Certains contenus de cette application ne sont pas disponibles pour le moment.
Si cette situation persiste, veuillez nous contacter àObservations et contact
1. (WO2019005977) AGENTS TRIOXOLANE
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

WHAT IS CLAIMED IS:

A compound having the formula:


(I), wherein

W1 and W2 are independently =N-, =C(R2)-, or =CH-;

L1 is a bond, - 0-, - H-, -OC(O)-, -C(0)0-, -NHC(O)-, -C(0)NH-, -OC(0)0-, -OC(0) H-, - HC(0)0-, -NH C(0) H-, or -S-;

L2 is a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;

R1 is hydrogen, halogen, -CXS, -CHX^, -CH2X1, -OCX^, -OCH2X1, -OCHX1!, -CN, -SOniR1D, -SOvi R1AR1B, - HC(0) R1AR1B, -N(0)mi, - R1AR1B, -C( 0)R1C, -C(0)-ORlc, -C(0) R1AR1B, -OR1D, - R1AS02R1D, - R1AC(0)R1C, - R1AC(0)ORlc, -N R1AORlc, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R2 is independently

halogen, -CX23, -CHX22, -CH2X2, -OCX23, -OCH2X2, -OCHX22, -CN, -OH, -NH2, -COOH, -CO NH2, -NO2, -SH, -S03H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC=(0)NHNH2,

-NHC=(0)NH2, -NHSO2H, -NHC=(0)H, -NHC(0)-OH, -NHOH, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

z2 is an integer from 0 to 4;

each R1A, R1B, R1C, and R1D is independently

hydrogen, -CX3, -COOH, -CONH2, -CHX2, -CH2X, substituted or unsubstituted alkyl,

substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;

each X, X1, and X2 is independently -F, -CI, -Br, or -I;

nl is independently an integer from 0 to 4;

ml and vl are independently 1 or 2.

The compound of claim 1, having the formula:


3. The compound ofclaim 1, wherein W is =N-

4. The compound of claim 1, wherein W is =CH

5. The compound of claim 1, wherein W is =N-

6. The compound of claim 1, wherein W is =CH

7. The compound of claim 1, wherein R2 is independently unsubstituted Ci- C3 alkyl.

8. The compound ofclaim 1, wherein z2 is 0.

9. The compound of claim 1, wherein L1 is -O-

The compound of claim 1, wherein L is -OC(O)-

1 1. The compound of claim 1, wherein L is -OC(0)NH-

The compound of claim 1, wherein L is -OC(0)0

The compound of claim 1, wherein L is a bond

14. The compound of claim 1, wherein L2 is a substituted or unsubstituted Ci-C4 alkylene.

15. The compound of claim 1, wherein L2 is an unsubstituted C1-C4 alkylene.

16. The compound of claim 1, wherein L2 is a substituted or unsubstituted C4-C6 cycloalkylene.

17. The compound of claim 1, wherein L2 is a substituted or unsubstituted 5 to 7 membered heterocycloalkylene.

18. The compound of claim 1, wherein L2 is a bond.

19. The compound of claim 1, wherein R1 is - R1AR1B, -C(0) R1AR1B, R20-substituted or unsubstituted Ci-C6 alkyl, R20-substituted or unsubstituted 2 to 6 membered heteroalkyl, R20-substituted or unsubstituted C5-C7 cycloalkyl, R20-substituted or unsubstituted phenyl, or R20-substituted or unsubstituted 5 to 7 membered heterocycloalkyl;

R20 is independently oxo,

halogen, -CF3, -CHF2, -CH2F, -OCF3, -OCH2F, -OCHF2, -CN, -OH, - H2, -COOH, -CO H2, -N 02, -SH, -S(0)2CH3, unsubstituted Ci-C6 alkyl, unsubstituted 2 to 6 membered heteroalkyl, unsubstituted C3-C6 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl; and

each R1A and R1B is independently hydrogen, substituted or unsubstituted Ci-C6 alkyl, substituted or unsubstituted 2 to 6 membered heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl; R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 5 to 6 membered heterocycloalkyl.

20. The compound of claim 1, wherein R1 is - R1AR1B, -C(0) R1AR1B, or R20-substituted or unsubstituted 6 to 7 membered heterocycloalkyl;

R20 is independently oxo, -OH, -S(0)2CH3; and

each R1A and R1B is independently hydrogen, OH- substituted Ci-C4 alkyl, H2-substituted Ci-C4 alkyl, or unsubstituted 5 to 6 membered heterocycloalkyl.

21. The compound of claim 1, wherein R1 is -OR1D and R1D is hydrogen or unsubstituted Ci-C3 alkyl.






(II), wherein W1 and W2 are independently =N-, =C(R2)-, or =CH-;

L1 is a bond, -0-, - H-, -OC(O)-, -C(0)0-, -NHC(O)-, -C(0)NH-, -OC(0)0-, -OC(0) H-, - HC(0)0-, - H C(0) H-, -S-;

L2 is a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroaryl ene;

R1 is hydrogen, halogen, -CXS, -CHX^, -CH2X1, -OCX^, -OCH2X1, -OCHX1!, -CN, -SOniR1D, -SOvi R1AR1B, - HC(0) R1AR1B, -N(0)mi, - R1AR1B, -C( 0)R1C, -C(0)-ORlc, -C(0) R1AR1B, -OR1D, - R1AS02R1D, - R1AC(0)R1C, - R1AC(0)0R1C, -N R1A0R1C, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R2 is independently

halogen, -CX23, -CHX22, -CH2X2, -OCX23, -OCH2X2, -OCHX22, -CN, -OH, -NH2, -COOH, -CO NH2, -NO2, -SH, -S03H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC=(0)NHNH2,

-NHC=(0)NH2, -NHSO2H, -NHC=(0)H, -NHC(0)-OH, -NHOH, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

z2 is an integer from 0 to 4;

each R1A, R1B, R1C, and R1D is independently

hydrogen, -CX3, -COOH, -CONH2, -CHX2, -CH2X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;

each X, X1, and X2 is independently -F, -CI, -Br, or -I;

nl is independently an integer from 0 to 4;

ml and vl are independently 1 or 2;

L3, L4, and L5 are independently a bond, -0-, -NH-, -OC(O)-, -C(0)0-, -NHC(O)-, -C(0)NH-, -OC(0)0-, -OC(0)NH-, -NHC(0)0-, -NH C(0)NH-, -S-, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroaryl ene; and

R3 is a detectable moiety.

27. The compound of claim 26 having the formula:

The com ound of claim 26 having the formula:

The compound of claim 26 having the formula:

The compound of claim 26 having the formula:

(Urn).

31. The compound of claim 26 having the formula:


The compound of claim 26 having the formula:


33. The compound of claim 27, wherein W1 is =N-.

34. The compound of claim 27, wherein W1 is =CH-.

35. The compound of claim 27, wherein W2 is =N-

The compound of claim 27, wherein W2 is =CH-

The compound of claim 27, wherein R2 is independently unsubstituted C C3 alkyl.

38. The compound of claim 27, wherein z2 is 0.

39. The compound of claim 27, wherein L1 is -0-.

40. The compound of claim 27, wherein L1 is -OC(O)-.

41. The compound of claim 27, wherein L1 is -OC(0) H-.

42. The compound of claim 27, wherein L1 is a bond.

43. The compound of claim 27, wherein L2 is a substituted or unsubstituted C1-C4 alkyl ene.

44. The compound of claim 27, wherein L2 is an unsubstituted C1-C4 alkylene.

45. The compound of claim 27, wherein L2 is a substituted or unsubstituted C4-C6 cycloalkylene.

46. The compound of claim 27, wherein L2 is a bond.

47. The compound of claim 27, wherein R1 is - R1AR1B, -C(0) R1AR1B, R20-substituted or unsubstituted Ci-C6 alkyl, R20-substituted or unsubstituted 2 to 6 membered heteroalkyl, R20-substituted or unsubstituted C5-C7 cycloalkyl, or R20-substituted or unsubstituted 5 to 7 membered heterocycloalkyl;

R20 is independently oxo,

halogen, -CF3, -CHF2, -CH2F, -OCF3, -OCH2F, -OCHF2, -CN, -OH, - H2, -COOH, -CO H2, -N 02, -SH, -S(0)2CH3, unsubstituted Ci-C6 alkyl, unsubstituted 2 to 6 membered heteroalkyl, unsubstituted C3-C6 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl; and

each R1A and R1B is independently hydrogen, substituted or unsubstituted Ci-C6 alkyl, substituted or unsubstituted 2 to 6 membered heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted 3 to 6 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl; R1A and R1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 5 to 6 membered heterocycloalkyl.

48. The compound of claim 27, wherein R1 is - R1AR1B, -C(0) R1AR1B, or R20-substituted or unsubstituted 6 to 7 membered heterocycloalkyl;

R20 is independently oxo, -OH, -S(0)2CH3; and

each R1A and R1B is independently hydrogen, OH- substituted C1-C4 alkyl, H2-substituted C1-C4 alkyl, or unsubstituted 5 to 6 membered heterocycloalkyl.

49. The compound of claim 27, wherein -L3-L4 -L5 - is -C(0) HCH2CH2CH2 HC(0)Ph-.

50. The compound of claim 27, wherein R3 is a radionuclide.

51. The compound of claim 27, wherein R3 is a positron emitting radionuclide.

52. The compound of claim 27, wherein R3 is carbon-11, nitrogen-13, oxygen-15, or fluorine-18.

53. The compound of claim 27, wherein R3 is fluorine-18 or fluorine-19.

54. The compound of claim 27, wherein R3 is fluorine-18.

55. The compound of claim 27, wherein R3 is gallium-68, zirconium-89, rubidium-82, or iodine-124.

56. The compound of claim 50 having the formula:


57. The compound of claim 50 having the formula:


The com ound of claim 50 having the formula:


The compound of claim 50 having the formula:


60. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of one of claims 1 to 59.

61. A method of treating a disease in a patient in need of such treatment, said method comprising administering a therapeutically effective amount of a compound of one of claims one of claims 1 to 59 to said patient.

62. The method of claim 61, wherein the disease is associated with a cell or organism having an increased Fe11 level compared to a standard control.

63. The method of claim 61, wherein the disease is cancer.

64. The method of claim 61, wherein the disease is malaria.

65. The method of claim 61, wherein the disease is a parasitic disease.

66. A method of detecting a disease associated with a cell or organism having an increased Fe11 level compared to a standard control, in a subject, said method comprising administering an effective amount of a compound of one of claims 27 to 59 to said subject and measuring the level of the compound in the subject.

67. The method of claim 66, comprising measuring the level of compound in the subject using positron emission tomography.

68. The method of claim 66, wherein the disease is cancer, malaria, or an inflammatory disease.