Anti-cancer agents and uses thereof
First Claim
1. A method of treating a proliferative retinopathy, comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a compound of Formula I:
1 Assignment
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Accused Products
Abstract
The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I:
and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
130 Citations
182 Claims
- 1. A method of treating a proliferative retinopathy, comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a compound of Formula I:
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- 140. A compound of Formula V:
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152. A compound selected from the group consisting of:
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N-[5-(1H-Indol-4-yl)-3′
-methyl-biphenyl-3-yl]-acetamide;N-[5-(1H-Indol-4-yl)-3′
-methyl-biphenyl-3-yl]-methanesulfonamide;N-[5-(1H-Indol-4-yl)-2′
,4′
-difluoro-biphenyl-3-yl]-methane-sulfonamide;N-[5-(1H-Indol-4-yl)-3′
-trifluoromethyl-biphenyl-3-yl]-methane-sulfonamide;N-[5-(1H-Indol-4-yl)-2′
,4′
-difluoro-biphenyl-3-yl]-acetamide;N-[5-(1H-Indol-4-yl)-3′
,4′
-difluoro-biphenyl-3-yl]-acetamide;N-[5-(1H-Indol-4-yl)-3′
-nitro-biphenyl-3-yl]-methanesulfonamide;N-[2′
-Fluoro-5-(1H-indol-4-yl)-5′
-trifluoromethyl-biphenyl-3-yl]-methane-sulfonamide;N-[3-Benzo[1,3]dioxol-5-yl-5-(1H-indol-4-yl)-phenyl]-methane-sulfonamide; and N-[5-(1H-Indol-4-yl)-4′
-trifluoromethyl-biphenyl-3-yl]-acetamide;or a pharmaceutically-acceptable salt or solvate thereof.
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- 153. A compound of Formula I:
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155. A compound selected from the group consisting of:
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[3-(1H-Indol-4-yl)-5-(2-methyl-pyridine-4-carbonyl)-phenyl]-carbamic acid methyl ester; N-[3-(1H-Indol-4-1)-5-(2-morpholin-4-yl-pyridine-4-carbonyl)-phenyl]-methanesulfonamide; N-[3-(1H-Indol-4-yl)-5-(2-methyl-6-morpholin-4-yl-pyridine-4-carbonyl)-phenyl]-methanesulfonamide; N-[3-(2-Dimethylamino-pyridine-4-carbonyl)-5-(1H-indol-4-yl)-phenyl]-methanesulfonamide; N-[3-(1H-Indol-4-yl)-5-(3,4,5,6-tetrahydro-2H-[1,2′
]bipyridinyl-4′
-carbonyl)-phenyl]-methanesulfonamide;N-[3-(1H-Indol-4-yl)-5-(2-methoxy-6-methyl-pyridine-4-carbonyl)-phenyl]-methanesulfonamide; N-[3-(1H-Indol-4-yl)-5-(2-thiomorpholin-4-yl-pyridine-4-carbonyl)-phenyl]-methanesulfonamide; N-[3-(1H-Indol-4-yl)-5-(2-morpholin-4-yl-pyridine-4-carbonyl)-phenyl]-acetamide; N-[3-(1H-indol-4-yl)-5-(2-methyl-6-morpholin-4-yl-pyridine-4-carbonyl)-phenyl]-acetamide; [3-(1H-Indol-4-yl)-5-(2-methyl-6-morpholin-4-yl-pyridine-4-carbonyl)-phenyl]-carbamic acid methyl ester; 2-Hydroxy-N-[3-(H-indol-4-yl)-5-(2-morpholin-4-yl-pyridine-4-carbonyl)-phenyl]-acetamide; 3-(1H-Indol-4-yl)-5-(2-methoxy-pyridine-4-carbonyl)-benzamide; N-[3-(2-Dimethylamino-6-methyl-pyridine-4-carbonyl)-5-(1H-indol-4-yl)-phenyl]-methanesulfonamide, [3-Dimethylamino-5-(1H-indol-4-yl)-phenyl]-(2-dimethylamino-pyridine-4-yl)-methanone; N-[3-(1H-Indol-4-yl)-5-(2-methoxy-pyridine-3-carbonyl)-phenyl]-acetamide; [3-(2-Dimethylamino-6-methyl-pyridine-4-carbonyl)-5-(H-indol-4-yl)-phenyl]-carbamic acid methyl ester; N-[3-(2-Dimethylamino-6-methyl-pyridine-4-carbonyl)-5-(1H-indol-4-yl)-phenyl]-acetamide; and N-[3-(2-Dimethylamino-pyridine-4-carbonyl)-5-(1H-indol-4-yl)-phenyl]-acetamide; or a pharmaceutically-acceptable salt or solvate thereof.
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- 156. A compound of Formula I:
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159. A compound selected from the group consisting of:
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[3′
-(1H-Indol-4-yl)-5-(6-methoxy-pyridin-3-yl)-phenyl]-carbamic acid methyl ester;N-[3-(1H-Indol-4-yl)-5-(6-methoxy-pyridin-3-yl)-phenyl]-methanesulfonamide; 4-[3-Bromo-5-(1H-indol-4-yl)-phenyl]-pyrimidin-2-ylamine; N-[3-(2-Amino-pyrimidin-4-yl)-5-(1H-indol-4-yl)-phenyl]-methanesulfonamide; N-[3-(2-Chloro-pyridin-4-yl)-5-(1H-indol-4-yl)-phenyl]-methanesulfonamide; 3-(2-Amino-pyrimidin-4-yl)-5-(1H-indol-4-yl)-phenol; N-[3-(6-Ethoxy-pyridin-3-yl)-5-(1H-indol-4-yl)-phenyl]-acetamide; N-[3-(2-Chloro-pyridin-4-yl)-5-(1H-indol-4-yl)-phenyl]-acetamide; and N-[3-(6-Chloro-pyridin-3-yl)-5-(1H′
-indol-4-yl)-phenyl]-acetamide;or a pharmaceutically-acceptable salt or solvate thereof.
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Specification