Derivatives of dicarboxylic amino acids and their application in the treatment of neurodegenerative diseases

A process for obtaining a compound of general formula (I)

• wherein,
• R1 represents a hydrogen atom or an aryl, heteroaryl, alkyl, haloalkyl, aminoalkyl, ammoniumalkyl group and, in general, straight or branched alkyl groups, substituted for any chemical group with the express exclusion of alkyl groups substituted by aryl, such as a benzyl group.
• R2, R3 are independently selected from hydrogen, substituted or unsubstituted aryl, heteroaryl, alkyl, carbamate, in which R2 represents —O-aryl or —O-alkyl groups, straight or branched, unsubstituted or substituted for any chemical group, urea derivatives in which R2 represents —NH-aryl or —NH-alkyl groups, straight or branched, unsubstituted or substituted by any chemical group, imides. In general, any chemical group capable of generating the molecule represented in the general formula (I).
• n is 1 or 2.
• C* represents the chiral carbon in amino acids, and may be the R enantiomer, the S enantiomer, or a mixture in any proportion of both enantiomers.
• G1 represents O, N mono or disubstituted, CH2, S or, more generally, any group or chemical structure that can be used as a bond between the amino acid and R4.
• R4 represents any chemical structure combining substituted or unsubstituted alkyl, aryl or heteroaryl groups.
• or an isomer, a pharmaceutically acceptable salt and/or a solvate thereof, said process comprising:
• a) reacting a product of formula (II)
• wherein PG1 is a protecting group of hydroxyl groups and PG2 is a protecting group of amino groups, with an alcohol of formula R1—OH in an anhydrous solvent to obtain compounds of formula (III).
• b) deprotecting a hydroxyl group in the compound of formula (III) by removing the protecting group of hydroxyl groups PG2, to give the compound of formula (IV)
• c) reacting of a compound of formula (IV) with a compound of formula H-G1-R4 in the presence of a coupling agent to give compounds of formula (Ia);
• and optionally, hydrolyzing compound (Ia) in which R2 is a tert-butyloxycarbonyl group by treatment with a strong acid and subsequent acylation of the resulting product by reaction with an acyl chloride of formula R2COCl or an anhydride of formula (R2CO)2O in an anhydrous non-polar solvent.