. A compound according to any of claims 51-61, having the structural formula



wherein J is -CH2-,

66. A compound according to any of claims 51-61, having the structural formula



67. A compound according to any of claims 51-61, having the structural formula



68. A compound according to any of claims 51-61, having the structural formula



wherein one of X1 and X2 is N, and the other is a carbon .
69. A compound according to any of claims 51-61, having the structural formula



wherein one of X1 and X2 is N, and the other is a carbon .
70. A compound according to any of claims 51-61, having the structural formula

71. A compound according to any of claims 51-61, having the structural formula


72. A compound according to any of claims 51-71, wherein the
moiety
-R ,17

has the structure
, in which G is -CH2-, -CH(CH3)-, -C(O)-, -S(O)2- or -C(O)-NH-.

73. A compound according to any of claims 51-59 and 62-71, wherein the



in which G is -CH2-, -C(O)-, -S(O)2- or -C(O)-NH-.

74. A compound according to any of claims 51-59 and 62-71, wherein the


in which G is -CH2-, -C(O)-,

-S(O)2- or -C(O)-NH-.

75. A compound according to claim 1, wherein the compound is
benzyl 8-(l-(4-cyanobenzyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-lH-pyrido[4,3- b]indole-2(5H)-carboxylate;
benzyl 8-(l-(4-benzyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-lH-pyrido[4,3-b]indole- 2(5H)-carboxylate;
benzyl 8-(l-(tert-butoxycarbonyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-lH- pyrido[4,3-b]indole-2(5H)-carboxylate;
2-benzyl-Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3- b]indole-8-carboxamide;
2-benzyl-Λ/-(l-(4-trifluoromethylbenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
tert-butyl 4-(2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole- 8-carboxamido)piperidine- 1 -carboxylate;
2-benzyl-Λ/-(l-(pyridin-4-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3- b]indole-8-carboxamide;
2-(4-fluorobenzyl)-Λ/-(l-(pyridin-3-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-2-(4-fluorobenzyl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-trifluoromethylbenzyl)piperidin-4-yl)-2-(4-fluorobenzyl)-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-trifluoromethylbenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2, 3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;

N-(I -phenethylpiperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro- IH- pyrido[4,3-b]indole-8-carboxamide;
N-(l-(4-fluorophenyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-5-methyl-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
N-(I -(4-trifluoromethylbenzyl)piperidin-4-yl)-5 -methyl-2-(4- (trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8- carboxamide;
5 -methy WV-( 1 -(pyridin-3 -ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)- 2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
N-(I -benzylpiperidin-4-yl)-2-(4-(trifluoromethyl)phenylsulfonyl)-2, 3,4, 5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
5 -acetyi-N-( 1 -(pyridin-3 -ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)- 2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(pyridin-3-ylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
2-(4-(trifluoromethyl)benzyl)-Λ/-(l-(4-(trifluoromethyl)phenylsulfonyl)piperidin-4- yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)phenylsulfonyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
N-(I -(4-cyanobenzyl)piperidin-4-yl)-2-(4-cyanophenylsulfonyl)-2, 3,4, 5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-2-(pyridin-3-ylsulfonyl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-cyanophenylcarbamoyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-fluorophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(3-cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;

2-(4-(trifluoromethyl)benzyl)-Λ/-(l-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4- yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(3-fluorophenylcarbamoyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-chlorophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
2-(4-(trifluoromethyl)benzyl)-Λ/-(l-(4-(trifluoromethyl)phenylcarbamoyl)piperidin-4- yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
N-(I -(4-cyanobenzyl)piperidin-4-yl)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro- IH- pyrido[4,3-b]indole-8-carboxamide;
2-(4-fluorophenyl)-Λ/-(l-(4-fluorophenylsulfonyl)piperidin-4-yl)-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
2-(4-fluorophenyl)-Λ/-(l-(pyridin-3-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
2-(4-fluorophenyl)-Λ/-(l-(4-(trifluoromethyl)benzyl)piperidin-4-yl)-2, 3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
tert-butyl 4-(2-(4-fluorophenyl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8- carboxamido)piperidine- 1 -carboxylate;
Λ/-(l-(4-fluorobenzoyl)piperidin-4-yl)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
2-(4-fluorophenyl)-Λ/-(l-nicotinoylpiperidin-4-yl)-2,3,4,5-tetrahydro-lH-pyrido[4,3- b]indole-8-carboxamide;
2-(4-fluorophenyl)-Λ/-(l-(4-(trifluoromethyl)benzoyl)piperidin-4-yl)-2, 3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
N-(I -nicotinoylpiperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2, 3,4, 5-tetrahydro- IH- pyrido[4,3-b]indole-8-carboxamide;
tert-butyl 4-(2-(4-carbamoylbenzyl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8- carboxamido)piperidine- 1 -carboxylate;
2-(4-carbamoylbenzyl)-Λ/-(l-(4-cyanobenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;
2-(4-carbamoylbenzyl)-Λ/-(l-(pyridin-4-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
2-(4-carbamoylbenzyl)-iV-(l -isonicotinoylpiperidin-4-yl)-2, 3,4, 5-tetrahydro- IH- pyrido[4,3-b]indole-8-carboxamide;

2-(4-carbamoylbenzyl)-Λ/-(l-(4-(trifluoromethyl)benzyl)piperidin-4-yl)-2, 3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
2-(4-carbamoylbenzyl)-Λ/-(l-(4-fluorobenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-lH- pyrido[4,3-b]indole-8-carboxamide;;
2-(4-carbamoylbenzyl)-Λ/-(l-(4-carbamoylbenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide
Λ/-(l-(pyridin-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-isonicotinoylpiperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro- lH-pyrido[4,3-b]indole-8-carboxamide;
Λ/-(l-(4-carbamoylbenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
N-( 1 -(( 1 -methyl- lH-imidazol-4-yl)methyl)piperidin-4-yl)-2-(4- (trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-lH-pyrido[4,3-b]indole-8- carboxamide;
N-(I -(oxazol-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3, 4,5- tetrahydro-lH-pyrido[4,3-b]indole-8-carboxamide;
4-((4-benzylpiperazin- 1 -yl)methyl)-JV-(l -benzylpiperidin-4-yl)benzamide
N-(I -benzylpiperidin-4-yl)-4-((4-(cyclohexylmethyl)piperazin- 1 - yl)methyl)benzamide;
N-(I -benzylpiperidin-4-yl)-4-((4-(5 -(trifluoromethyl)pyridin-2-yl)piperazin- 1 - yl)methyl)benzamide;
N-(I -benzylpiperidin-4-yl)-4-((4-(pyridin-2-yl)piperazin- 1 -yl)methyl)benzamide 4-((4-benzylpiperazin- 1 -yl)methyl)-Λ/-(l -(pyridin-4-ylmethyl)piperidin-4- yl)benzamide;
4-((4-benzylpiperazin- 1 -yl)methyl)-Λ/-(l -(pyridin-3-ylmethyl)piperidin-4- yl)benzamide;
4-((4-benzylpiperazin- 1 -yl)methyl)-N-( 1 -(4-cyanobenzyl)piperidin-4-yl)benzamide 4-((4-benzylpiperazin- 1 -yl)methyl)-Λ/-(l -(4-trifluoromethylbenzyl)piperidin-4- yl)benzamide;
N-( 1 -benzylpiperidin-4-yl)-6-( 1 -(4-(trifluoromethyl)benzyl)piperidin-4-yloxy)-2- naphthamide;
N-(I -benzylpiperidin-4-yl)-6-( 1 -(4-cyanobenzyl)piperidin-4-yloxy)-2-naphthamide N-(I -benzylpiperidin-4-yl)-6-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2- naphthamide;
tert-butyl 4-(7-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2- naphthamido)piperidine- 1 -carboxylate;
tert-butyl 4-(6-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)quinoline-3 - carboxamido)piperidine- 1 -carboxylate;
jV-(piperidin-4-yl)-6-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)quinoline-3 - carboxamide;
N-(I -(4-cyanobenzyl)piperidin-4-yl)-6-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4- yloxy)quinoline-3 -carboxamide;
N-( 1 -(4-(trifluoromethyl)benzyl)piperidin-4-yl)-6-( 1 -(4- (trifluoromethyl)phenyl)piperidin-4-yloxy)quinoline-3-carboxamide;
N-(I -benzylpiperidin-4-yl)-6-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4- yloxy)quinoline-3 -carboxamide; or
N-( 1 -benzylpiperidin-4-yl)-5-( 1 -(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)- IH- indole-2-carboxamide.

76. A pharmaceutical composition comprising:
at least one pharmaceutically acceptable carrier, diluent or excipient; and
a compound according to any of claims 1-75 or a pharmaceutically acceptable salt, prodrug or N-oxide thereof.

77. A method for activating the AMPK pathway in a cell, the method comprising
contacting the cell with an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

78. A method for increasing fatty acid oxidation in a cell, the method comprising
contacting the cell with an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

79. A method for decreasing glycogen concentration in a cell, the method comprising
contacting the cell with an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

80. A method for increasing glucose uptake in a cell, the method comprising
contacting the cell with an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

81. A method for reducing triglyceride levels in a subject, the method comprising
administering to the subject an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

82. A method for treating type II diabetes in a subject, the method comprising
administering to the subject an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

83. A method for treating or preventing atherosclerosis or cardiovascular disease in a subject, the method comprising
administering to the subject an effective amount of a compound according to any of
claims 1-75, or a pharmaceutically acceptable salt, prodrug or JV-oxide thereof, or an effective amount of a composition according to claim 76.

84. A labeled conjugate having the structural formula



in which the "LINK" moiety is a linker and is optional, and the "LABEL" moiety is a

labeling agent, and the
moiety is as described in any of claims 1-75.