Methods of using and compositions comprising (-)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide
AssigneeCelgene Corporation
InventorsGeorge W. Muller, Roger Shen-Chu Chen
Life of this patent
Estimating the term…
Abstract
Enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, prodrugs, metabolites, polymorphs, salts, solvates, and clathrates thereof are discussed. Methods of treating and/or preventing various diseases and disorders, such as those ameliorated by the reduction of levels of TNF-α or the inhibition of PDE4, are also disclosed.
Claims46
A method of inhibiting TNF-α production which comprises contacting a cell which produces TNF-α with an effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of inhibiting PDE4 activity which comprises contacting PDE4 with an effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing a disease or a disorder ameliorated by reduction of levels of TNF-α in a patient which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing cancer which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing a disease or disorder ameliorated by the inhibition of PDE4 in a patient which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of controlling cAMP levels in a cell which comprises contacting a cell with an effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing myelodysplastic syndrome in a patient which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing myeloproliferative disease in a patient which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing pain in a patient which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A method of treating or preventing macular degeneration in a patient which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable salt or solvate thereof.
A pharmaceutical composition comprising enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, or a pharmaceutically acceptable metabolite, polymorph, salt, or solvate thereof;
- and a pharmaceutically acceptable carrier, excipient or diluent.
Enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide, substantially free of its (+) isomer, or a pharmaceutically acceptable salt or solvate thereof.
A method of producing enantiomerically pure (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide which comprises:
- (a) contacting (R)-3-amino-3-(3,4-dimethoxyphenyl)propionic acid with phthalic dicarboxaldehyde under conditions sufficient to form (R)-3-(3,4-dimethoxyphenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)propionic acid;
- and
- (b) reducing the (R)-3-(3,4-dimethoxyphenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)propionic acid under conditions sufficient to form (−)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide.
An enantiomerically pure salt of (−)-methyl 3-amino-3-(3,4-dimethoxyphenyl)propionate.
(−)-Methyl 3-amino-3-(3,4-dimethoxyphenyl)propionate N-acetyl-L-phenylalanine salt.
Dependencies are inferred from the claim text.