Methods and compositions for the prevention and treatment of atherosclerosis, restenosis and related disorders
AssigneeCelgene Corporation
InventorJerome B. Zeldis
Life of this patent
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Abstract
Methods and compositions for the prevention and treatment of all forms of atherosclerosis are described. Administration of compounds such as thalidomide, its analogs, hydrolysis products, metabolites, derivatives and precursors as well as additional compounds capable of inhibiting tumor necrosis factor α (TNF-α) are used in the invention. Also disclosed is the coating of prosthetic devices, such as stents, with the compounds of the invention for the prevention and/or treatment of restenosis.
Claims42
A method of preventing atherosclerosis in a mammal comprising administering to a mammal an effective amount of a TNF-α inhibitor selected from the group consisting of:
- cyano and carboxy derivatives of substituted styrenes;
- cyclic imides;
- cycloalkyl amides and cycloalkyl nitrites;
- aryl amides;
- 1-oxo-2-(2,6-dioxo-3-fluoropiperidin-3yl) isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidine-3-yl) isoindolines;
- tetra substituted 2-(2,6-dioxopiperdin-3-yl)-1-oxoisoindolines;
- imide/amide ethers and alcohols;
- succinimides and maleimides;
- 1-oxo-and 1,3 dioxo-2-(2,6-dioxopiperidin-3-yl) isoindolines substituted with amino in the benzo ring;
- imido and amido substituted alkanohydroxamic acids;
- substituted phenethylsulfones substituted to the phenyl group with an oxoisoindine group;
- 1-Oxo and 1,3 dioxo-2-(2,6-dioxopiperidin-3yl) isoindolines;
- non-polypeptide cyclic amides;
- imido and amido substituted alkanohydroxamic acids;
- and substituted phenethylsulfones.
A method of preventing atherosclerosis in a mammal comprising administering to a mammal an effective amount of a TNF-α inhibitor selected from the group consisting of:
- 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline, 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)4-aminoisoindoline and 3-(3,4-dimethoxyphenyl)-3-(1-oxisoindolin-2-yl)propionamide.
A method of preventing atherosclerosis in a mammal comprising administering to a mammal an effective amount of a TNF-α inhibitor selected from the group consisting of thalidomide, its analogs, its hydrolysis products, its metabolites and its precursors.
A method of treating atherosclerosis in a mammal comprising administering to a mammal in need thereof an effective amount of a TNF-α inhibitor selected from the group consisting of:
- cyano and carboxy derivatives of substituted styrenes;
- cyclic imides;
- cycloalkyl amides and cycloalkyl nitrites;
- aryl amides;
- 1-oxo-2-(2,6-dioxo-3-fluoropiperidin-3yl) isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidine-3-yl) isoindolines;
- tetra substituted 2-(2,6-dioxopiperdin-3-yl)-1-oxoisoindolines;
- imidelamide ethers and alcohols;
- succinimides and maleimides;
- 1-oxo-and 1,3 dioxo-2-(2,6-dioxopiperidin-3-yl) isoindolines substituted with amino in the benzo ring;
- imido and amido substituted alkanohydroxamic acids;
- substituted phenethylsulfones substituted to the phenyl group with an oxoisoindine group;
- 1-Oxo and 1,3 dioxo-2-(2,6-dioxopiperidin-3 yl) isoindolines;
- non-polypeptide cyclic amides;
- imido and amido substituted alkanohydroxamic acids and substituted phenethylsulfones.
A method of treating atherosclerosis in a mammal comprising administering to a mammal in need thereof an effective amount of a TNF-α inhibitor selected from the group consisting of:
- 1-oxo-2-(2,6-dioxopiperidin-3-yl)4-aminoisoindoline;
- 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline;
- and 3-(3,4-dimethoxyphenyl)-3-(1-oxisoindolin-2-yl)propionamide.
A method of treating atherosclerosis in a mammal comprising administering to a mammal in need thereof an effective amount of a TNF-α inhibitor selected from the group consisting of thalidomide, its analogs, its hydrolysis products, its metabolites and its precursors.
A method of inhibiting or preventing restenosis in a mammal comprising administering to a mammal in need thereof an effective amount of a TNF-α inhibitor selected from the group consisting of:
- cyano and carboxy derivatives of substituted styrenes;
- cyclic imides;
- cycloalkyl amides and cycloalkyl nitrites;
- aryl amides;
- 1-oxo-2-(2,6-dioxo-3-fluoropiperidin-3yl) isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidine-3-yl) isoindolines;
- tetra substituted 2-(2,6-dioxopiperdin-3-yl)-1-oxoisoindolines;
- imide/amide ethers and alcohols (for example 3-Phthalimido-3-(3′,4′-dimethoxypheryl)propan-1-ol);
- succinimides and maleimides;
- 1-oxo- and 1,3 dioxo-2-(2,6-dioxopiperidin-3-yl) isoindolines substituted with amino in the benzo ring;
- imido and amido substituted alkanohydroxamic acids;
- substituted phenethylsulfones substituted to the phenyl group with an oxoisoindine group;
- 1-Oxo and 1,3 dioxo-2-(2,6-dioxopiperidin-3yl) isoindolines;
- non-polypeptide cyclic amides;
- imido and amido substituted alkanohydroxamic acids;
- and
- substituted phenethylsulfones.
A method of inhibiting or preventing restenosis in a mammal comprising administering to a mammal in need thereof an effective amount of a drug selected from the group consisting of:
- 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline;
- 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline;
- and 3-(3,4-dimethoxyphenyl)-3-(1-oxisoindolin-2-yl)propionamide so that restenosis is prevented or reduced.
A method of inhibiting or preventing restenosis in a mammal comprising administering to a mammal in need thereof an effective amount of a TNF-α inhibitor selected from the group consisting of thalidomide, its analogs, its hydrolysis products, its metabolites and its precursors so that restenosis is prevented or reduced.
A prosthetic device suitable for implantation or use in a mammal wherein said device is coated on at least one surface with a therapeutically effective amount of a TNF-α inhibitor selected from the group consisting of:
- cyano and carboxy derivatives of substituted styrenes;
- cyclic imides;
- cycloalkyl amides and cycloalkyl nitrites;
- aryl amides;
- 1-oxo-2-(2,6-dioxo-3-fluoropiperidin-3yl) isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidine-3-yl) isoindolines;
- tetra substituted 2-(2,6-dioxopiperdin-3-yl)-1-oxoisoindolines;
- imide/amide ethers and alcohols;
- succinimides and maleimides propionate;
- 1-oxo-and 1,3 dioxo-2-(2,6-dioxopiperidin-3-yl) isoindolines substituted with amino in the benzo ring;
- imido and amido substituted alkanohydroxamic acids;
- substituted phenethylsulfones substituted to the phenyl group with an oxoisoindine group;
- 1-Oxo and 1,3 dioxo-2-(2,6-dioxopiperidin-3 yl) isoindolines;
- non-polypeptide cyclic amides;
- imido and amido substituted alkanohydroxamic acids and substituted phenethylsulfones.
A prosthetic device suitable for implantation or use in a mammal wherein said device is coated on at least one surface with a therapeutically effective amount of a composition comprising:
- 1-oxo-2-(2,6-dioxopiperidin-3-yl)4-aminoisoindoline;
- 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline;
- and 3-(3,4-dimethoxyphenyl)-3-(1-oxisoindolin-2-yl)propionamide so that restenosis is prevented or reduced.
A prosthetic device suitable for implantation or use in a mammal wherein said device is coated on at least one surface with a therapeutically effective amount of thalidomide, its analogs, its hydrolysis products, its metabolites or its precursors.
A method for the production of a prosthetic device coated with a composition comprising compounds which inhibit TNF-α selected from the group consisting of:
- cyano and carboxy derivatives of substituted styrenes;
- cyclic imides;
- cycloalkyl amides and cycloalkyl nitrites;
- aryl amides;
- 1-oxo-2-(2,6-dioxo-3-fluoropiperidin-3yl) isoindolines and 1,3-dioxo-2-(2,6-dioxo-3-fluoropiperidine-3-yl) isoindolines;
- tetra substituted 2-(2,6-dioxopiperdin-3-yl)-1-oxoisoindolines;
- imide/amide ethers and, alcohols;
- succinimides and maleimides propionate;
- 1-oxo-and 1,3 dioxo-2-2,6-dioxopiperidin-3-yl) isoindolines substituted with amino in the benzo ring;
- imido and amido substituted alkanohydroxamic acids;
- substituted phenethylsulfones substituted to the phenyl group with an oxoisoindine group;
- 1-Oxo and 1,3 dioxo-2-(2,6-dioxopiperidin-3 yl) isoindolines;
- non-polypeptide cyclic amides;
- imido and amido substituted alkanohydroxamic acids and substituted phenethylsulfones
- comprising dipping, spraying, casting, layering or impregnating the device with a suspension of the compounds.
A method for the production of a prosthetic device coated with a composition comprising compounds which inhibit TNF-α selected from the group consisting of:
- 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline;
- 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)4-aminoisoindoline;
- and
- 3-(3,4-dimethoxyphenyl)-3-(1-oxisoindolin-2-yl)propionamide comprising dipping, spraying, casting, layering or impregnating the device with a suspension of the compounds.
A method for the production of a prosthetic device coated with a composition comprising compounds which inhibit TNF-α selected from the group consisting of:
- thalidomide, its analogs, its hydrolysis products, its metabolites and its precursors comprising dipping, spraying, casting, layering or impregnating the device with a suspension of the compounds.
Dependencies are inferred from the claim text.