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Abstract
The present invention provides new compounds of formula Ia and Ib: as well as a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy.
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Citations
49 Claims
- 1. A compound of formula Ia or Ib,
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9. A compound selected from the group consisting of:
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2-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]isonicotinamide;
2-Hydroxy-3-{4-[(4-methylpiperazin-1-yl)carbonyl]pyridin-2-yl}-1H-indole-5-carbonitrile hydrochloride;
2-Hydroxy-3-{5-[(4-methylpiperazin-1-yl)carbonyl]pyridin-2-yl}-1H-indole-5-carbonitrile;
2-Hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride;
2-Hydroxy-3-[6-(2-morpholin-4-ylethoxy)pyrimidin-4-yl]-1H-indole-5-carbonitrile;
2-Hydroxy-3-{5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl}-1H-indole-5-carbonitrile hydrochloride;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]-N-methylnicotinamide hydrochloride;
2-Hydroxy-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carbonitrile hydrochloride;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochloride;
2-Hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile;
2-Hydroxy-3-[5-(pyrrolidin-1-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile hydrochloride;
2-Hydroxy-3-{5-[(4-methyl-1,4-diazepan-1-yl)methyl]pyridin-2-yl}-1H-indole-5-carbonitrile hydrochloride;
2-Hydroxy-3-{5-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]pyridin-2-yl}-1H-indole-5-carbonitrile hydrochloride;
3-(5-{[3-(Dimethylamino)pyrrolidin-1-yl]methyl}pyridin-2-yl)-2-hydroxy-1H-indole-5-carbonitrile;
2-Hydroxy-3-{5-[(4-methylpiperidin-1-yl)methyl]pyridin-2-yl}-1H-indole-5-carbonitrile;
2-Hydroxy-3-{5-[(4-phenylpiperazin-1-yl)methyl]pyridin-2-yl}-1H-indole-5-carbonitrile;
3-[5-(Azetidin-1-ylmethyl)pyridin-2-yl]-2-hydroxy-1H-indole-5-carbonitrile;
2-Hydroxy-3-[5-({4-[2-nitro-4-(trifluoromethyl)phenyl]piperazin-1-yl}methyl)pyridin-2-yl]-1H-indole-5-carbonitrile;
3-(5-{[(2-Cyanoethyl)(ethyl)amino]methyl}pyridin-2-yl)-2-hydroxy-1H-indole-5-carbonitrile;
3-(5-{[(4-Chlorobenzyl)(methyl)amino]methyl}pyridin-2-yl)-2-hydroxy-1H-indole-5-carbonitrile;
3-(5-{[(2-Furylmethyl)(methyl)amino]methyl}pyridin-2-yl)-2-hydroxy-1H-indole-5-carbonitrile;
2-Hydroxy-3-(5-{[methyl(phenyl)amino]methyl}pyridin-2-yl)-1H-indole-5-carbonitrile;
2-Hydroxy-3-{5-[(3-methylpiperidin-1-yl)methyl]pyridin-2-yl}-1H-indole-5-carbonitrile;
3-(5-{[Cyclohexyl(methyl)amino]methyl}pyridin-2-yl)-2-hydroxy-1H-indole-5-carbonitrile;
2-Hydroxy-3-[5-(piperidin-1-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile;
3-{5-[(4-Methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indol-2-ol hydrochloride;
6-Chloro-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indol-2-ol hydrochloride;
3-[5-(Morpholin-4-ylcarbonyl)pyridin-2-yl]-5-nitro-1H-indol-2-ol;
6-Bromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride;
2-Hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-6-carbonitrile hydrochloride;
5-Bromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride;
5,6-Dibromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride;
3-Fluoro-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-2-oxoindoline-6-carbonitrile hydrochloride;
3-{5-[(4-Benzylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-2-hydroxy-1H-indole-5-carbonitrile hydrochloride;
2-Hydroxy-3-(5-{[4-(3-methylbutyl)piperazin-1-yl]sulfonyl}pyridin-2-yl)-1H-indole-5-carbonitrile hydrochloride;
2-Hydroxy-3-{5-[(4-isopropylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carbonitrile hydrochloride;
3-{5-[(4-Ethylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-2-hydroxy-1H-indole-5-carbonitrile hydrochloride;
3-[5-(Morpholin-4-ylmethyl)pyridin-2-yl]-5-pyridin-3-yl-1H-indol-2-ol;
3-[5-(Morpholin-4-ylmethyl)pyridin-2-yl]-5-thien-2-yl-1H-indol-2-ol hydrochloride;
5-(2-Furyl)-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol hydrochloride;
3-{3-Bromo-5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-5-nitro-1H-indol-2-ol hydrochloride;
3-[5-(Morpholin-4-ylmethyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-indol-2-ol hydrochloride;
2-Hydroxy-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-6-carbonitrile hydrochloride;
N-[(1-Ethylpyrrolidin-2-yl)methyl]-6-(2-hydroxy-5-nitro-1H-indol-3-yl)nicotinamide hydrochloride;
6-(2-Hydroxy-5-nitro-1H-indol-3-yl)-N-(2-morpholin-4-ylethyl)nicotinamide hydrochloride;
6-(2-Hydroxy-5-nitro-1H-indol-3-yl)-N-methyl-N-(1-methylpiperidin-4-yl)nicotinamide hydrochloride;
5-Nitro-3-{5-[(4-pyrrolidin-1-ylpiperidin-1-yl)carbonyl]pyridin-2-yl}-1H-indol-2-ol hydrochloride;
3-(5-{[3-(Dimethylamino)pyrrolidin-1-yl]carbonyl}pyridin-2-yl)-5-nitro-1H-indol-2-ol hydrochloride;
N-[2-(Dimethylamino)-1-methylethyl]-6-(2-hydroxy-5-nitro-1H-indol-3-yl)nicotinamide hydrochloride;
6-(2-Hydroxy-5-nitro-1H-indol-3-yl)-N-(2-pyrollindin-1-ylethyl)nicotinamide fumarate;
3-{5-[(4-Methylpiperazin-1-yl)carbonyl]pyridin-2-yl}-5-nitro-1H-indol-2-ol fumarate;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-(2-pyrrolidin-1-ylethyl)nicotinamide fumarate;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide hydrochloride;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]pyridine-3-sulfonamide fumarate;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]-N-ethylpyridine-3-sulfonamide fumarate;
6-(5-Cyano-2-hydroxy-1H-indol-3-yl)-N-[(1-ethylpyrrolidin-2-yl)methyl]pyridine-3-sulfonamide fumarate;
2-Hydroxy-3-{5-[(4-methyl-1,4-diazepan-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carbonitrile fumarate;
2-Hydroxy-3-[5-(morpholin-4-ylsulfonyl)pyridin-2-yl]-1H-indole-5-carbonitrile;
3-{5-[(4-Methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-5-(2-methyl-1,3-thiazol-4-yl)-1H-indol-2-ol hydrochloride;
3-{5-[(4-Methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-5-(1,3-thiazol-4-yl)-1H-indol-2-ol fumarate;
3-{5-[(4-Methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-5-(1,3-oxazol-5-yl)-1H-indol-2-ol; and
3-[5-(Morpholin-4-ylmethyl)pyridin-2-yl]-5-nitro-1H-indol-2-ol hydrochloride.
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11. (canceled)
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12. (canceled)
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13. (canceled)
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14. (canceled)
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15. (canceled)
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16. (canceled)
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17. (canceled)
- 25. A compound according to formula XXV,
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27. A compound selected from the group consisting of:
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1-[(6-Chloropyridin-3-yl)methyl]-4-methylpiperazine;
2-Chloro-5-(morpholin-4-ylmethyl)pyridine 1-oxide;
2-Chloro-5-(pyrrolidin-1-ylmethyl)pyridine 1-oxide;
1-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-4-methyl-1,4-diazepane;
2-Chloro-5-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]pyridine 1-oxide;
1-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-N,N-dimethylpyrrolidin-3-amine;
2-Chloro-5-[(4-methylpiperidin-1-yl)methyl]pyridine 1-oxide;
1-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-4-phenylpiperazine;
1-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-4-[2-nitro-4-(trifluoromethyl)phenyl]piperazine;
3-[[(6-Chloro-1-oxidopyridin-3-yl)methyl](ethyl)amino]propanenitrile;
N-(4-Chlorobenzyl)-N-[(6-chloro-1-oxidopyridin-3-yl)methyl]-N-methylamine;
N-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-N-(2-furylmethyl)-N-methylamine;
N-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-N-methyl-N-phenylamine;
5-(Azetidin-1-ylmethyl)-2-chloropyridine 1-oxide;
2-Chloro-5-[(3-methylpiperidin-1-yl)methyl]pyridine 1-oxide;
N-[(6-Chloro-1-oxidopyridin-3-yl)methyl]-N-cyclohexyl-N-methylamine; and
2-Chloro-5-(piperidin-1-ylmethyl)pyridine 1-oxide.
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- 28. A compound according to formula B,
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30. A compound selected from the group consisting of:
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2-Chloro-N-[2-(dimethylamino)ethyl]isonicotinamide;
1-(2-Chloroisonicotinoyl)-4-methylpiperazine;
6-Chloro-N-[2-(dimethylamino)ethyl]-N-methylnicotinamide;
4-{2-[(6-Chloropyrimidin-4-yl)oxy]ethyl}morpholine;
1-Benzyl-4-[(6-chloropyridine-3-yl)sulfonyl]piperazine;
1-[(6-Chloropyridin-3-yl)sulfonyl]-4-(3-methylbutyl)piperazine;
1-[(6-Chloropyridin-3-yl)sulfonyl]-4-isopropylpiperazine;
1-[(6-Chloropyridin-3-yl)sulfonyl]-4-ethylpiperazine;
1-[(5-Bromo-6-chloropyridin-3-yl)sulfonyl]-4-methylpiperazine;
6-Chloro-N-methyl-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide;
6-Chloro-N-[2-(dimethylamino)ethyl]pyridine-3-sulfonamide;
6-Chloro-N-[2-(dimethylamino)ethyl]-N-ethylpyridine-3-sulfonamide;
6-Chloro-N-[(1-ethylpyrrolidin-2-yl)methyl]pyridine-3-sulfonamide;
1-[(6-Chloropyridin-3-yl)sulfonyl]-4-methyl-1,4-diazepane; and
4-[(6-Chloropyridin-3-yl)sulfonyl]morpholine.
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- 31. A compound according to formula C,
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33. A compound selected from the group consisting of:
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5,6-Dibromo-1,3-dihydroindol-2-one;
5-Pyridin-3-yl-1,3-dihydro-2H-indol-2-one;
5-Thien-2-yl-1,3-dihydro-2H-indol-2-one;
5-(2-Furyl)-1,3-dihydro-2H-indol-2-one;
5-(1,3-Oxazol-5-yl)-1,3-dihydro-2H-indol-2-one;
5-(1,3-Thiazol-4-yl)-1,3-dihydro-2H-indol-2-one; and
5-(2-Methyl-1,3-thiazol-4-yl)-1,3-dihydro-2H-indol-2-one.
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- 34. A compound according to formula XXVII
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36. A compound selected from the group consisting of:
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Ethyl 6-(2-hydroxy-5-nitro-1H-indol-3-yl)nicotinate; and
Ethyl 6-(2-hydroxy-5-cyano-1H-indol-3-yl)nicotinate;
as a free base or a salt thereof.
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- 37. A compound of formula XXVIII.
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39. A compound selected from the group consisting of:
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3-[5-(Morpholin-4-ylmethyl)-1-oxidopyridin-2-yl]-5-pyridin-3-yl-1H-indol-2-ol;
3-[5-(Morpholin-4-ylmethyl)-1-oxidopyridin-2-yl]-5-thien-2-yl-1H-indol-2-ol; and
5-(2-Furyl)-3-[5-(morpholin-4-ylmethyl)-1-oxidopyridin-2-yl]-1H-indol-2-ol. wherein the compound is in the form of a free base or a salt thereof.
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40. A compound selected from the group consisting of:
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5-(Hydroxymethyl)-1,3-dihydro-2H-indol-2-one;
2-Oxoindoline-5-carbaldehyde; and
5-(Chloroacetyl)-1,3-dihydro-2H-indol-2-one;
wherein the compound is in the form of a free base or a salt thereof.
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41. (canceled)
Specification