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1. CA2707047 - 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 ]
THE EMBODIMENTS OF THE INVENTION FOR WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A compound having the structural formula or a pharmaceutically acceptable salt or N-oxide thereof, wherein the group is or in which R38 is H, -(C1-C4 alkyl), -C(O)-(C1-C4 alkyl) or -C(O)O-(C1-C4 alkyl); which one of X1 and X2 is N and the other is CH or C substituted by one of the R3; or
or in which R14 is halo, cyano, -(C1-C4 alkyl) or -(C1-C4 haloalkyl), and R39 is H, -(C1-C4 alkyl), -C(O)-(C1-C4 alkyl) or -C(O)O-(C1-C4 alkyl); and wherein E is -C(O)-, -S(O)2- or a single bond; R1 is H, -(C1-C4 alkyl), -C(O)-(C1-C4 alkyl) or -C(O)O-(C1-C4 alkyl); each R15 is independently selected from -(C1-C3 alkyl), -(C1-C3 haloalkyl), (Co-C3 alkyl)-L-R7, -(C0-C3 alkyl)-NR8R9, -(C0-C3 alkyl)-OR10, -(C0-C3 alkyl)C(O)R10, -(C0-C3 alkyl)-S(O)0-2R10, -halogen, -NO2 and -CN, and two R15 on the same carbon optionally combine to form oxo; v is 0, 1 or 2; G is -CH2-, -CH(CH3)-, -C(O)-, -S(O)2- or -C(O)-NH-; R17 is aryl or heteroaryl, each optionally substitued by 1, 2 or 3 substituents independently selected from -(C1-C3 alkyl), -(C1-C3 haloalkyl), -(C0-C3 alkyl)-L-R7, -(CO-C3
alkyl)-NR8R9, -(C0-C3 alkyl)-OR10, -(C0-C3 alkyl)-C(O)R10, -(C0-C3 alkyl)S(O)0-2R10, -halogen, -NO2 and -CN; each R3 is substituted on a benzo, pyrido or pyrazino carbon of the ring system denoted by "B" and is independently selected from -(C1-C3 alkyl), -(C1-C3 haloalkyl), (CO-C3 -(C0-C3 alkyl)-NR8R9, -(C0-C3 alkyl)-OR10, -(C0-C3 alkyl)-C(O)R10, -(C0-C3 alkyl)-S(O)0-2R10, -halogen, -NO2 and -CN; w is 0, 1 or 2; each R4 is independently selected from -(C1-C3 alkyl), -(C1-C3 haloalkyl), (C0-C3 alkyl)-L-R7, -(C0-C3 alkyl)-NR8R9, -(C0-C3 alkyl)-OR10, -(C0-C3 alkyl)C(O)R10, -(C0-C3 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 or 2; Q is a single bond, -CH2-, -C(O)- or -S(O)2-; the ring system denoted by "A" is phenyl or monocyclic heteroaryl;
each R5 is independently selected from -(C1-C3 alkyl), -(C1-C3 haloalkyl), (C0-C3 alkyl)-L-R7, -(C0-C3 alkyl)-NR8R9, -(C0-C3 alkyl)-OR10, -(C0-C3 alkyl)C(O)R10, -(C0-C3 alkyl)-S(O)0-2R10, -halogen, -NO2 and -CN; and y is 0, 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 R7, R8 and R10 is independently selected from H, -(C1-C2 alkyl), -(C1-C2 haloalkyl), -(C0-C2 alkyl)-L-(C0-C2 alkyl), -(C0-C2 alkyl)-NR9(C0-C2 alkyl), -(C0-C2 alkyl)-O-(C0-C2 alkyl), -(C0-C2 alkyl)-C(O)-(C0-C2 alkyl) and -(C0-C2 alkyl)-S(O)0-2-(C0-C2 alkyl), and each R9 is independently selected from -H, -(C1-C4 alkyl), -C(O)-(C1-C4 alkyl)
and -C(O)0-(C1-C4 alkyl). 2. A compound according to claim 1, wherein the group is or
3. A compound according to claim 2, wherein R38 is H.
4. A compound according to claim 1, wherein the group is or
5. A compound according to claim 1, wherein the group is or
6. A compound according to claim 1, wherein the group is or
7. A compound according to claim 1, wherein the < > group is or
8. A compound according to claim 7, wherein R14 is present.
9. A compound according to claim 7, wherein R14 is absent.
10. A compound according to any one of claims 7-9, wherein R39 is H.
11. A compound according to any one of claims 1-10, wherein E is -C(O)-.
12. A compound according to any one of claims 1-11, wherein Q is a single bond.
13. A compound according to any one of claims 1-11, wherein Q is -CH2-.
14. A compound according to any one of claims 1-11, wherein Q is -C(O)- or S(O)2-.
15. A compound according to any one of claims 1-14, wherein y is 0.
16. A compound according to any one of claims 1-14, wherein y is 1.
17. A compound according to any one of claims 1-16, wherein the ring system denoted by "A" is a phenyl.
18. A compound according to any one of claims 1-16, wherein the ring system denoted by "A" is a monocyclic heteroaryl.
19. A compound according to any one of claims 1-16, wherein the ring system denoted by "A" is a pyridyl, a thienyl, or a furanyl.
20. A compound according to any one of claims 1-19, wherein R1 is H.
21. A compound according to any one of claims 1-20, wherein the moiety is
22. A compound according to any one of claims 1-21, wherein G is -CH2-.
23. A compound according to any one of claims 1-21, wherein G is -C(O)- or S(O)2-.
24. A compound according to any one of claims 1-23, wherein R17 is phenyl optionally substituted with 0, 1, 2 or 3 substituents independently selected from -(C1-C3 alkyl), -(C1-C3 haloalkyl), -(C0-C3 alkyl)-L-R7, -(C0-C3 alkyl)-NR8R9, -(C0-C3 alkyl)-OR10, (C0-C3 alkyl)-C(O)R10, -(C0-C3 alkyl)-S(O)0-2R10, -halogen, -NO2 and -CN.
25. A compound according to any one of claims 1-24, wherein w is 0.
26. A compound according to any one of claims 1-25, wherein x is 0.
27. A compound according to any one of claims 1-14, 16-23, 25 and 26, having the structural formula
28. A compound according to any one of claims 1-14 and 15-26, having the structural formula
in which R25 is selected from halo, cyano, -(C1-C3 haloalkyl), -O-(C1-C2 haloalkyl), -(C1-C3 alkyl), -O-(C1-C2 alkyl), -C(O)-(C0-C2 alkyl), -C(O)O-(C0-C2 alkyl), -C(O)N(C0-
alkyl)(C0-C4 alkyl) and NO2.
29. A compound according to any one of claims 1-14, 16, 17, 20-23, 25 and 26, having the structural formula
30. A compound according to any one of claims 1-3 and 11-29, having the structural formula
31. A compound according to any one of claims 1-3 and 11-29, having the structural formula
32. A compound according to any one of claims 1, 4 and 11-29, having the structural formula
33. A compound according to any one of claims 1, 4 and 11-29, having the structural formula
34. A compound according to any one of claims 1, 5 and 11-29, having the structural formula
35. A compound according to any one of claims 1, 5 and 11-29, having the structural formula
36. A compound according to any one of claims 1, 6 and 11-29, having the structural formula
37. A compound according to any one of claims 1, 6 and 11-29, having the structural formula
38. A compound according to any one of claims 1, 6 and 11-29, having the structural formula
39. A compound according to any one of claims 1 and 7-29, having the structural formula
40. A compound according to any one of claims 1-39, wherein the moiety has the structure
41. A compound, which is benzyl 8-(1-(4-cyanobenzyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-1H-pyrido[4,3b]indole-2(5H)-carboxylate; benzyl 8-(1-(4-benzyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-1H-pyrido[4,3b]indole2(5H)-carboxylate; benzyl 8-(1-(tert-butoxycarbonyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-1 Hpyrido[4 ,3-b] indole-2(5H)-carboxylate; 2-benzyl-N-(1-(4-cyanobenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3b]indole-8-carboxamide; 2-benzyl-N-(1-(4-tnfluoromethylbenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-1Hpyrido[4,3-b]indole-8-carboxamide; tert-butyl 4-(2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3b]indole8-carboxamido)piperidine-1-carboxylate; 2-benzyl-N-(1-(pyridin-4-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro-1Hpyrido14,313]indole-8-carboxamide; 2-(4-fluorobenzyl)-N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro-
pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-2-(4-fluorobenzyl)-2,3,4,5-tetrahydro-1Hpyrido[4,3-b]indole-8-carboxamide; N-(1-(4-trifluoromethylbenzyl)piperidin-4-yl)-2-(4-fluorobenzyl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-
tetrahydro-IH-pyrido[4,3-b]indole-8-carboxamide;
N-(1-(4-cyanobenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-trifluoromethylbenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b] indole-8-carboxamide; N-(1-phenethylpiperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-
pyrido[4,3-b] indole-8-carboxamide; N-(1-(4-fluorophenyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-5-methyl-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-trifluoromethylbenzyl)piperidin-4-yl)-5-methyl-2-(4(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8carboxamide; 5-methyl-N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4(trifluoromethyl)benzyl)2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-benzylpipendin-4-yl)-2-(4-(trifluoromethyl)phenylsulfonyl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; 5-acetyl-N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4(trifluoromethyl)benzyl)2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(pyridin-3-ylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; 2-(4-(tnfluoromethyl)benzyl)-N-(1-(4-(trifluoromethyl)phenylsulfonyl)piperidin-
yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)phenylsulfonyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-2-(4-cyanophenylsulfonyl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-2-(pyridin-3-ylsulfonyl)-2,3,4,5tetrahydro-1Hpyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanophenylcarbamoyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide;
N-(1-(4-fluorophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(3-cyanophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; 2-(4-(trifluoromethyl)benzyl)-N-(1-(3(trifluoromethyl)phenylsulfonyl)piperidin-4yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(3-fluorophenylcarbamoyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-chlorophenylsulfonyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; 2-(4-(trifluoromethyl)benzyl)-N-(1-(4(trifluoromethyl)phenylcarbamoyl)piperidin-4yl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1Hpyrido[4,3-b]indole-8-carboxamide; 2-(4-fluorophenyl)-N-(1-(4-fluorophenylsulfonyl)piperidin-4-yl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; 2-(4-fluorophenyl)-N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2,3,4,5-tetrahydro-
pyrido[4,3-b]indole-8-carboxamide; 2-(4-fluorophenyl)-N-(1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)-2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; tert-butyl 4-(2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8carboxamido)piperidine-1-carboxylate; N-(1-(4-fluorobenzoyl)piperidin-4-yl)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-
pyrido[4,3-b]indole-8-carboxamide; 2-(4-fluorophenyl)-N-(1-nicotinoylpiperidin-4-yl)-2,3,4,5-tetrahydro-1Hpyrido[4,3b]indole-8-carboxamide; 2-(4-fluorophenyl)-N-(1-(4-(trifluoromethyl)benzoyl)piperidin-4-yl)-2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-nicotinoylpiperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5tetrahydro-1Hpyrido[4,3-b]indole-8-carboxamide; tert-butyl 4-(2-(4-carbamoylbenzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-
carboxamido)piperidine-1-carboxylate; 2-(4-carbamoylbenzyl)-N-(1-(4-cyanobenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-
pyrido[4,3-b]indole-8-carboxamide;
2-(4-carbamoylbenzyl)-N-(1-(pyridin-4-ylmethyl)piperidin-4-yl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; 2-(4-carbamoylbenzyl)-N-(1-isonicotinoylpiperidin-4-yl)-2,3,4,5-tetrahydro-1Hpyrido[4,3-b]indole-8-carboxamide; 2-(4-carbamoylbenzyl)-N-(1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)-2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; 2-(4-carbamoylbenzyl)-N-(1-(4-fluorobenzyl)piperidin-4-yl)-2,3,4,5-tetrahydro-
pyrido [4,3-b]indole-8-carboxamide; 2-(4-carbamoylbenzyl)-N-(1-(4-carbamoylbenzyl)piperidin-4-yl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(pyridin-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-
tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-isonicotinoylpiperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5tetrahydro1H-pyrido[4,3-b]indole-8-carboxamide; N-(1-(4-carbamoylbenzyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5tetrahydro-1H-pyrido[4,3-b] indole-8-carboxamide; N-(1-((1-methyl-1H-imidazol-4-yl)methyl)piperidin-4-yl)-2-(4(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8carboxamide; N-(1-(oxazol-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide; 4-((4-benzylpiperazin-1-yl)methyl)-N-(1-benzylpiperidin-4-yl)benzamide; N-(1-benzylpiperidin-4-yl)-4-((4-(cyclohexylmethyl)piperazin-1- yl)methyl)benzamide; N-(1-benzylpiperidin-4-yl)-4-((4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-
yl)methyl)benzamide; N-(1-benzylpiperidin-4-yl)-4-((4-(pyridin-2-yl)piperazin-1yl)methyl)benzamide; 4-((4-benzylpiperazin-1-yl)methyl)-N-(1-(pyridin-4-ylmethyl)piperidin-4yl)benzamide; 4-((4-benzylpiperazin-1-yl)methyl)-N-(1-(pyridin-3-ylmethyl)piperidin-4yl)benzamide; 4-((4-benzylpiperazin-1-yl)methyl)-N-(1-(4-cyanobenzyl)piperidin-4yl)benzamide; 4-((4-benzylpiperazin-1-yl)methyl)-N-(1-(4-trifluoromethylbenzyl)piperidin-4yl)benzamide;
N41-benzylpiperidin-4-yl)-6-(1-(4-(trifluoromethyl)benzyl)piperidin-4-yloxy)-2-
naphthamide; N-(1-benzylpiperidin-4-yl)-6-(1-(4-cyanobenzyl)piperidin-4-yloxy)-2naphthamide; N-(1-benzylpiperidin-4-yl)-6-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-
naphthamide; tert-butyl 4-(7-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2naphthamido)piperidine-1-carboxylate; tert-butyl 4-(6-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)quinoline-3carboxamido)piperidine-1-carboxylate; N4piperidin-4-yl)-6-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)quinoline-
carboxamide; N-(1-(4-cyanobenzyl)piperidin-4-yl)-6-(1-(4-(trifluoromethyl)phenyl)piperidin-
yloxy)quinoline-3-carboxamide; N-(1-(4-(trifluoromethyl)benzyl)piperidin-4-yl)-6-(1-(4(trifluoromethyl)phenyl)piperidin-4-yloxy)quinoline-3-carboxamide; N-(1-benzylpiperidin-4-yl)-6-(1-(4-(trifluoromethyl)phenyl)piperidin-4yloxy)quinoline-3-carboxamide; or N-(1-benzylpiperidin-4-yl)-5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-
indole-2-carboxamide.
42. A pharmaceutical composition comprising: at least one pharmaceutically acceptable carrier, diluent or excipient; and a compound according to any one of claims 1-41 or a pharmaceutically acceptable salt or N-oxide thereof.
43. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to activate the AMPK pathway in a cell.
44. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to increase fatty acid oxidation in a cell.
45. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to decrease glycogen concentration in a cell.
46. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to increase glucose uptake in a cell.
47. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to reduce triglyceride levels in a subject.
48. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to treat type II diabetes in a subject.
49. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, or an effective amount of
composition as defined in claim 42, to treat or preventing atherosclerosis or cardiovascular disease in a subject.
50. Use of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to activate the AMPK pathway in a cell.
51. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to increase fatty acid oxidation in a cell.
52. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to decrease glycogen concentration in a cell.
53. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to increase glucose uptake in a cell.
54. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to reduce triglyceride levels in a subject.
55. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to treat type II diabetes in a subject.
56. Use of an effective amount of a compound as defined in any one of claims 1 to 41 or a pharmaceutically acceptable salt or N-oxide thereof, in the manufacture of a medicament to treat or preventing atherosclerosis or cardiovascular disease in
subject.