Claims
- 1. A compound represented by the following structural formula:
- 2. The compound of claim 1 wherein X is a covalent bond, —C(R4R5)—, —N(R4)—, —O—, C(═O)—, —C(═O)—N(R4)— or —N(R4)—C(═O)— and R3 is a substituted or unsubstituted aryl group.
- 3. The compound of claim 2 wherein R is represented by a structural formula selected from:
- 4. The compound of claim 3 wherein Rings A-F are a substituted or unsubstituted phenyl group; R2 is —H; Z1 is ═O; and X is —C(R4R5)—, —N(R4)— or —O—.
- 5. The compound of claim 4 wherein X is —C(R4R5)—.
- 6. The compound of claim 5 wherein R1 is represented by the following structural formula:
- 7. The compound of claim 6 wherein:
R6 is —H, C1-C4 alkyl, C1-C4 hydroxyalkyl, —(C1-C4 alkylene)—O—(C1-C4 alkylene)-tri(C1-C4 alkyl)silane, —S(O)2N(C1-C4 alkyl)2, —S(O)2NH(C1-C4 alkyl or —S(O)2NH2; R7 and R8 are independently —H, C1-C4 alkyl, C1-C4 hydroxylalkyl, (C1-C4 alkyl)3—Si—O—(C1-C4 alkylene), pyridyl, C1-C4 alkyl substituted with pyridyl, C1-C4 alkyl substituted with —NH-pyridyl, C1-C4 hydroxyalkyl substituted with —NH-pyridyl, C1-C4 hydroxyalkyl substituted with -pyridyl, —S(O)2-(phenyl), —S(O)2-(tolulyl), 91 —C(O)-pyridyl, indolyl, —(C1-C4 alkylene)—O—(C1-C4 alkyl), C1-C4 alkyl substituted with —O-pyridyl, —CHO, —C(O)—O—(C1-C4 alkyl), —C(O)—NH—(C1-C4 alkyl), —C(O)—(C1-C4 alkylene)-pyridyl, oxazolinyl, —C(O)—(C1-C4 alkyl), —C═N—NH-phenyl, —C(O)—NH-pyridyl, —C(O)—NH-phenyl, —C═N—NH—(C1-C4 alkyl), —C═N—N—(C1-C4 alkyl)2, —C(O)—NH—(C1-C4 alkyl), —C(O)—N—(C1-C4 alkyl)2, —C(O)—(N-morphilino), —C(O)-imidazolyl, —C(O)—NH—(C1-C4 haloalkyl), —C(O)—N—(C1-C4 haloalkyl)2, —CH2—N3, C1-C4 alkyl substituted with imidazolyl, —C1-C4 alkylene-NHC(O)—(C1-C4 alkyl), —C1-C4 alkylene-NHC(O)-(phenyl), —(C1-C4 alkylene)-NHC(O)-(tolulyl), —C1-C4-alkylene-NHC(O)-(methoxy, dimethoxy or trimethoxyphenyl); and Y is —S—, —O— or —N(H or C1-C4 alkyl or substituted alkyl)-.
- 8. The compound of claim 7 wherein R4 and R5 are both —H; and R3 is a substituted or unsubstituted phenyl or pyridyl group.
- 9. The compound of claim 8 wherein Rings A and D are unsubstituted or substituted with one or more groups selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN or —NH2.
- 10. The compound of claim 9 wherein R is represented by the following structural formula:
- 11. The compound of claim 10 wherein:
R3 is a phenyl or pyridyl group substituted with zero, one or more groups selected from —Br, —Cl, —F, —Re, —ORe, —CN, —COORe, —N(Re)2, —CON(Re)2, —NReCORf, —NHCONH2 and —SO2 N(Re)2; and each Re and Rf are independently selected from —H, alkyl or substituted alkyl.
- 12. The compound of claim 11 wherein:
R3 is a phenyl group substituted with zero, one or more groups selected from —Cl, —F, —Re, —ORe, —CN, —NH2, —CONH2 or —NHCORf.
- 13. The compound of claim 12 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3.
- 14. The compound of claim 13 wherein R3 is an unsubstituted phenyl group or a phenyl group monosubstituted with —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3, wherein the phenyl group substitutent is at the para position.
- 15. The compound of claim 14 wherein R1 is represented by the following structural formula:
- 16. The compound of claim 15 wherein Ring A is unsubstituted.
- 17. The compound of claim 9 wherein R is represented by the following structural formula:
- 18. The compound of claim 17 wherein R3 is a phenyl or pyridyl group substituted with zero, one or more groups selected from —Br, —Cl, —F, —Re, —ORe, —CN, —COORe, —N(Re)2, —CON(Re)2, —NReCORf, —NHCONH2 and —SO2 N(Re)2; and each Re and Rf are independently selected from —H, alkyl or substituted alkyl.
- 19. The compound of claim 18 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —Cl, —F, —Re, —ORe, —CN, —NH2, —CONH2 or —NHCORf.
- 20. The compound of claim 19 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3.
- 21. The compound of claim 20 wherein R3 is an unsubstituted phenyl group or a phenyl group monosubstituted with —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3, wherein the phenyl group substitutent is at the para position.
- 22. The compound of claim 21 wherein R1 is represented by the following structural formula:
- 23. The compound of claim 22 wherein Ring D is unsubstituted.
- 24. The compound of claim 1 wherein R1 is represented by the following structural formula:
- 25. A compound represented by the following structural formula:
- 26. The compound of claim 25 wherein X is —C(R4R5)—.
- 27. The compound of claim 26 wherein X is —CH2— and Ring G is unsubstituted.
- 28. The compound of claim 25 wherein:
Rings A and D are unsubstituted or substituted with one or more substituents selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN or —NH2; R3 is a phenyl or pyridyl group substituted with zero, one or more groups selected from —Br, —Cl, —F, —Re, —ORe, —CN, —COORe, —N(Re)2, —CON(Re)2, —NReCORf, —NHCONH2 and —SO2 N(Re)2; and each Re and Rf are independently selected from —H, alkyl or substituted alkyl.
- 29. The compound of claim 28 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —Cl, —F, —Re, —ORe, —CN, —NH2, —CONH2 or —NHCORf.
- 30. The compound of claim 29 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —CH3, —CH2CH3, —OCH3, —CN, —F or —Cl.
- 31. A compound represented by the following structural formula:
- 32. A compound represented by the following structural formula:
- 33. A compound represented by the following structural formula:
- 34. A method of treating a subject with cancer comprising the step of administering to the subject an effective amount of a compound represented by the following structural formula:
- 35. The method of claim 33 wherein X is a covalent bond, —C(R4R5)—, —N(R4)—, —O—, —C(═O)—, —C(═O)—N(R4)— or —N(R4)—C(═O)— and R3 is a substituted or unsubstituted aryl group.
- 36. The method of claim 35 wherein R is represented by a structural formula selected from:
- 37. The method of claim 36 wherein Rings A-F are a substituted or unsubstituted phenyl group; R2 is —H; Z1 is ═O; and X is —C(R4R5)—, —N(R4)— or —O—.
- 38. The method of claim 37 wherein X is —C(R4R5)—.
- 39. The method of claim 38 wherein R1 is represented by the following structural formula:
- 40. The method of claim 39 wherein:
R6 is —H, C1-C4 alkyl, C1-C4 hydroxyalkyl, —(C1-C4 alkylene)-O—(C1-C4 alkylene)-tri(C1-C4 alkyl)silane, —S(O)2N(C1-C4 alkyl)2, —S(O)2NH(C1-C4 alkyl or —S(O)2NH2. R7 and R8 are independently —H, C1-C4 alkyl, C1-C4 hydroxylalkyl, (C1-C4 alkyl)3-Si—O—(C1-C4 alkylene), pyridyl, C1-C4 alkyl substituted with pyridyl, C1-C4 alkyl substituted with —NH-pyridyl, C1-C4 hydroxyalkyl substituted with —NH-pyridyl, C1-C4 hydroxyalkyl substituted with -pyridyl, —S(O)2-(phenyl), —S(O)2-(tolulyl), 109 —C(O)-pyridyl, indolyl, —(C1-C4 alkylene)-O—(C1-C4 alkyl), C1-C4 alkyl substituted with —O-pyridyl, —CHO, —C(O)—O—(C1-C4 alkyl), —C(O)—NH—(C1-C4 alkyl), —C(O)—(C1-C4 alkylene)-pyridyl, oxazolinyl, —C(O)—(C1-C4 alkyl), —C═N—NH-phenyl, —C(O)—NH-pyridyl, —C(O)—NH-phenyl, —C═N—NH—(C1-C4 alkyl), —C═N—N—(C1-C4 alkyl)2, —C(O)—NH—(C1-C4 alkyl), —C(O)—N—(C1-C4 alkyl)2, —C(O)— (N-morphilino), —C(O)-imidazolyl, —C(O)—NH—(C1-C4 haloalkyl), —C(O)—N—(C1-C4 haloalkyl)2, —CH2—N3, C1-C4 alkyl substituted with imidazolyl, —C1-C4 alkylene-NHC(O)—(C1-C4 alkyl), —C1-C4 alkylene-NHC(O)-(phenyl), —(C1-C4 alkylene)-NHC(O)-(tolulyl), —C1-C4— alkylene-NHC(O)-(methoxy, dimethoxy or trimethoxyphenyl); and Y is —S—, —O— or —N(H or C1-C4 alkyl or substituted alkyl)-.
- 41. The method of claim 40 wherein R4 and R5 are both —H; and R3 is a substituted or unsubstituted phenyl or pyridyl group.
- 42. The method of claim 41 wherein Rings A and D are unsubstituted or substituted with one or more groups selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN or —NH2.
- 43. The method of claim 42 wherein R is represented by the following structural formula:
- 44. The method of claim 43 wherein:
R3 is a phenyl or pyridyl group substituted with zero, one or more groups selected from —Br, —Cl, —F, —R3, —ORe, —CN, —COORe, —N(Re)2, —CON(Re)2, —NReCORf, —NHCONH2 and —SO2 N(Re)2; and each Re and Rf are independently selected from —H, alkyl or substituted alkyl.
- 45. The method of claim 44 wherein:
R3 is a phenyl group substituted with zero, one or more groups selected from —Cl, —F, —Re, —ORe, —CN, —NH2, —CONH2 or —NHCORf.
- 46. The method of claim 45 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3.
- 47. The method of claim 46 wherein R3 is an unsubstituted phenyl group or a phenyl group monosubstituted with —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3, wherein the phenyl group substitutent is at the para position.
- 48. The method of claim 47 wherein R1 is represented by the following structural formula:
- 49. The method of claim 48 wherein Ring A is unsubstituted.
- 50. The method of claim 42 wherein R is represented by the following structural formula:
- 51. The method of claim 49 wherein R3 is a phenyl or pyridyl group substituted with zero, one or more groups selected from —Br, —Cl, —F, —Re, —OR, —CN, —COORe, —N(Re)2, —CON(Re)2, —NReCORf, —NHCONH2 and —SO2 N(Re)2;
and each Re and Rf are independently selected from —H, alkyl or substituted alkyl.
- 52. The method of claim 51 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —Cl, —F, —Re, —ORe, —CN, —NH2, —CONH2 or —NHCORf.
- 53. The method of claim 52 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3.
- 54. The method of claim 53 wherein R3 is an unsubstituted phenyl group or a phenyl group monosubstituted with —CH3, —CH2CH3, —F, —Cl, —CN or —OCH3, wherein the phenyl group substitutent is at the para position.
- 55. The method of claim 54 wherein R1 is represented by the following structural formula:
- 56. The method of claim 55 wherein Ring D is unsubstituted.
- 57. The method of claim 34 wherein R1 is represented by the following structural formula:
- 58. A method of treating a subject with cancer wherein the method comprises administering to the subject an effective amount of a compound represented by the following structural formula:
- 59. The method of claim 58 wherein X is —C(R4R5)—.
- 60. The method of claim 59 wherein X is —CH2— and Ring G is unsubstituted.
- 61. The method of claim 58 wherein:
Rings A and D are unsubstituted or substituted with one or more substituents selected from —F, —Cl, —Br, —C1-C4 alkyl, C1-C4 alkoxy, —C1-C4 haloalkyl, C1-C4 haloalkoxy, —CN or —NH2; R3 is a phenyl or pyridyl group substituted with zero, one or more groups selected from —Br, —Cl, —F, —Re, —ORe, —CN, —COORe, —N(Re)2, —CON(Re)2, —NReCORf, —NHCONH2 and —SO2 N(Re)2; and each Re and Rf are independently selected from —H, alkyl or substituted alkyl.
- 62. The method of claim 61 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —Cl, —F, —Re, —ORe, —CN, —NH2, —CONH2 or —NHCORf.
- 63. The method of claim 61 wherein R3 is a phenyl group substituted with zero, one or more groups selected from —CH3, —CH2CH3, —OCH3, —CN, —F or —Cl.
- 64. A method of treating a subject with cancer wherein the method comprises administering to the subject an effective amount of a compound represented by the following structural formula:
- 65. A method of treating a subject with cancer wherein the method comprises administering to the subject an effective amount of a compound represented by the following structural formula:
- 66. The method of claim 34 wherein the cancer is multi-drug resistant.
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/322,105, filed Sep. 13, 2001, the entire teachings of which are incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60322105 |
Sep 2001 |
US |