2-(2,4,5-substituted aniline) pyrimidine derivative, pharmaceutical composition and use thereof
View Patent ↗Disclosed are a 2-(2,4,5-substituted aniline) pyrimidine derivative, a pharmaceutical composition and a use thereof. The pharmaceutical composition comprises a therapeutically effective amount of the 2-(2,4,5-substituted aniline) pyrimidine derivative, a solvate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Also disclosed is a use of the 2-(2,4,5-substituted aniline) pyrimidine derivative, a solvate, or a pharmaceutically acceptable salt thereof in the preparation of drugs for treating cancers. The compounds of the present invention have a relatively high solubility in water and a relatively high permeability, and/or a relatively low binding ability to plasma proteins, and at the same time have a relatively low toxicity characteristic and a relatively high anti-tumor activity.
1. A 2-(2,4,5-substituted aniline)pyrimidine derivative, solvate, or pharmaceutically acceptable salt thereof selected from the group consisting of
N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-(D 3 -methyl)indol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;
N-(2-{2-dimethylaminoethyl-methylamino}-4-(D 3 -methoxy)-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;
N-(2-{2-dimethylaminoethyl-(D 3 -methyl)amino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;
N-(2-{2-di(D 3 -methyl)aminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide; and
N-(2-{2-[methyl(D 3 -methyl)amino]ethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamid,
wherein the D 3 -methyl or D 3 -methoxy substituents comprise deuterium at a percentage higher than the natural abundance of deuterium.
2. The 2-(2,4,5-substituted aniline)pyrimidine derivative, solvate, or pharmaceutically acceptable salt thereof according to claim 1 , wherein the pharmaceutically acceptable salt includes a salt of an inorganic acid and a salt of an organic acid; the salt of the inorganic acid being hydrochloride, hydrobromide, hydriodate, sulfate, phosphate, or a salt of hydrogen disulfide; the salt of the organic acid being p-toluene sulfonate, salicylate, tartrate, hydrogen tartrate, ascorbate, maleate, benzene sulfonate, fumarate, gluconate, glucuronate, formate, glutamate, mesylate, esylate, benzene sulfonate, lactate, oxalate, brosylate, carbonate, citrate, benzoate, malate or acetate.
3. A method for treating lung cancer in a subject in need thereof, the method comprising administering an effective amount of the 2-(2,4,5-substituted aniline)pyrimidine derivative, solvate, or pharmaceutically acceptable salt thereof according to claim 1 , to the subject.
4. The method according to claim 3 , wherein the lung cancer is non small-cell lung cancer.