3-3-di-substituted-oxindoles as inhibitors of translation initiation
AssigneePresident and Fellows of Harvard College
InventorsJosé A. Halperin, Amarnath Natarajan, Huseyin Aktas, Yun-Hua Fan, Han Chen
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Abstract
Compositions and methods for inhibiting translation using 3-(5-tert-Butyl-2-Hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one and/or its derivatives are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, and/or (4) disorders associated with viral infections, using 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one and/or its derivatives are described.
Claims13
A method of inhibiting translation initiation in a cell comprising contacting the cell with a compound of formula III, formula IV, formula VI, or formula VIII wherein
- the compound of formula III is:
- wherein X is oxygen, NH or CH2;
- and
- R is 3′-CH2CH(CO2Me)NH2, 3′-CH2CH(CO2Me)NHFmoc, 3′-t-Bu, 3′-OH, 3′-O(CH2)3CHCH2, 3′-O(CH2)4Br, 3′-O(CH2)4NMe2, 3′-O(CH2)4N3,
- 3′-O(CH2)4NH2, 3′-CF3, 3′-CH3, 3′-n-heptyl, 3′-n-nonyl, 3′-i-Bu, 3′-i-propyl, 3′-n-propyl, 3′-n-octyl, 3′-Et, 3′-n-pentyl, 3′-n-Bu, 3′-n-hexyl, 3′-n-cyclopentyl, 3′-n-cyclohexyl, 4-NHSO2(4-tBu)Ph or 3′-NHSO2(4-tBu)Ph;
- the compound of formula IV is:
- wherein R is 4-F, 4-O(CH2)3CHCH2, 3-Cl, 3-F, 3-Me, 2-Me or 2-OMe;
- the compound of formula VI is:
- wherein R1 is 7-Br, 4-Cl, 5-Br, 5-NO2, 5-I, 5-OMe, 5-Cl, 7-CF3, 5-NH2, 4-Br, 6-Br, H, 7-OMe, 7-I, 5-Et, 7-Et, 4-Et, 6-Et, 5-F, 5-N3, 7-COOH, 7-CO2H, 4-Cl, 6-Cl or 5-NHSO2-1-napthyl;
- and
- R2 is H or 7-CO2H;
- and
- the compound of formula VIII is:
- wherein R1 is H or 7-CO2H;
- R2 is H, 2-Me, 3′-Me, 3-F or 3-CF3;
- and
- R3 is H, 2-NHFmoc, 2-NHSO2CH2Ph, 2-NHSO2CH3, 2-NHSO2(4-tBu)Ph, 2-NHSO2(4-NHAc)Ph, 2-NHSO2(3-CF3)Ph, 2-NHSO2(4-NO2)Ph, 2-NHSO2(4-OMe)Ph, 2-NHSO2(4-Br)Ph, 2-NHSO2(4-I)Ph, 2-NHSO2(4-Ph)Ph, 2-NHSO2(4-OPh)Ph, 2-NHAc, 2-NHCO(4-tBu)Ph or 3′-NHSO2(4-tBu)Ph.
A method of inhibiting translation initiation in a cell comprising contacting the cell with 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.
A method of inhibiting translation initiation in a cell in a human or non-human mammal comprising administering to the human or non-human mammal 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.
A method of inhibiting translation initiation in a cell comprising contacting the cell with a compound of formula XV,
- wherein X is oxygen, NH or CH2;
- R1 is 3′-CH2CH(CO2Me)NH2, 3′-CH2CH(CO2Me)NHFmoc, 3′-t-Bu, 3′-OH, 3′-O(CH2)3CHCH2, 3′-O(CH2)4Br, 3′-O(CH2)4NMe2, 3′-O(CH2)4N3, 3′
- 3′-O(CH2)4NH2, 3′-CF3, 3′-CH3, 3′-n-heptyl, 3′-n-nonyl, 3′-i-Bu, 3′-i-propyl, 3′-n-propyl, 3′-n-octyl, 3′-Et, 3′-n-pentyl, 3′-n-Bu, 3′-n-hexyl, 3′-n-cyclopentyl, 3′-n-cyclohexyl, 4-NHSO2(4-tBu)Ph or 3′-NHSO2(4-tBu)Ph;
- R2 is H, 4-F, 4-O(CH2)3CHCH2, 3-Cl, 3-F, 3-Me, 2-Me or 2-OMe;
- R3 is H, 7-Br, 4-Cl, 5-Br, 5-NO2, 5-I, 5-OMe, 5-Cl, 7-CF3, 5-NH2, 4-Br, 6-Br, H, 7-OMe, 7-I, 5-Et, 7-Et, 4-Et, 6-Et, 5-F, 5-N3, 7-COOH, 7-CO2H, 4-Cl, 6-Cl or 5-NHSO2-1-napthyl;
- and
- R4 is H or 7-CO2H.
Dependencies are inferred from the claim text.