RU2003130635A - APPLICATION OF N-PHENYL-2-PYRIMIDINAMINE DERIVATIVES AGAINST THE DISEASES BASED ON THE MASTOCYTES, SIMILAR TO ALLERGIC DISORDERS - Google Patents

Claims (14)

1. The use of a derivative of N-phenyl-2-pyrimidinamine of the formula I

where R ₁ means 4-pyrazinyl; 1-methyl-1H-pyrrolyl; amino or phenyl substituted with amino lower alkyl wherein the amino group in each case is free, alkylated or acylated; 1H-indolyl or 1H-imidazolyl attached at the carbon atom of the five-membered ring; or unsubstituted or lower alkyl substituted pyridyl attached at the ring carbon atom and unsubstituted or substituted at the nitrogen atom with oxygen; R ₂ and R ₃ mean each independently of the other hydrogen or (ness.) Alkyl; one or two of the radicals R ₄ , R ₅ , R ₆ , R ₇ and R ₈ mean each nitro, fluoro-substituted (ness.) alkoxy or a radical of the formula II

where R ₉ means hydrogen or (ness.) alkyl, X means oxo, thio, imino, N- (ness.) Alkylimino, hydroxyimino or O- (ness.) Alkylhydroximino, Y is oxygen or an NH group, N is 0 or 1, and R ₁₀ means an aliphatic radical having at least 5 carbon atoms, or an aromatic, aromatic-aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, heterocyclic or heterocyclic-aliphatic radical, and the remaining radicals R ₄ , R ₅ , R ₆ , R ₇ and R ₈ are each independently of the other hydrogen, (lower alkyl.) alkyl which is unsubstituted or substituted by free or alkylated amino, piperazinyl, piperidinyl, pyrrolidinyl or by morpholinyl, or (lower alkyl.) alkanoyl tiftormetil free, ether or complicated oefirny hydroxy, free, alkylated or acylated amino or free or esterified carboxy, or a salt of such a compound containing at least one salt-forming group, with the aim of obtaining a medicine for the treatment of allergic rhinitis, allergic dermatitis, drug allergy or food allergy, angioedema, urticaria, sudden death syndrome of an apparently healthy child, bronchopulmonary aspergillosis, mastocytosis or multiple sclerosis. 2. The use of the compounds according to claim 1, where one or two of the radicals R ₄ , R ₅ , R ₆ , R ₇ and R ₈ mean each nitro or a radical of formula II, where R ₉ means hydrogen or (ness.) alkyl, X means oxo, thio, imino, N- (ness.) Alkylimino, hydroxyimino or O- (ness.) Alkylhydroximino, Y is oxygen or an NH group, n is 0 or 1, and R ₁₀ means an aliphatic radical containing at least 5 carbon atoms, or an aromatic, aromatic-aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, heterocyclic or heterocyclic-aliphatic radical, and the remaining radicals R ₄ , R ₅ , R ₆ , R ₇ and R ₈ mean each independently hydrogen, lower alkyl, which is unsubstituted or substituted by a free or alkylated amino group, piperazinyl, piperidinyl, pyrrolidinyl or morpholinyl, or (lower) alkanoyl, trifluoromethyl, a free, ether or ester hydroxy group, a free, alkylated or acylated amino group or a free or esterified carboxy group, and the remaining substituents are as defined in claim 1, or a pharmaceutically acceptable salt of such a compound containing at least one salt-forming group. 3. The use of the compounds of formula I according to claim 1, where R ₁ means pyridyl bonded to a carbon atom, R ₂ , R ₃ , R ₅ , R ₆ and R _{8 are} each hydrogen, R ₄ means (ness.) Alkyl, R ₇ means a radical of formula II, where R ₉ means hydrogen, X means oxo, n is 0, and R ₁₀ means 4-methylpiperazinylmethyl, or a pharmaceutically acceptable salt thereof. 4. The use of the compounds of formula I according to claim 1, which is N- {5- [4- (4-methylpiperazinomethyl) benzoylamido] -2-methylphenyl} -4- (3-pyridyl) -2-pyrimidinamine, or a pharmaceutically acceptable salt thereof. 5. The use of the compounds of formula I according to one of claims 1 to 4, where the compound is used in the form of its monomesylate salt. 6. The use of the compounds of formula I according to claim 5 in the preparation of a medicament for the treatment of mast cells in dogs. 7. A method of treating warm-blooded mammals suffering from allergic rhinitis, allergic dermatitis, drug allergy or food allergy, angioedema, urticaria, sudden death syndrome of an apparently healthy child, bronchopulmonary aspergillosis, mastocytosis or multiple sclerosis, comprising administering to the mammal a compound of formula I, one of claims 1 to 4, in an amount that is therapeutically effective against at least one of the diseases mentioned above, where the compounds of formula I can also be present in the form of a pharmaceutically acceptable salt thereof. 8. The method according to claim 7, where the compound of formula I is used in the form of its monomesylate salt. 9. A method of treating dogs suffering from canine mast cell tumors, which comprises administering to said dog in need of such treatment an effective dose for a canine mast cell tumor of a compound of formula I as defined in one of claims 1 to 4. 10. The method according to claim 9, where the compound of formula I is used in the form of its monomesylate salt. 11. The method according to claim 9, where the daily dose of 20-200 mg of 4- (4-methylpiperazin-1-ylmethyl) -N- [4-methyl-3- (4-pyridin-3-yl) pyrimidin-2-ylamino ) phenyl] benzamide or a pharmaceutically acceptable salt thereof is administered to an adult dog. 12. The method according to claim 10, where the daily dose of 20-200 mg of the monomesylate salt of 4- (4-methylpiperazin-1-ylmethyl) -N- [4-methyl-3- (4-pyridin-3-yl) pyrimidin-2 -amylamino) phenyl] benzamide is administered to an adult dog. 13. The method according to claim 7, where the daily dose of 30-750 mg of 4- (4-methylpiperazin-1-ylmethyl) -N- [4-methyl-3- (4-pyridin-3-yl) pyrimidin-2-ylamino ) phenyl] benzamide or a pharmaceutically acceptable salt thereof is administered to a human. 14. The method according to item 13, where the daily dose is 30-600 mg of 4- (4-methylpiperazin-1-ylmethyl) -N- [4-methyl-3- (4-pyridin-3-yl) pyrimidin-2- ilamino) phenyl] benzamide or a pharmaceutically acceptable salt thereof.