Novel cyclodextrin derivatives, method for the preparation thereof and use thereof for the solubilization of pharmacologically active substances

A process for the preparation of a compound of formula (I)

• in which:
• n represents an integer from 1 to 6;
• m represents an integer equal to 5, 6 or 7;
• R1 represents either an OH group or an —S—CH2—(CH2)n—Z group, the R1 groups all being identical;
• Z represents either:
• an NHX group,
• a quatemary ammonium group of the +NX3 form,
• a
• group,
• X representing a hydrogen atom or an alkyl group comprising from 1 to 6 carbon atoms, and in particular being a methyl, ethyl, propyl or butyl group, and
• R representing a hydrogen atom, a linear or branched alkyl substituent with 1 to 12 carbon atoms, or an aromatic group such as the phenyl, benzyl or naphthyl group, or derivatives of these groups carrying substituents on the aromatic ring such as methyl, ethyl, chlorine, bromine, iodine, nitro, hydroxyl, methoxyl or acetamido substituents,
• or R representing a biorecognition element such as an amino acid derivative, a peptide, a monosaccharide, an oligosaccharide, a multiplication element with several branchings comprising glucidic groups which can be
• identical or different, or a visualization probe or fluorescent or radioactive detection probe,
• said process being characterized in that it comprises the following stages:
• the reaction of a compound selectively or totally halogenated in primary alcohol position, of the following formula (VII):
• m being as defined above,
• W representing an OH group or a Y group, the W groups all being identical,
• and Y representing a halogen atom chosen from the group constituted by chlorine, bromine, iodine, and preferably being bromine or iodine,
• with an ω-aminoalkanethiol of the following formula (VIII):
• said ω-aminoalkanethiol optionally being N-alkylated,
• or the corresponding salt of the following formula (VIII-a):
• or a tetraalkylamnmonium salt of the following formula (VIII-b):
• said salt being associated with a halide counter ion, preferably the chloride ion,
• n and X being as defined above, and X preferably being a hydrogen atom,
• the compound of formula (VIII) preferably being cysteamine of formula H2N—CH2—CH2—SH,
• in order to obtain a compound of formula (I) as defined above and having the following formulae (A-a) or (A-b):
• and optionally
• the reaction of the compound of formula (A-a) as obtained in the preceding stage with an isothiocyanate of the following formula (IX):
• R—N═C═S (IX)
• in which R is as defined above,
• in order to obtain a compound of formula (I) as defined above, and corresponding to the following formula:

A compound of the following general formula:

• in which:
• n represents an integer from 1 to 6;
• m represents an integer equal to 5, 6 or 7;
• R1 represents either an OH group or an —S—CH2—(CH2)n—Z group, the R1 groups all being identical;
• Z represents either:
• an NHX group,
• a quaternary ammonium group of the +NX3 form,
• a
• group,
• X representing a hydrogen atom or an alkyl group comprising from 1 to 6 carbon atoms, and being in particular a methyl, ethyl, propyl or butyl group, and
• R representing a hydrogen atom, a linear or branched alkyl substituent with 1 to 12 carbon atoms, or an aromatic group such as the phenyl, benzyl or naphthyl group, or derivatives of these groups carrying substituents on the aromatic ring such as methyl, ethyl, chlorine, bromine, iodine, nitro, hydroxyl, methoxyl or acetamido substituents,
• or R representing a biorecognition element such as an amino acid derivative, a peptide, a monosaccharide, an oligosaccharide, a multiplication element with several branchings comprising glucidic groups which can be identical or different, or a visualization probe or fluorescent or radioactive detection probe,
• provided that the compound in which n=1, m=6, Z=NH2 and R1=OH is excluded.