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US 2006/0148804 A1Published application
Pde4 inhibitors for the treatment of neoplasms of lymphoid cells
OwnerJurgen Braunger, Christian Schudtinventors
Life of this patent
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Abstract
The invention relates to the use of certain PDE4 inhibitors alone or in combination with one or more differentiation inducing agents and/or an agent effective in raising intracellular concentrations of cAMP or a stable analogue of cAMP in the preparation of pharmaceutical compositions for the treatment of neoplasms of lymphoid cells.
Claims34
-38. (canceled)
A method of treating neoplasms of lymphoid cells in a mammal, comprising administering to said mammal a therapeutically effective amount of a compound selected from the group consisting of
- N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018), 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490,
- and pharmaceutically acceptable salts thereof.
13 more elements
A method for treating neoplasms of lymphoid cells in a mammal, comprising administering to said mammal therapeutically effective amounts of
- (i) a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018], 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490,
- and pharmaceutically acceptable salts thereof,
- and (ii) one or more differentiation inducing agents and/or an agent effective in raising intracellular concentrations of cAMP or a stable analogue thereof.
14 more elements
A method for treating neoplasms of lymphoid cells in a mammal, comprising administering to said mammal therapeutically effective amounts of
- (i) a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018], 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490,
- and pharmaceutically acceptable salts thereof,
- and (ii) one or more differentiation inducing agents.
14 more elements
A method for treating neoplasms of lymphoid cells in a mammal, comprising administering to said mammal therapeutically effective amounts of
- (i) a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018], 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490,
- and pharmaceutically acceptable salts thereof,
- and (ii) an agent effective in raising intracellular concentrations of cAMP or a stable analogue thereof.
14 more elements
(canceled)
-61. (canceled)
A treatment combination for neoplasms of lymphoid cells, comprising:
- therapeutically effective amounts of
- (i) a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018], 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490
- and pharmaceutically acceptable salts thereof,
- and (ii) one or more differentiation inducing agents and/or an agent effective in raising intracellular concentrations of cAMP or a stable analogue of cAMP.
15 more elements
A treatment combination for neoplasms of lymphoid cells, comprising:
- therapeutically effective amounts of
- (i) a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018], 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490
- and pharmaceutically acceptable salts thereof,
- and (ii) one or more differentiation inducing agents.
15 more elements
A treatment combination for neoplasms of lymphoid cells, comprising:
- therapeutically effective amounts of
- (i) a compound selected from the group consisting of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide [INN:
- PICLAMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)-benzamide [INN:
- ROFLUMILAST], 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro-1-oxy-pyrid-4-yl)-benzamide (Roflumilast-N-Oxide), 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3H-purine [Research Code:
- V-11294A], N-[9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydropyrrolo[3,2,1-jk][1,4]benzo-diazepin-3(R)-yl]pyridine-4-carboxamide [Research Code:
- CI-1018], 3,7-dihydro-3-(4-chlorophenyl)-1-propyl-1H-purine-2,6-dione [INN:
- AROFYLLINE], N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-281], N-(3,5-dichloropyridin-4-yl)-2-[5-fluoro-1-(4-fluorobenzyl)-1H-indol-3-yl]-2-oxoacetamide [Research Code:
- AWD-12-343], Tetrahydro-5-[4-methoxy-3-[(1S,2S,4R)-2-norbornyloxy]phenyl]-2(1H)-pyrimidone [INN:
- ATIZORAM];
- β-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide [Research Code:
- CDC-801], Methanesulfonic acid 2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzo-furan-6-yl ester [INN:
- LIRIMILAST], 3,5-dichloro-4-[8-methoxy-2-(trifluoromethyl)quinolin-5-ylcarbox-amido]pyridine-1-oxide [Research Code:
- SCH-351591], cis-4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl]cyclohexane-1-carboxylic acid [INN:
- Cilomilast],
- a compound with the research code CDC-998, D-4396, IC-485, CC-1088 or KW4490
- and pharmaceutically acceptable salts thereof,
- and (ii) an agent effective in raising intracellular concentrations of cAMP or a stable analogue of cAMP.
15 more elements
-74. (canceled)
(canceled)
Dependencies are inferred from the claim text.