EP0167449A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
New ganglioside derivatives
Assignee: Fidia SpA
•
Filing: 1985-06-26
•
Granted: —
•
Expires: 2005-06-26
Abstract
Abstract New functional ganglioside derivatives comprising ester, amide and peracylated derivatives of gangliosides, preparation procedures therefor, pharmaceutical preparations containing the same, and the therapeutic use of the derivatives.
Inventors
- 👤 Francesco Della Valle
- 👤 Aurelio Romeo
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-05 15:11
CPC Classifications
C; C07; C07H; C07H3/00; C07H15/00; C07H15/02; C07H15/04; C07H15/10; A; A61; A61P; A61P25/00
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
150 words
- A ganglioside derivative of a ganglioside, said ganglioside being comprised of an oligosaccharide portion, at least one ceramide residue and at least one sialic acid residue, said ganglioside derivative being selected from the group consisting of an ester of the carboxylic groups of said sialic acide residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; an amide of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acide residues may optionally be peracylated; and a peracylated derivative of said hydroxyl groups wherein said sialic acid residues have free carboxyl groups, with the proviso that said ganglioside derivative is not the methyl ester of the ganglioside G M1 or the peracylated derivatives thereof, the methyl ester of the ganglioside GM3 or the peracylated derivative thereof.
Claim 2
Dependent Claim
150 words
- A ganglioside derivative of a ganglioside, said ganglioside being comprised of an oligosaccharide portion, at least one ceramide residue and at least one sialic acid residue, said ganglioside derivative being selected from the group consisting of an ester of the carboxylic groups of said sialic acide residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; an amide of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acide residues may optionally be peracylated; and a peracylated derivative of said hydroxyl groups wherein said sialic acid residues have free carboxyl groups, with the proviso that said ganglioside derivative is not the methyl ester of the ganglioside G M1 or the peracylated derivatives thereof, the methyl ester of the ganglioside GM3 or the peracylated derivative thereof.
Claim 3
Dependent Claim
122 words
- A ganglioside derivative as in claim 1, wherein the oligosaccharide is formed of a maximum of 4 hexoses selected from the group consisting of glucose and galactose or of N-acetylhexoseamines selected frorn the group consisting of N-acetylglucosamine and N-acetylgalactosamine there being present at least one hexose residue, and in which the oligosaccharide is unitary as to its chemical structure, and in which the ceramide residue derives from an aggregation of acylsphingosines which arc either saturated or have one double bond and a chain of 16 to 22 carbon atoms, and in which the residues of the sialic acids derive from the group consisting of N-acetylneuramic acid and N-glycolylneuraminic acid and of their corresponding acids acylated at one of the hydroxy groups.
Claim 4
Dependent Claim
31 words
- A ganglioside as in claim 2, wherein the ceramide residue has sphingosine chains of 18 to 20 carbon atoms and acyl groups of 18 to 20 carbon atoms in length.
Claim 5
Dependent Claim
33 words
- A ganglioside derivative according to one of the previous claims, wherein the basic gangliosides are chosen from the group consisting of G M1 , G Dla' G Dlb and G T1b .
Claim 6
Dependent Claim
96 words
- A ganglioside derivative according to one of the previous claims, wherein the carboxylic esterifying groups derive from aliphatic alcohols with a maximum of 12 carbon atoms, or from araliphatic alcohols with only one benzene ring, optionally substituted with between 1 and 3 C 1-4 alkyl groups and a maximum of 4 carbon atoms in the aliphatic chain or with heterocyclic alcohols with a maximum of 12 carbon atoms and only one heterocyclic ring containing a hetero atom chosen from the group composed of N, S, and 0 or by C 1-14 alicyclic or aliphatic-alicyclic alcohols.
Claim 7
Dependent Claim
62 words
- A ganglioside derivative according to any one of claims 1-4, wherein the amide forming groups derive from aliphatic amines with a maximum of 12 carbon atoms and open or cyclic chains, from aralyphatic amines with only one benzene ring, optionally substituted by 1-3 C 1-4 alkyl groups and a maximum of 4 carbon atoms in the aliphatic part, or from ammonia.
Claim 8
Dependent Claim
64 words
- A gan g lioside derivative according to any one of the previous claims, wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues are peracylated with a C 1-10 aliphatic carboxylic acid or with an aromatic carboxylic acid selected from the group consisting of benzoic acid and its derivatives substituted with methyl, hydroxyl, amine or carboxyl groups.
Claim 9
Dependent Claim
56 words
- A ganglioside derivative according to claim 1, selected from the group consisting of the methyl, ethyl, propyl, isopropyl, N-butyl, isobutyl, tertiary butyl, undecyl, hydroxydecyl, heptyl, 2-methyl-?- pentyl, allyl, ethoxycarbonylmethyl, methoxyethyl, 1-methoxy-2-propyl. benzyl, phenethyl, cyclohexyl, menthyl, tetrahydrofurfuryl , tetrahydropyranyl and cyanotubutyryl esters of the gangliosides G M1 , G Dla' 4 Dlb and C Tlb .
Claim 10
Dependent Claim
56 words
- A ganglioside derivative according to claim 1, selected from the group consisting of the unsubstituted methylamide, ethylamide, propylamide, dimethylamide, diethylamide, butylamide, pyrrolidinamide, piperidinamide, 2-methylpiperidinamide, piperazinamide, 1-methylpipe- razinamide, morpholinamide, thiomorpholinamide, ethanolamide, benzylamide, ethylmethylamide, dimethylamino-propyl-1-amide, dimethylaminoethylamide, 6-hydroxyhexyl-l-amide, tetrahydrofurfurylamide, and phenyl- ethylamide of the g an g liosides G M1 , G D1b' GDla and G T1b .
Claim 11
Dependent Claim
28 words
- A ganglioside derivative according to claim 8 or 9, selected from the group consisting of the peracetylates, perpropionylates, perbutyrrylates, maleinylates, and succinylates or said esters or amides.
Claim 12
Dependent Claim
36 words
- A ganglioside derivative according to claim 1, selected from the group consisting of the peracetylates, perpriopionylates, perbutyrrylates, maleinylates and succinylates of the gangliosides G M1 , G D1b , G Dla and G T1b .
Claim 13
Dependent Claim
131 words
- A pharmaceutical composition comprising, as an active ingredient, an effective nerve pathology treatment amount of a ganglioside derivative of a ganglioside, said ganglioside being comprised of an oligosaccharide portion, at least one ceramide residue and at least one sialic acid residue, said ganglioside derivative being selected from the group consisting of an ester of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; an amide of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; and a peracylated derivative of said hydroxyl groups wherein said sialic acid residues have free carboxyl groups.
Claim 14
Dependent Claim
131 words
- A pharmaceutical composition comprising, as an active ingredient, an effective nerve pathology treatment amount of a ganglioside derivative of a ganglioside, said ganglioside being comprised of an oligosaccharide portion, at least one ceramide residue and at least one sialic acid residue, said ganglioside derivative being selected from the group consisting of an ester of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; an amide of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; and a peracylated derivative of said hydroxyl groups wherein said sialic acid residues have free carboxyl groups.
Claim 15
Dependent Claim
26 words
- A pharmaceutical composition comprising, as an active ingredient, an effective nerve pathology treatment amount of a ganglioside derivative according to any one of claims 1-11.
Claim 16
Dependent Claim
33 words
- A pharmaceutical composition as in claim 12, wherein the basic g a nglioside is selected from the group consisting of G M1 , G D1a , O D1b and G T1b .
Claim 17
Dependent Claim
132 words
- A method for the treatment of pathologies of the nervous System, comprising administering an effective amount of a ganglioside derivative ot a ganglioside, said ganglioside being comprised of an oligosaccharide portion, at least one ceramide residue and at least one sialic acid residue, said ganqlioside derivative being selected from the qroup consisting nf an ester of the carboxylic groups of said acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residue may optionally be peracylated; an amide of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; and a peracylated derivative of said hydroxyl groups wherein said sialic acid residues have free carboxyl groups.
Claim 18
Dependent Claim
132 words
- A method for the treatment of pathologies of the nervous System, comprising administering an effective amount of a ganglioside derivative ot a ganglioside, said ganglioside being comprised of an oligosaccharide portion, at least one ceramide residue and at least one sialic acid residue, said ganqlioside derivative being selected from the qroup consisting nf an ester of the carboxylic groups of said acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residue may optionally be peracylated; an amide of the carboxylic groups of said sialic acid residues wherein the hydroxyl groups of said oligosaccharide portion, said ceramide residue and said sialic acid residues may optionally be peracylated; and a peracylated derivative of said hydroxyl groups wherein said sialic acid residues have free carboxyl groups.
Claim 19
Dependent Claim
16 words
- A method as in claim 15, wherein said treatment is effective for stimulating nerve sprouting.
Claim 20
Dependent Claim
38 words
- A method according to claim 15, comprising administering, by oral route, from 0.05 to 5 mg per kg of body weight of a ganglioside derivative according to any one of claims 4, 8, 9, 10 and 11.
Claim 21
Dependent Claim
77 words
- A process for the preparation of a ganglioside derivative comprising: (a) treating, with an acid-type ion exchanger, a ganglioside, a mixture of gangliosides or a peracylated derivative thereof wherein the hydroxyl groups of said ganglioside are peracylated, to produce a metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof; (b) treating the thus produced metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof with a diazolalkane in a corresponding alcohol.
Claim 22
Dependent Claim
77 words
- A process for the preparation of a ganglioside derivative comprising: (a) treating, with an acid-type ion exchanger, a ganglioside, a mixture of gangliosides or a peracylated derivative thereof wherein the hydroxyl groups of said ganglioside are peracylated, to produce a metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof; (b) treating the thus produced metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof with a diazolalkane in a corresponding alcohol.
Claim 23
Dependent Claim
93 words
- A process for the preparation of a ganglioside derivative comprising: (a) treating, with an acid-type ion exchanger, a ganglioside, a mixture of gangliosides or a peracylated derivative thereof, wherein the hydroxyl groups of said ganglioside are peracylated, to produce a metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof; (b) treating the thus produced metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof with an etherifying agent containing a hydrocarbon to be ester bonded to the carboxylic groups of the sialic acid residues of said gangliosides.
Claim 24
Dependent Claim
93 words
- A process for the preparation of a ganglioside derivative comprising: (a) treating, with an acid-type ion exchanger, a ganglioside, a mixture of gangliosides or a peracylated derivative thereof, wherein the hydroxyl groups of said ganglioside are peracylated, to produce a metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof; (b) treating the thus produced metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof with an etherifying agent containing a hydrocarbon to be ester bonded to the carboxylic groups of the sialic acid residues of said gangliosides.
Claim 25
Dependent Claim
14 words
- A process according to claim 19, wherein said etherifying agent is hydrocarbon halogenide.
Claim 26
Dependent Claim
20 words
- A process according to any one of claims 18-20 wherein said metallic salt is a sodium or potassium salt.
Claim 27
Dependent Claim
41 words
- A process according to any one of claims 18-21 wherein said treatment of said metallic salt of said ganglioside, mixture of gangliosides or peracylated derivatives thereof is conducted in an aprotic solvent at a temperature of from 20 to 120°C.
Claim 28
Dependent Claim
14 words
- A process according to claim 22, wherein said solvent is dioxane or DMSO.
Claim 29
Dependent Claim
47 words
- A process for the preparation of a ganglioside derivative comprising treating an internal ester of a ganglioside or a mixture thereof with an alcohol to produce the corresponding ester in the carboxylic groups of the static acid residues of said ganglioside internal ester or mixture thereof.
Claim 30
Dependent Claim
47 words
- A process for the preparation of a ganglioside derivative comprising treating an internal ester of a ganglioside or a mixture thereof with an alcohol to produce the corresponding ester in the carboxylic groups of the static acid residues of said ganglioside internal ester or mixture thereof.
Claim 31
Dependent Claim
23 words
- A process according to claim 24, wherein said treatment is effected in the presence of a metallic alcoholate corresponding to said alcohol.
Claim 32
Dependent Claim
91 words
- A process according to claim 25, wherein said alcohol is an aliphatic alcohol with a maximum of 12 carbon atoms, or an araliphatic alcohol with only one benzene ring, optionally substituted with between 1 and 3 C 1-4 alkyl groups and a maximum of 4 carbon atoms in the aliphatic chain or a heterocyclic alcohol with a maximum of 12 carbon atoms and only one heterocyclic ring containing a hetero atom chosen from the group composed of N, S, and 0 or a C 1-14 aliphatic or aliphatic- alicyclic alcohol.
Claim 33
Dependent Claim
44 words
- A process according to claim 25, wherein said alcohol is a member selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tertiary butyl, undecyl, hydroxydecyl, heptyl, 2-methyl-1-pentyl, allyl, ethoxycarbonylmethyl, methoxyethyl, 1-methoxy-2-propyl, benzyl, phenethyl, cyclohexyl, menthyl, tetrahydrofurfuryl, tetrahydropyranyl and cyanobutyryl alcohols.
Claim 34
Dependent Claim
40 words
- A process according to claim 20, wherein the hydrocarbon group of said hydrocarbon halogenide is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tertiary butyl, undecyl, hydroxydecyl, heptyl, 2-methyl-1-pentyl, allyl, ethoxycarbonylmethyl, methoxyethyl, 1-methoxy-2-propyl, benzyl, phencthyl, cyclohexyl, menthyl, tetrahydrofurfuryl, tetrahydropyranyl or cyanobutyryl.
Claim 35
Dependent Claim
18 words
- A process according to claim 27, wherein the alcoholate is an alkaline metal alcoholate of said alcohol.
Claim 36
Dependent Claim
47 words
- A process for the preparation of a ganglioside derivative comprising treating a qanglioside or a mixture of gangliosides, a ganglioside internal ester or a mixture of ganglioside internal esters, or a carboxylic ester of a ganglioside or mixture of gangliosides with ammonia or with an amine.
Claim 37
Dependent Claim
47 words
- A process for the preparation of a ganglioside derivative comprising treating a qanglioside or a mixture of gangliosides, a ganglioside internal ester or a mixture of ganglioside internal esters, or a carboxylic ester of a ganglioside or mixture of gangliosides with ammonia or with an amine.
Claim 38
Dependent Claim
52 words
- A process according to claim 30, wherein said amine is aliphatic amine with a maximum of 12 carbon atoms and open or cyclic chains, an aralyphatic amine with only one benzene ring, optionally substituted by 1-3 C l-4 alkyl groups and a maximum of 4 carbon atoms in the aliphatic part.
Claim 39
Dependent Claim
41 words
- A process according to claim 31, wherein said amine is a member selected from the group consisting of methylamine, ethylamine, propylamine, isopropylamine, dimethylamine, diethylamine, butylamine, pyrrolidine, piperidine, 2-methyl-piperidine, piperazine, 1-methyl-piperazine, ethanolamine, benzylamine, ethylmethylamine, dimethylamino- propyl-I-amine, dimethylamino-ethylamine, 6-hydroxyhexyl-1-amine, tetrahydrofurfurylamine and 2-phenylethylamine.
Claim 40
Dependent Claim
36 words
- A process for the preparation of a ganglioside derivative comprising treating a ganglioside or a mixture of gangliosides, or an ester or amide derivative thereof, with an acylating agent in the presence of a base.
Claim 41
Dependent Claim
36 words
- A process for the preparation of a ganglioside derivative comprising treating a ganglioside or a mixture of gangliosides, or an ester or amide derivative thereof, with an acylating agent in the presence of a base.
Claim 42
Dependent Claim
42 words
- A process according to claim 33, wherein said acylating agent is a C 1-10 aliphatic carboxylic acid or an aromatic carboxylic acid selected from the group consisting of benzoic acid and its derivatives substituted with methyl, hydroxyl, amine or carboxy groups.
Claim 43
Dependent Claim
31 words
- A method according to claim 34, wherein said acylating agent is a member selected from the group consisting of acetic acid, propionic acid, butyric acid, maleic acid and succinic acid.
Claim 44
Dependent Claim
14 words
- A method according to claim 35, wherein said base is a tertiary amine.
Claim 45
Dependent Claim
21 words
- A method according to claim 33, wherein said acylating agent is an anhydride and said base is a tertiary amine.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.