Antitumoral analogs of et-743
Antitumour compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins. They have at the C-1 position a substituent selected from an optionally protected or derivatised aminomethylene group or an optionally protected or derivatised hydroxymethylene group.
1. A compound of the formula:
wherein:
R′ is selected from the group consisting of —CH 2 —N(R a ) 2 and —CH 2 —OR a ,
where R a is selected from the group consisting of H; alkyl-CO—; haloalkyl-CO—; cycloalkylalkyl-CO—; haloalkyl-O—CO—; arylalkyl-CO—; arylalkenyl-CO—; heteroaryl-CO—; alkenyl-CO—; alkeny; and amino acid acyl;
R 5 is —OR″, where R″ is selected from the group consisting of H; alkyl-CO—; cycloalkyl—CO—; and haloalkyl-CO—;
R 18 is —OR, where R is selected from the group consisting of H, alkyl-CO—; and cycloalkylalkyl—CO—; and
R 21 is —OH;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , which is of the formula:
wherein R 1 , R 5 , R 18 , and R 21 are as defined in claim 1 .
3. The compound of claim 1 , wherein R 1 is —CH 2 —NHR a .
4. The compound of claim 1 , wherein R a is -aa-R b where aa is amino acid acyl and R b is as defined for R a .
5. The compound of claim 4 , wherein said amino acid acyl is further substituted with at least one R a group.
6. The compound of claim 4 , wherein R 1 is —CH 2 —NH-aa-R b where aa is an amino acid and R b is selected from the group consisting of hydrogen; arylalkenyl-CO—; haloalkyl-CO—; alkyl-CO—; arylalkyl-CO—; and amino acid acyl.
7. The compound of claim 6 , wherein R 1 is —CH 2 —NH-aa-R b where aa is alanine and R b is selected from the group consisting of hydrogen, CF 3 CO—, trifluoromethylcinnamoyl, cinnamoyl, C 3 F 7 CO—, butyryl, 3-chloroproprionoyl, hydrocinnamoyl, hexanoyl, phenylacetyl, and acetyl.
8. The compound of claim 5 , wherein R 1 is —CH 2 —NR a -aa-R b where aa is an amino acid, R a is alkyl-CO— and R b is haloalkyl-CO—.
9. The compound of claim 8 , wherein R 1 is —CH 2 —NR a -aa-R b where aa is acetylalanine, R a is selected from the group consisting of acetyl and butyryl, and R b is CF 3 —CO—.
10. The compound of claim 3 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, alkyl-CO—; alkenyl-CO—; arylalkenyl-CO—; arylalkyl-CO—; heteroaryl-CO—; cycloalkylalkyl-CO—; and alkenyl.
11. The compound of claim 10 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexylpropionyl and allyl.
12. The compound of claim 1 , wherein R′ is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; alkyl-CO—; arylalkyl-CO—; and arylalkenyl-CO—.
13. The compound of claim 12 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; cinnamoyl.
14. The compound of claim 5 , wherein R 5 is —OR″, where R″ is selected from the group consisting of H; alkyl-CO where the alkyl has an odd number of carbon atoms, and ω-cyclohexylalkyl-CO.
15. The compound of claim 14 , wherein R 5 is —OCOCH 3 .
16. The compound of claim 15 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexylpropionyl and allyl.
17. The compound of claim 15 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
18. The compound of claim 1 , wherein R 18 is —OR, where R is selected from the group consisting of H and alkyl-CO.
19. The compound of claim 18 , wherein R 18 is —OH.
20. The compound of claim 19 , wherein R 5 is —OCOCH 3 .
21. The compound of claim 19 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexylpropionyl and allyl.
22. A compound of a formula selected from the following general structures I, II and III:
wherein R′, X 2 , R 1 and R 6 are each independently selected from the groups defined below:
R′
X 2
R 1
R 6
H
OH
OH
OH
CH 2 CH═CH 2
OAc
OAc
COCH 2 CH 3
OCH 2 CH═CH 2
OMOM
COCH 2 CH 2 CH 3
OCOOCH 2 CH═CH 2
OCOCH 2 C 6 H 11
CO(CH 2 ) 4 CH 3
OCOCF 3
OCOCH 2 CH 2 C 6 H 11
CO(CH 2 ) 12 CH 3
OCOCH 2 Cl
OCOCH 2 CH 2 CH 3
CO(CH 2 ) 16 CH 3
OCOCH 2 CH 2 Cl
OCO(CH 2 ) 4 CH 3
COCH 2 C 6 H 11
OCOCF 2 CF 2 CF 3
OCO(CH 2 ) 8 CH 3
COCH 2 CH 2 C 6 H 11
OCO(CH 2 ) 16 CH 3
COOCH 2 CCl 3
COCH 2 Ph
COCH 2 CH 2 Ph
COCH═CHCH 3
COCH═CHPh
COCH═CHArCF 3
COCH(CH 3 )NHCOCH 2 CH 2 Ph
CO—(S)—CH(CH 3 )NHCOCF 3
CO—(R)—CH(CH 3 )NHCOCF 3
CO—(S)—CH(NHCbz)CH(CH 3 ) 2
Boc
CSNHPh
or a pharmaceutically acceptable salt thereof.
23. A compound which is selected from the following formulae:
or a pharmaceutically acceptable salt thereof.
24. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
25. A compound of the formula:
or a pharmaceutically acceptable salt thereof.
26. A pharmaceutical composition comprising a compound of the formula:
wherein:
R 1 is selected from the group consisting of —CH 2 —N(R a ) 2 and —CH 2 —OR a ,
where R a is selected from the group consisting of H; alkyl-CO—; haloalkyl-CO—; cycloalkylalkyl-CO—; haloalkyl-O-CO—; arylalkyl-CO—; arylalkenyl-CO—; heteroaryl-CO—; alkenyl-CO—; alkenyl and amino acid acyl;
R 5 is —OR″, where R″ is selected from the group consisting of H; alkyl-CO—; cycloalkyl-CO—; and haloalkyl-CO—;
R 18 is —OR, where R is selected from the group consisting of H, alkyl-CO—; and cycloalkylalkyl-CO—; and
R 21 is —OH;
or a pharmaceutically acceptable salt thereof;
together with a pharmaceutical acceptable carrier.
27. The composition of claim 26 , wherein said compound is of the formula:
wherein R 1 , R 5 , R 18 , and R 21 are as defined as in claim 26 ;
or a pharmaceutically acceptable salt thereof.
28. The composition of claim 26 , wherein R 1 is —CH 2 —NHR a .
29. The composition of claim 26 , wherein R a is -aa-R b where aa is amino acid acyl and R b is as defined for R a .
30. The composition of claim 29 , wherein said amino acid acyl is further substituted with at least one R a group.
31. The composition of claim 29 , wherein R 1 is —CH 2 —NH-aa-R b where aa is an amino acid and R b is selected from the group consisting of hydrogen; arylalkenyl-CO—; haloalkyl-CO—; alkyl-CO—; arylalkyl-CO—; and amino acid acyl.
32. The composition of claim 31 , wherein R 1 is —CH 2 —NH-aa-R b where aa is alanine and R b is selected from the group consisting of hydrogen, CF 3 CO—, trifluoromethylcinnamoyl, cinnamoyl, C 3 F 7 CO—, butyryl, 3-chloroproprionoyl, hydrocinnamoyl, hexanoyl, phenylacetyl, and acetyl.
33. The composition of claim 30 , wherein R 1 is —CH 2 —NR a -aa-R b where aa is an amino acid, R a is alkyl-CO— and R b is haloalkyl-CO—.
34. The composition of claim 33 , wherein R 1 is —CH 2 —NR a -aa-R b where aa is acetylalanine, R a is selected from the group consisting of acetyl and butyryl and R b is CF 3 —CO—.
35. The composition of claim 28 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, alkyl-CO—; alkenyl-CO—; arylalkenyl-CO—; arylalkyl-CO—; heteroaryl-CO—; cycloalkylalkyl-CO—; and alkenyl.
36. The composition of claim 35 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexyipropionyl and allyl.
37. The composition of claim 26 , wherein R′ is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; alkyl-CO—; arylalkyl-CO—; and arylalkenyl-CO—.
38. The composition of claim 37 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
39. The composition of claim 26 , wherein R 5 is —OR″, where R″ is selected from the group consisting of H; alkyl-CO where the alkyl has an odd number of carbon atoms, and ω-cyclohexylalkyl—CO—.
40. The composition of claim 39 , wherein R 5 is —OCOCH 3 .
41. The composition of claim 40 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexylpropionyl and allyl.
42. The composition of claim 40 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
43. The composition of claim 26 , wherein R 18 is —OR, where R is selected from the group consisting of H and alkyl-CO—.
44. The composition of claim 43 , wherein R 18 is —OH.
45. The composition of claim 44 , wherein R 5 is —OCOCH 3 .
46. The composition of claim 44 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexylpropionyl and allyl.
47. The composition of claim 44 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
48. A composition comprising a compound of a formula selected from the following general structures I, II and III:
wherein R′, X 2 , R 1 and R 6 are each independently selected from the groups defined below:
R′
X 2
R 1
R 6
H
OH
OH
OH
CH 2 CH═CH 2
OAc
OAc
COCH 2 CH 3
OCH 2 CH═CH 2
OMOM
COCH 2 CH 2 CH 3
OCOOCH 2 CH═CH 2
OCOCH 2 C 6 H 11
CO(CH 2 ) 4 CH 3
OCOCF 3
OCOCH 2 CH 2 C 6 H 11
CO(CH 2 ) 12 CH 3
OCOCH 2 Cl
OCOCH 2 CH 2 CH 3
CO(CH 2 ) 16 CH 3
OCOCH 2 CH 2 Cl
OCO(CH 2 ) 4 CH 3
COCH 2 C 6 H 11
OCOCF 2 CF 2 CF 3
OCO(CH 2 ) 8 CH 3
COCH 2 CH 2 C 6 H 11
OCO(CH 2 ) 16 CH 3
COOCH 2 CCl 3
COCH 2 Ph
COCH 2 CH 2 Ph
COCH═CHCH 3
COCH═CHPh
COCH═CHArCF 3
COCH(CH 3 )NHCOCH 2 CH 2 Ph
CO—(S)—CH(CH 3 )NHCOCF 3
CO—(R)—CH(CH 3 )NHCOCF 3
CO—(S)—CH(NHCbz)CH(CH 3 ) 2
Boc
CSNHPh
or a pharmaceutically acceptable salt thereof;
together with a pharmaceutically acceptable carrier.
49. A composition comprising a compound which is selected from the following formulae:
or a pharmaceutically acceptable salt thereof;
together with a pharmaceutically acceptable carrier.
50. A composition comprising a compound of the formula
together with a pharmaceutically acceptable carrier;
or a pharmaceutically acceptable salt thereof.
51. A composition comprising a compound of the formula:
together with a pharmaceutically acceptable carrier;
or a pharmaceutically acceptable salt thereof.
52. A method of treating a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound of the formula:
wherein:
R 1 selected from the group consisting of —CH 2 —N(R a ) 2 and —CH 2 —OR a ,
where R a is selected from the group consisting of H; alkyl-CO—; haloalkyl-CO—; cycloalkylalkyl-CO—; haloalkyl-O—CO—; arylalkyl-CO—; arylalkenyl-CO—; heteroaryl-CO—; alkenyl-CO—; alkeny; and amino acid acyl;
R 5 is —OR″, where R″ is selected from the group consisting of H; alkyl-CO—; cycloalkyl-CO—; and haloalkyl-CO—;
R 18 is —OR, where R is selected from the group consisting of H, alkyl-CO—; and cycloalkylalkyl-CO—;
R 21 is —OH;
or a pharmaceutically acceptable salt thereof.
53. The method of claim 52 , wherein said mammal is a human.
54. The method of claim 53 , wherein said compound is administered by intravenous infusion.
55. The method of claim 52 , wherein said compound of formula:
is administered as part of a combination therapy.
56. The method of claim 52 , wherein said compound is of the formula:
wherein R 1 , R 5 , R 18 , and R 21 are as defined as in claim 52 .
57. The method of claim 52 , wherein R 1 is —CH 2 —NHR a .
58. The method of claim 52 , wherein R a is -aa-R b where aa is amino acid acyl and R b is as defined for R a .
59. The method of claim 58 , wherein said amino acid acyl is further substituted with at least one R a group.
60. The method of claim 58 , wherein R 1 is —CH 2 —NH-aa-R b where aa is an amino acid and R b is selected from the group consisting of hydrogen; arylalkenyl-CO—; haloalkyl-CO—; alkyl-CO—; arylalkyl-CO—; and amino acid acyl.
61. The method of claim 60 , wherein R 1 is —CH 2 —NH-aa-R b where aa is alanine and R b is selected from the group consisting of hydrogen, CF 3 CO—, trifluorocinnamoyl, cinnamoyl, C 3 F 7 CO—, butyryl, 3-chloroproprionoyl, hydrocinnamoyl, hexanoyl, phenylacetyl, and acetyl.
62. The method of claim 59 , wherein R 1 is —CH 2 —NR a -aa-R b where aa is an amino acid, R a is alkyl-CO— and R b is haloalkyl-CO—.
63. The method of claim 62 , wherein R 1 is —CH 2 —NR a -aa-R b where aa is acetylalanine, R a is selected from the group consisting of acetyl and butyryl and R b is CF 3 -CO—.
64. The method of claim 57 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, alkyl-CO—; alkenyl-CO—; arylalkenyl-CO—; arylalkyl-CO—; heteroaryl-CO—; cycloalkylalkyl-CO—; and alkenyl.
65. The method of claim 64 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexyipropionyl and allyl.
66. The method of claim 52 , wherein R′ is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; alkyl-CO—; arylalkyl-CO—; and arylalkenyl—CO—.
67. The method of claim 66 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
68. The method of claim 52 , wherein R 5 is —OR″, where R″ is selected from the group consisting of H; alkyl-CO where the alkyl has an odd number of carbon atoms, and ω-cyclohexylalkyl-CO—.
69. The method of claim 68 , wherein R 5 is —OCOCH 3 .
70. The method of claim 69 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexylpropionyl and allyl.
71. The method of claim 69 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
72. The method of claim 52 , wherein R 18 is —OR, where R is selected from the group consisting of H, and alkyl-CO—.
73. The method of claim 72 , wherein R 18 is —OH.
74. The method of claim 73 , wherein R 5 is —OCOCH 3 .
75. The method of claim 74 , wherein R 1 is —CH 2 —NHR a where R a is selected from the group consisting of hydrogen, acetyl, isovaleroyl, decanoyl, cinnamoyl, hydrocinnamoyl, phenylacetyl, propionyl, myristoyl, stearoyl, hexanoyl, crotonyl, chloronicotinoyl, cyclohexylacetyl, cyclohexyipropionyl and allyl.
76. The method of claim 73 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
77. A method of treating a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound selected from the following general structures I, II and III:
wherein R′, X 2 , R 1 and R 6 are each independently selected from the groups defined below:
R′
X 2
R 1
R 6
H
OH
OH
OH
CH 2 CH═CH 2
OAc
OAc
COCH 2 CH 3
OCH 2 CH═CH 2
OMOM
COCH 2 CH 2 CH 3
OCOOCH 2 CH═CH 2
OCOCH 2 C 6 H 11
CO(CH 2 ) 4 CH 3
OCOCF 3
OCOCH 2 CH 2 C 6 H 11
CO(CH 2 ) 12 CH 3
OCOCH 2 Cl
OCOCH 2 CH 2 CH 3
CO(CH 2 ) 16 CH 3
OCOCH 2 CH 2 Cl
OCO(CH 2 ) 4 CH 3
COCH 2 C 6 H 11
OCOCF 2 CF 2 CF 3
OCO(CH 2 ) 8 CH 3
COCH 2 CH 2 C 6 H 11
OCO(CH 2 ) 16 CH 3
COOCH 2 CCl 3
COCH 2 Ph
COCH 2 CH 2 Ph
COCH═CHCH 3
COCH═CHPh
COCH═CHArCF 3
COCH(CH 3 )NHCOCH 2 CH 2 Ph
CO—(S)—CH(CH 3 )NHCOCF 3
CO—(R)—CH(CH 3 )NHCOCF 3
CO—(S)—CH(NHCbz)CH(CH 3 ) 2
Boc
CSNHPh
or a pharmaceutically acceptable salt thereof.
78. A method of treating a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound which is selected from the following formulae:
or a pharmaceutically acceptable salt thereof.
79. A method of treating a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
80. A method of treatment a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof.
81. The compound of claim 19 , wherein R 1 is —CH 2 —OR a where R a is selected from the group consisting of hydrogen; butyryl; trifluoromethylcinnamoyl; and cinnamoyl.
82. The method of claim 52 , wherein the cancer is leukemia, lung cancer, colon cancer, melanoma, kidney cancer, prostate cancer, lymphoma, breast cancer, or ovarian cancer.
83. The method of claim 77 , wherein the cancer is leukemia, lung cancer, colon cancer, melanoma, kidney cancer, prostate cancer, lymphoma, breast cancer, or ovarian cancer.
84. The method of claim 78 , wherein the cancer is leukemia, lung cancer, colon cancer, melanoma, kidney cancer, prostate cancer, lymphoma, breast cancer, or ovarian cancer.
85. The method of claim 79 , wherein the cancer is leukemia, lung cancer, colon cancer, melanoma, kidney cancer, prostate cancer, lymphoma, breast cancer, or ovarian cancer.
86. The method of claim 80 , wherein the cancer is leukemia, lung cancer, colon cancer, melanoma, kidney cancer, prostate cancer, lymphoma, breast cancer, or ovarian cancer.
87. A compound of a formula selected from the following general structures I, II and III:
wherein R′, X 2 , R 1 and R 6 are each independently selected from the groups defined below:
R′
X 2
R 1
R 6
COCH 2 CH 2 CH 3
OH
OH
OH
COCH═CHPh
OAc
OAc
COCH═CHArCF 3
OCH 2 CH═CH 2
OMOM
CO—(S)—CH(CH3)NHCOCF 3
OCOOCH 2 CH═CH 2
OCOCH 2 C 6 H 11
OCOCF 3
OCOCH 2 CH 2 C 6 H 11
OCOCH 2 Cl
OCOCH 2 CH 2 CH 3
OCOCH 2 CH 2 Cl
OCO(CH 2 ) 4 CH 3
OCOCF 2 CF 2 CF 3
OCO(CH 2 ) 8 CH 3
OCO(CH 2 ) 16 CH 3
or a pharmaceutically acceptable salt thereof.
88. A compound which is selected from the following formulae:
or a pharmaceutically acceptable salt thereof.
89. A composition comprising a compound of a formula selected from the following general structures I, II and III:
wherein R′, X 2 , R 1 and R 6 are each independently selected from the groups defined below:
R′
X 2
R 1
R 6
COCH 2 CH 2 CH 3
OH
OH
OH
COCH═CHPh
OAc
OAc
COCH═CHArCF 3
OCH 2 CH═CH 2
OMOM
CO—(S)—CH(CH3)NHCOCF 3
OCOOCH 2 CH═CH 2
OCOCH 2 C 6 H 11
OCOCF 3
OCOCH 2 CH 2 C 6 H 11
OCOCH 2 Cl
OCOCH 2 CH 2 CH 3
OCOCH 2 CH 2 Cl
OCO(CH 2 ) 4 CH 3
OCOCF 2 CF 2 CF 3
OCO(CH 2 ) 8 CH 3
OCO(CH 2 ) 16 CH 3
or a pharmaceutically acceptable salt thereof; together with a pharmaceutically acceptable carrier.
90. A composition comprising a compound which is selected from the following formulae:
or a pharmaceutically acceptable salt thereof; together with a pharmaceutically acceptable carrier.
91. A method of treating a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound selected from the following general structures I, II and III:
wherein R′, X 2 , R 1 and R 6 are each independently selected from the groups defined below;
R′
X 2
R 1
R 6
COCH 2 CH 2 CH 3
OH
OH
OH
COCH═CHPh
OAc
OAc
COCH═CHArCF 3
OCH 2 CH═CH 2
OMOM
CO—(S)—CH(CH3)NHCOCF 3
OCOOCH 2 CH═CH 2
OCOCH 2 C 6 H 11
OCOCF 3
OCOCH 2 CH 2 C 6 H 11
OCOCH 2 Cl
OCOCH 2 CH 2 CH 3
OCOCH 2 CH 2 Cl
OCO(CH 2 ) 4 CH 3
OCOCF 2 CF 2 CF 3
OCO(CH 2 ) 8 CH 3
OCO(CH 2 ) 16 CH 3
or a pharmaceutically acceptable salt thereof.
92. A method of treating a mammal affected by bladdar cancer, breast cancer, colon cancer, stomach cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, throat cancer, prostate cancer, kidney cancer, retinoblastoma, melanoma, fibrosarcoma, chondrosarcoma, osteosarcoma, leukemia, or lymphoma, which comprises administering to the affected mammal a therapeutically effective amount of a compound which is selected from the following formulae:
or a pharmaceutically acceptable salt thereof.