RU95109687A - SUBSTITUTED KURURENINES, METHOD OF THEIR PRODUCTION, USE AS A MEDICINE PREPARATION, PHARMACEUTICAL COMPOSITION - Google Patents

Claims (8)

1. The use of compounds as inhibitors of kinurenine aminotransferase (CAT) for the treatment of cognitive impairment associated with age and generic diseases of the brain. 2. The use according to claim 1, where the compounds that act as inhibitors of kinurenin aminotransferase (CAT) are compounds of formula I:

where R represents halogen, C ₁ - C ₆ -alkyl, C ₅ - C ₇ -cycloalkyl, phenyl-C ₁ -C ₄ -alkyl, C ₁ - C ₆ -alkoxy, C ₆ - C _{1 0} aryloxy, phenyl- C ₁ - C ₄ -alkoxy or trifluoromethyl;
R ₁ is hydroxy, C ₁ - C ₆ -alkoxy, amino, mono-C ₁ - C ₆ -alkylamino, di-C ₁ - C ₆ -alkylamino, hydroxylamino, C ₁ - C ₄ -alkoxyamino or benzyloxyamino,
or as an individual isomer, or as a mixture of isomers and their pharmaceutically acceptable salts. 3. The compound of formula IA

where R represents halogen, C ₁ - C ₆ -alkyl, C ₅ - C ₇ -cycloalkyl, phenyl-C ₁ -C ₄ -alkyl, C ₁ - C ₆ -alkoxy, C ₆ - C _{1 0} aryloxy, phenyl- C ₁ - C ₄ -alkoxy or trifluoromethyl; and
R ₁ is hydroxy, C ₁ - C ₆ -alkoxy, amino, mono-C ₁ - C ₆ -alkylamino, di-C ₁ - C ₆ -alkylamino, hydroxylamino, C ₁ - C ₄ -alkoxyamino or benzyloxyamino,
provided that (i) when R ₁ is hydroxyl and R is a halogen, then this halogen is not fluorine; (ii) when R ₁ is hydroxy and R is C ₁ - C ₆ -alkyl, then this C ₁ - C ₆ -alkyl is not methyl, either as an individual isomer, or as a mixture of isomers and their pharmaceutically acceptable salts. 4. The compounds of formula IA according to claim 3, where R is halogen, C ₁ - C ₆ -alkyl, C ₅ - C ₇ -cycloalkyl; R ₁ is hydroxy,
provided that:
(i) when R is halogen, then this halogen is not fluorine;
and
(ii) when R represents C ₁ - C ₆ -alkyl, then this C ₁ - C ₆ -alkyl is not methyl,
or as an individual isomer, or as a mixture of isomers, and their pharmaceutically acceptable salts.  5. Compounds according to claim 3, selected from the group consisting of: 2-amino-4- (2-amino-5-chlorophenyl) -4-oxobutanoic acid; 2-amino-4- (2-amino-5-ethylphenyl) -4-oxobutanoic acid; 2-amino-4- (2-amino-5-bromophenyl) -4-oxobutanoic acid; 2-amino-4- (2-amino-5-n-propylphenyl) -4-oxobutanoic acid; 2-amino-4- (2-amino-5-isopropylphenyl) -4-oxobutanoic acid; 2-amino-4- (2-amino-5-cyclohexylphenyl) -4-oxobutanoic acid; or as an individual isomer, or as a mixture of isomers, and their pharmaceutically acceptable salts. 6. The method of obtaining the compounds of formula I according to claim 2 or the compounds of formula IA according to claim 3 or its pharmaceutically acceptable salt, characterized in that they carry out 1) the interaction of the compounds of formula II

where R is defined for formula I according to claim 2 or for formula IA according to claim 3,
with chloroacetonitrile to obtain the compounds of formula III

where R is above
2) the interaction of the compounds of formula III with the sodium salt of diethylacetamidine with obtaining the compounds of formula IV

where R is above
3) the interaction of the compounds of formula IV, above,
with concentrated hydrochloric acid to obtain a compound of formula I or IA, where R is indicated above, and R ₁ is hydroxyl, and, if desired, convert the resulting compound of formula I or IA into another compound of formula I or IA with a group R ₁ other than hydroxy , and, if desired, a salt of a compound of formula I or IA is obtained, and, if desired, the isomeric mixture of compound I or IA is separated into individual isomers.  7. A pharmaceutical composition, characterized in that it contains as the active substance a therapeutically effective amount of a compound of formula I according to claim 2, or a compound of formula IA according to claim 3, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier, diluent or carrier.  8. The pharmaceutical composition according to claim 7 for the treatment of cognitive disorders associated with age, and generic diseases of the brain.