EPITOPE REDUCTION THERAPY

• US 20100022620A1
• Filed: 07/27/2007
• Published: 01/28/2010
• Est. Priority Date: 07/27/2006
• Status: Abandoned Application

• Current Assignee: Isis Innovation Limited
• Original Assignee: Isis Innovation Limited
• Inventors: Crispin, Matthew David Max, Platt, Frances Mary, Willison, Hugh John, Scanlan, Christopher
• Application Number:
  US12/375,068
• Publication Number:
  US 20100022620A1
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/431 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/6615 Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 31/7008 Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 31/7034 attached to a carbocyclic compound, e.g. phloridzin
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/708 : having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention provides the use of an inhibitor of glycolipid biosynthesis in the manufacture of a medicament for the treatment of a glycolipid-mediated autoimmune disease.

Claims

1-37. -37. (canceled)

38. A method of treating a glycolipid-mediated autoimmune disease, which method comprises administering to a patient in need of such treatment an effective amount of an inhibitor of glycolipid biosynthesis.

39. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is an inhibitor of a glycosyltransferase or a sulfotransferase.

40. A method according to claim 39 wherein the glycosyltransferase is a glucosyltransferase, sialyltransferase, galactosyltransferasae, ceramide galactosyltransferase, fucosyltransferase, or N-acetylhexosaminetransferase.

41. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is an inhibitor of glucosylceramide synthase.

42. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is an inhibitor of ceramide biosynthesis.

43. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is an inhibitor of serine palmitoyltransferase or an inhibitor of dihydroceramide synthase.

44. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is a compound of one of the following formulae (I), (II), (III), (IV), (V), (IX) and (XII):

wherein;

X is O S or NR⁵;

R⁵ is hydrogen, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkylene-aryl, substituted or unsubstituted C_1-20 alkylene-C_3-20 heteroaryl, substituted or unsubstituted C_1-20 alkylene-C_3-25 cycloalkyl, substituted or unsubstituted C_1-20 alkylene-C_3-20 heterocyclyl, substituted or unsubstituted C_1-20 alkylene-O—

C_3-20 heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted C_3-20 heteroaryl, substituted or unsubstituted C_3-25 cycloalkyl or substituted or unsubstituted C_3-20 heterocyclyl, or R⁵ forms, together with R¹, R¹¹, R⁴ or R¹⁴, a substituted or unsubstituted C_1-6 alkylene group, wherein said C_1-20 alkyl and C_1-20 alkylene are optionally interrupted by N(R′

), O, S or arylene wherein R′

is H, C_1-6 alkyl or aryl;

n is 0 or 1;

Y is O, S or CR⁶R¹⁶;

R¹, R¹¹, R⁴ and R¹⁴, which may be the same or different, are independently selected from hydrogen, hydroxyl, carboxyl, amino, thiol, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkoxy, substituted or unsubstituted aryloxy, acyl, ester, acyloxy, C_1-10 alkylamino, di(C_1-10)alkylamino, amido, acylamido, —

O—

C_3-25 cycloalkyl and —

O—

C_3-20 heterocyclyl, provided that one of R¹, R¹¹, R⁴ and R¹⁴ may form, together with R⁵, a substituted or unsubstituted C_1-6 alkylene group, wherein said C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R², R¹², R³, R¹³, R⁶ and R¹⁶, which may be the same or different, are independently selected from hydrogen, hydroxyl, carboxyl, amino, thiol, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkoxy, substituted or unsubstituted aryloxy, acyl, ester, acyloxy, C_1-10 alkylamino, di(C_1-10)alkylamino, amido, acylamido —

O—

CO_3-25 cycloalkyl and —

O—

C_3-20 heterocyclyl, wherein said C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R²¹ is selected from oxo, -L³⁰-R²³, -L³⁰-C(O)N(H)—

R²⁴ and a group of the following formula (VI);

L³⁰ is substituted or unsubstituted C_1-20 alkylene which is optionally interrupted by N(R′

), O, S or arylene;

R²³ is carboxyl, hydroxyl, ester, phosphonate ester, phosphate ester, phosphoric acid and phosphonic acid;

R²⁴ is C_1-20 alkyl which is unsubstituted or substituted with one or more groups selected from carboxyl, hydroxyl, ester, phosphonate ester, phosphate ester, phosphoric acid and phosphonic acid, wherein said C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R³⁰ is C_1-20 alkyl which is unsubstituted or substituted with one or more groups selected from carboxyl, hydroxyl, ester, amino, phosphonate ester, phosphate ester, phosphoric acid and phosphonic acid, wherein said C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene, and

R²² is hydroxyl, oxo, acyloxy, phosphoric acid or —

OC(O)-alk-C(O)OH, wherein alk is substituted or unsubstituted C_1-20 alkylene which is optionally interrupted by N(R′

), O, S or arylene;

Base is selected from a group of any one of the following formulae (a), (b), (c), (d), (e), (f) and (g);

y is 0 or 1;

R³¹ is OH;

R³² is H or OH;

or, provided that y is O, R³¹ and R³² together form —

O—

C(R³³)(R³⁴)—

O—

, wherein R³³ and R³⁴ are independently selected from H and methyl;

A is substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkylene-aryl, substituted or unsubstituted C_1-20 alkylene-C_3-20 heteroaryl, substituted or unsubstituted C_1-20 alkylene-C_3-25 cycloalkyl or substituted or unsubstituted C1120 alkylene-C_3-20 heterocyclyl, wherein said C_1-20 alkyl and C_1-20 alkylene are optionally interrupted by N(R′

), O, S or arylene, wherein R′

is H, C_1-6 alkyl or aryl, or A is a group of any one of the following formulae (g) to (k);

L⁷⁰, L⁷⁰¹ and L⁷⁰² are independently selected from —

O—

, —

C(R³⁵)(R³⁶)— and

—

NH—

, wherein R³⁵ and R³⁶ are independently selected from H, OH and CH₃;

R⁷⁰, R⁷¹ and R⁷⁰¹ are selected from OH, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkoxy, substituted or unsubstituted C_1-10 alkylamino and -L⁷¹-(X²)_m-L⁷²-R⁷²;

wherein m is 0 or 1;

X² is O, S, —

C(R⁴⁵)(R⁴⁶)—

or —

O—

C(R⁴⁵)(R⁴⁶)—

, wherein R⁴⁵ and R⁴⁶ are independently selected from H, OH, phosphonic acid or a phosphonic acid salt;

L⁷¹ and L⁷² are independently selected from a single bond and substituted or unsubstituted C_1-20 alkylene, which C_1-20 alkylene is optionally interrupted by N(R′

), O, S or arylene, wherein R′

is H, C_1-6 alkyl or aryl; and

R⁷² is CO_3-25 cycloalkyl or C_3-20 heterocyclyl;

L^J is substituted or unsubstituted C_1-20 alkylene;

R^J1, R^J2, R^J3, R^J4, R^J5, R^J6 and R^J7, which are the same or different, are independently selected from hydrogen, hydroxyl, carboxyl, amino, thiol, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkoxy, substituted or unsubstituted aryloxy, acyl, ester, acyloxy, C_1-10 alkylamino, di(C_1-10)alkylamino, amido, acylamido, —

N(H)C(O)CH═

CH—

R^J8, —

C_3-25 cycloalkyl and —

O—

C_3-20 heterocyclyl, wherein said C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene, and wherein R^J8 is substituted or unsubstituted C_1-20 alkyl;

L^K1 and L^K2, which are the same or different, are independently selected from a single bond and substituted or unsubstituted C_1-20 alkylene;

X^K is N or C(R^K6), wherein R^K6 is H, COOH or ester;

Z^K is O or CH(R^K5);

p is 0 or 1;

R^K1, R^K2, R^K3, R^K4 and R^K5, which are the same or different, are independently selected from hydrogen, hydroxyl, carboxyl, amino, thiol, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkoxy, substituted or unsubstituted aryloxy, acyl, ester, acyloxy, C_1-10 alkylamino, di(C_1-10)alkylamino, amido, acylamido, —

O—

C_3-25 cycloalkyl and —

O—

C_3-20 heterocyclyl, wherein said C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R^IVa and R^IVd, which are the same or different, are independently selected from H,

substituted or unsubstituted C_1-6 alkyl or substituted or unsubstituted phenyl;

R^IVb is H, substituted or unsubstituted aryl, —

CH═

CHR^IVf, or substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene wherein R′

is H, C_1-6 alkyl or aryl;

R^IVc is H, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted phenyl or —

C(O)R^IVg;

R^IVf is H or substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R^IVg is H or substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R^IVe is H, hydroxyl, carboxyl, amino, thiol, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkoxy, substituted or unsubstituted aryloxy, acyl, ester, acyloxy, C_1-10 alkylamino, di(C_1-10)alkylamino, amido, acylamido, —

O—

C_3-25 cycloalkyl, —

O—

C_3-20 heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted C_3-20 heteroaryl, substituted or unsubstituted C_3-25 cycloalkyl or substituted or unsubstituted C_3-20 heterocyclyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

L^IV is substituted or unsubstituted C_1-20 alkylene which C_1-20 alkylene is optionally interrupted by N(R′

), O, S or arylene;

R⁹¹ and R⁹² which are the same or different, are independently selected from H, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted aryl and -L⁹¹-R⁹⁵, wherein L⁹¹ is substituted or unsubstituted C_1-20 alkylene, wherein said C_1-20 alkyl and said C_1-20 alkylene are optionally interrupted by N(R′

), O, S or arylene wherein R′

is H, C_1-6 alkyl or aryl, and wherein R⁹⁵ is substituted or unsubstituted aryl, amino, C_1-10 alkylamino or di(C_1-10)alkylamino;

R⁹³ is -L⁹²-R⁹⁶, wherein L⁹² is a single bond or substituted or unsubstituted C_1-20 alkylene, which C_1-20 alkylene is optionally interrupted by N(R′

), O, S or arylene, and wherein R⁹⁶ is amido or substituted or unsubstituted aryl;

R⁹⁴ is H or substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

q is 0 or 1;

r is 0 or 1;

R^IXa is H, COOH or an unsubstituted or substituted ester;

R^IXb is an unsubstituted or substituted C_1-6 alkyl;

R^IXc and R^IXd, which are the same or different, are each independently selected from H, unsubstituted or substituted C_1-6 alkyl and unsubstituted or substituted phenyl;

R^IXe and R^IXf, which are the same or different, are each independently selected from H, unsubstituted or substituted C_1-6 alkyl, unsubstituted or substituted phenyl and unsubstituted or substituted acyl;

either (a) one of R^IXg and R^IXh is H and the other is OR^Ixr, wherein R^IXr is selected from H, unsubstituted or substituted C_1-6 alkyl, unsubstituted or substituted phenyl and unsubstituted or substituted acyl, or (b) R^IXg and R^IXh together form an oxo group;

R^IXi is H, unsubstituted or substituted C_1-6 alkyl, unsubstituted or substituted C_1-6 alkoxy and unsubstituted or substituted phenyl;

R^IXj is H, unsubstituted or substituted C_1-6 alkyl or a group of the following formula (X);

in which R^IXn and R^IXo, which are the same or different, are each independently selected from OH, unsubstituted or substituted C_1-6 alkoxy, unsubstituted or substituted phenoxy, amino, unsubstituted or substituted C_1-6 alkylamino and unsubstituted or substituted di(C_1-6)alkylamino;

R^IXk is H, unsubstituted or substituted C_1-6 alkyl or a group of the following formula (XI);

in which R^IXp and R^IXq, which are the same or different, are each independently selected from OH, unsubstituted or substituted C_1-6 alkoxy, unsubstituted or substituted phenoxy, amino, unsubstituted or substituted C_1-6 alkylamino and unsubstituted or substituted di(C_1-6)alkylamino;

R^IXm is selected from H and unsubstituted or substituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or phenylene, wherein R′

is H, C_1-6 alkyl or phenyl;

R^Xa is H, substituted or unsubstituted C_1-20 alkyl, substituted or unsubstituted C_1-20 alkylene-aryl, substituted or unsubstituted C_1-20 alkylene-C_3-20 heteroaryl, substituted or unsubstituted C_1-20 alkylene-C_3-25 cycloalkyl, substituted or unsubstituted C_1-20 alkylene-C_3-20 heterocyclyl, substituted or unsubstituted C_1-20 alkylene-O—

C_3-20 heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted C_3-20 heteroaryl, substituted or unsubstituted C_3-25 cycloalkyl or substituted or unsubstituted C_3-20 heterocyclyl wherein said C_1-20 alkyl and C_1-20 alkylene are optionally interrupted by N(R′

), O, S or arylene wherein R′

is H, C_1-6 alkyl or aryl; and

R^Xb and R^Xc, which are the same or different, are independently selected from H, unsubstituted or substituted C_1-10 alkyl and unsubstituted or substituted aryl;

or a pharmaceutically acceptable salt thereof.

45. A method according to claim 44 wherein the compound has the following formula (Ia):

wherein Y is O, S or CHR⁶; and

X, n, R¹, R², R³, R⁴, R⁵, R⁶ and R¹¹ are as defined in claim 7.

46. A method according to claim 45 wherein X is NR⁵;

n is 1;

Y is CHR⁶;

R¹¹ is H; and

R⁵ is selected from;

hydrogen;

unsubstituted or substituted C_1-20 alkyl which is optionally interrupted by O; and

—

C_1-4 alkylene-O—

C_3-20 heterocyclyl, wherein said C_1-4 alkylene is unsubstituted and said C_3-20 heterocyclyl is a group of the following formula (m);

in which each R^m is independently selected from C_1-6 alkyl, OH, acyloxy, SH, C_1-6 alkoxy, aryloxy, amino, C_1-10 alkylamino, di(C_1-10)alkylamino, amido and acylamido;

or R⁵ forms, together with R⁴, a substituted or unsubstituted C_1-6 alkylene group.

47. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is selected from N-butyldeoxynojirimycin;

N-nonyldeoxynojirimycin;

N-butyldeoxygalactonojirimycin;

N-5-adamantane-1-yl-methoxypentyl-deoxynojirimycin;

alpha-homogalactonojirimycin;

nojirimycin;

deoxynojirinycin;

N7-oxadecyl-deoxynojirimycin;

deoxygalactonojirimycin;

N-butyl-deoxygalactonojirimycin;

N-nonyl-deoxygalactonojirimycin;

N-nonyl-6deoxygalactonojirimycin;

N7-oxanonyl-6deoxy-DGJ;

alpha-homoallonojirimycin;

beta-1-C-butyl-deoxygalactonojirimycin;

1,5-dideoxy-1,5-imino-D-glucitol, 1,5-(Butylimino)-1,5-dideoxy-D-glucitol;

1,5-(Methylimino)-1,5-dideoxy-D-glucitol;

1,5-(Hexylimino)-1,5-dideoxy-D-glucitol;

1,5-(Nonylylimino)-1,5-dideoxy-D-glucitol;

1,5-(2-Ethylbutylimino)-1,5-dideoxy-D-glucitol;

1,5-(2-Methylpentylimino)-1,5-dideoxy-D-glucitol;

1,5-(Benzyloxycarbonylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Phenylacetylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Benzoylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Ethyl malonylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Hexylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Nonylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Benzyloxycarbonylimino)-1,5-dideoxy-D-glucitol, tetraisobutyrate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, tetrabutyrate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, tetrapropionate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, tetrabenzoate;

1,5-Dideoxy-1,5-imino-D-glucitol, tetraisobutyrate;

1,5-(Hydrocinnamoylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Methyl malonylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, tetraisobutyrate;

1,5-(Butylimino)-1,5-dideoxy-4R,6-O-(phenylmethylene)-D-glucitol, diacetate;

1,5-[(Phenoxymethyl)carbonylimino]-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-[(Ethylbutyl)imino]-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, 2,3-diacetate;

1,5-(Hexylimino)-1,5-dideoxy-4R,6-O-(phenylmethylene)-D-glucitol, diacetate;

1,5-(Hexylimino)-1,5-dideoxy-D-glucitol, 2,3-diacetate;

1,5-[(2-Methylpentyl)imino]-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, 6-acetate;

1,5-[(3-Nicotinoyl)imino]-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Cinnamoylimino)-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Butylimino)-1,5-dideoxy-D-glucitol, 2,3-dibutyrate;

1,5-(Butylimino)-1,5-dideoxy-4R,6-O-(phenylmethylene)-g-glucitol, 2,3-dibutyrate;

1,5-(Phenylacetylimino)-1,5-dideoxy-D-glucitol, tetraisobutyrate;

1,5-[(4-Chlorophenyl)acetylimino]-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-[(4-Biphenyl)acetylimino]-1,5-dideoxy-D-glucitol, tetraacetate;

1,5-(Benzyloxycarbonylimino)-1,5-dideoxy-D-glucitol, tetrabutyrate;

1,5-Dideoxy-1,5-imino-D-glucitol, tetrabutyrate;

3,4,5-piperidinetriol, 1-propyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-pentyl-2-(hydroxymethyl)-, (2S,3R,4R,55);

3,4,5-piperidinetriol, 1-heptyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-butyl-2-(hydroxymethyl)-, (2S,3S,4R, SS);

3,4,5-piperidinetriol, 1-nonyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-(1-ethyl)propyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-(3-methyl)butyl-2-(hydroxymethyl)-, (2S,3R,4R,5S), 3,4,5-piperidinetriol, 1-(2-phenyl)ethyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-(3-phenyl)propyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-(1-ethyl)hexyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-(2-ethyl)butyl-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-[(2R)-(2-methyl-2-phenyl)ethyl]-2-(hydroxymethyl)-, (2S,3R,4R,5S);

3,4,5-piperidinetriol, 1-[(2S-(2-methyl-2-phenyl)ethyl]-2-(hydroxymethyl)-, (2S,3R,4R,5S), β

-L-homofuconojirimycin;

propyl 2-acetamido-2-deoxy-4-O-(β

-D-galactopyranosyl)-3-O-(2-(N-(β

-L-homofuconojirimycinyl))ethyl)-α

-D-glucopyranoside;

ido-N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin;

N-(adamantane-1-yl-methoxypentyl)-L-ido-deoxynojirimycin;

N-(adamantane-1-yl-methoxypentyl)-D-galacto-deoxynojirimycin;

C1-beta-(adamantane-1-yl-methoxypentyl)-deoxynojirimycin;

N-methyl-C1-beta-(adamantane-1-yl-methoxypentyl)-deoxynojirimycin;

N-butyl-C1-beta-(adamantane-1-yl-methoxypentyl)-deoxynojirimycin;

2-O-(adamantane-1-yl-methoxypentyl)-deoxynojirimycin;

N-methyl-2-O-(adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin;

N-butyl-2-O-(adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin;

N-benzyloxycarbonyl-2-O-(adamantane-1-yl-methoxypentyl)-3,4,6-tri-O-benzyl-deoxy-nojirimycin; and

N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin.

48. A method according to claim 45 wherein:

X is NR⁵;

Y is O or S;

n is either 0 or 1;

R¹¹ is H; and

R⁵ is selected from hydrogen and a group of the following formula (VIII);

in which;

R⁴⁰ and R⁴², which are the same or different, are independently selected from H, substituted or unsubstituted C_1-6 alkyl or substituted or unsubstituted phenyl;

R⁴¹ is H, substituted or unsubstituted aryl, —

CH═

CHR⁴⁴, or substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene wherein R′

is H, C_1-6 alkyl or aryl;

R⁴³ is H, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted phenyl or —

C(O)R⁴⁷;

R⁴⁴ is H or substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene;

R⁴⁷ is substituted or unsubstituted C_1-20 alkyl, which C_1-20 alkyl is optionally interrupted by N(R′

), O, S or arylene; and

L⁴⁰ is substituted or unsubstituted C_1-10 alkylene.

49. A method according to claim 45 wherein the inhibitor of glycolipid biosynthesis is selected from:

D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol;

D,L-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol;

D-threo-1-phenyl-2-palmitoilamino-3-pyrrolidino-1-propanol;

4′

-hydroxy-D-threo-1-phenyl-2-palmitoilamino-3-pyrrolidino-1-propanol;

3′

,4′

-ethylenedioxy-P4 and 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine.

50. A method according to claim 45 wherein:

X is O or S;

n is 1;

Y is CHR⁶;

R¹¹ is H;

R⁶ is H, hydroxyl, acyloxy, C_1-20 alkoxy, C_1-10 alkylamino or di(C_1-10)alkylamino;

R² and R³, which may be the same or different, are independently selected from H, hydroxyl, C_1-20 alkoxy, acyloxy or acylamido;

R⁴ is H, hydroxyl, acyloxy, thiol or C_1-20 alkyl, which C_1-20 alkyl is unsubstituted or substituted with one, two, three or four groups selected from hydroxyl, acyloxy and thiol and

R¹ is C_1-20 alkoxy, aryloxy or —

O—

C_3-20 heterocyclyl.

51. A method according to claim 45 wherein the inhibitor of glycolipid biosynthesis is selected from:

52. A method according to claim 45 wherein:

X is or S;

n is 1;

Y is CHR⁶;

R⁶ is H, hydroxyl, acyloxy or C_1-20 alkoxy;

R¹ and R¹¹ which may be the same or different, are independently selected from H, C_1-20 alkyl, hydroxyl, acyloxy, C_1-20alkoxy, carboxyl, ester, —

O—

CO_3-25 cycloalkyl, and a group of the following formula (VII);

wherein L⁶⁰ is substituted or unsubstituted C_1-20 alkylene;

x is 0 or 1;

y is 0 or 1;

A is CHR′

″ and

R is H, C_1-20 alkyl, C_3-20 heterocyclyl, C_3-25 cycloalkyl, aryl or C_1-20 alkoxy, wherein R′

″

is hydroxyl, C_1-6 alkoxy, aryloxy or acyl;

R² is H, C_1-20 alkyl, hydroxyl, acyloxy or —

O—

C_3-20 heterocyclyl;

R³ is H, hydroxyl, acyloxy, C_1-20 alkoxy or acylamido; and

R⁴ is H, carboxyl, ester or C_1-20 alkyl which is unsubstituted or substituted with one, two, three or four groups selected from hydroxyl and thiol.

53. A method according to claim 45 wherein the inhibitor of glycolipid biosynthesis is cytidin-5′

-yl sialylethylphosphonate, sialic acid or Soyasaponin I.

54. A method according to claim 44 wherein the compound is of formula (II), and wherein:

R²¹ is selected from oxo, -L³⁰-R²³, -L³⁰-C(O)N(H)—

R²⁴ and a group of the following formula (VI);

wherein

L³⁰ is substituted or unsubstituted C_1-6 alkylene,

R²³ is hydroxyl, carboxyl, ester or phosphate ester,

R²⁴ is C_1-6 alkyl which is unsubstituted or substituted with one or two carboxyl groups;

R³⁰ is C_1-6 alkyl which is unsubstituted or substituted with one or two groups selected from hydroxyl, carboxyl, amino and phosphonate ester; and

R²² is as defined in claim 7.

55. A method according to claim 44 wherein R²¹ is a group selected from oxo and the groups having the following structures:

56. A method according to claim 44 wherein R²² is selected from hydroxyl, oxo, phosphoric acid, —

OC(O)—

CH₂—

CH₂—

C(O)OH and —

OC(O)—

CH(NH₂)—

CH₂—

C(O)OH.

57. A method according to claim 44 wherein the inhibitor of glycolipid biosynthesis is selected from the compounds of formula (II) listed in Table 1.

58. A method according to claim 44 wherein the compound is of formula (III) and wherein:

Base is selected from (a), (b), (c), (d) and (e);

y is 0 and R³¹ and R³² are both —

OH;

A is either (g), (h) or (i);

L⁷⁰, L⁷⁰¹ and L⁷⁰² are selected from O, CH₂, CHOH, C(OH)(CH₃) and NH; and

R⁷⁰, R⁷¹ and R⁷⁰¹ are as defined in claim 7.

59. A method according to claim 44 wherein the inhibitor of glycolipid biosynthesis is selected from the compounds of formula (II) listed in Table 2.

60. A method according to claim 44 wherein the compound is of formula (IV) and wherein:

R^IVa and R^IVd are both H;

R^IVc is —

C(O)R^IVg;

R^IVg is unsubstituted C_1-20 alkyl;

R^IVb is —

CH═

CHR^IVf, wherein R^IVf is unsubstituted C_1-20 alkyl, or R^IVb is a group of the following formula (IVa);

in which R^IVh is H, C_1-6 alkyl or phenyl, or R^IVh forms, together with R^IVi, a bidentate group of the structure —

O-alk-O—

; and

R^IVi is H, CO_1-6 alkyl or phenyl, or R^IVi forms, together with R^IVh, a bidentate group of the structure —

O-alk-O—

, wherein alk is substituted or unsubstituted C_1-6 alkylene; and

R^IVe is OH, substituted or unsubstituted aryl, substituted or unsubstituted C_3-20 heteroaryl, substituted or unsubstituted C_3-25 cycloalkyl or substituted or unsubstituted C_3-20 heterocyclyl.

61. A method according to claim 44 wherein the compound is of formula (V) and wherein

R⁹¹ is H, —

C_1-4 alkylene-amino, —

C_1-4 alkylene-C_1-10 alkylamino or —

C_1-4 alkylene-di(C_1-10)alkylamino;

R⁹² is —

C_1-4 alkylene-phenyl, wherein said phenyl is substituted or unsubstituted;

R⁹³ is -L⁹²-R⁹⁶, wherein L⁹² is unsubstituted C_1-10 alkylene and R⁹⁶ is amido or substituted or unsubstituted phenyl; and

R⁹⁴ is C_1-10 alkyl, which C_1-10 alkyl is unsubstituted or substituted with a hydroxyl group.

62. A method according to claim 44 wherein the inhibitor of glycolipid biosynthesis is selected from the compounds of formula (V) listed in Table 3.

63. A method according to claim 44 wherein the compound is of formula (IX) and wherein r is 0;

q is 1;

R^IXa is H;

R^IXb is unsubstituted C_1-6 alkyl;

R^IXc and R^IXd are independently selected from H and unsubstituted C_1-6 alkyl;

R^IXe and R^IXf are independently selected from H and unsubstituted C_1-6 alkyl;

one of R^IXg and R^IXh is H and the other is OR^IXr, wherein R^IXr is selected from H and unsubstituted C_1-6 alkyl;

R^IXi is unsubstituted C_1-6 alkyl;

R^IXj is a group of formula (X);

R^IXk is a group of formula (XI);

R^IXn, R^IXo, R^IXp and R^IXq, which are the same or different, are independently selected from H and unsubstituted C_1-6 alkyl; and

R^IXm is unsubstituted or substituted C_1-10 alkyl.

64. A method according to claim 44 wherein the compound is of formula (IX) and wherein r is 1, q is 0;

R^IXa is COOH or an unsubstituted ester;

R^IXb is C_1-6 alkyl substituted with a hydroxyl group;

R^IXc, R^IXd, R^IXe, R^IXf, R^IXj and R^IXk which may be the same or different, are independently selected from H and unsubstituted C_1-6 alkyl;

R^IXg and R^IXh together form an oxo group;

R^IXi is H; and

R^IXm is unsubstituted or substituted C_1-6 alkyl.

65. A method according to claim 44 wherein the compound is of formula (XII) and wherein R^Xa, R^Xb and R^Xc, which are the same or different, are independently selected from H, unsubstituted C_1-6 alkyl and unsubstituted phenyl.

66. A method according to claim 44 wherein the inhibitor of glycolipid biosynthesis is:

a compound of formula (IX), which compound is either Fumonisin or Myriocin;

or a compound of formula (XII), which compound is L-cycloserine.

67. A method according to claim 38 wherein the inhibitor of glycolipid biosynthesis is RNA.

68. A method according to claim 66 wherein the RNA is antisense RNA or siRNA.

69. A method according to claim 38 wherein the glycolipid-mediated autoimmune disease is an autoimmune peripheral neuropathy;

an autoimmune central neuropathy;

a connective tissue disease;

an autoimmune complication of a drug therapy;

an autoimmune complication of a vaccine;

a psycho-neuro-endocrinological autoimmune disease;

an autoimmune vasculitide;

an autoimmune thyroiditis;

a non-vascular dementia;

an autoimmune endocrinopathy;

a late complication of an infective tick borne disease;

an autoimmune arthritis;

an autoimmune gastrointestinal disease;

an autoimmune clotting disorder;

a glomerulonephritides;

autoimmune hemolytic anemia;

autoimmune hepatitis;

an ear disorder;

or an autoimmune inner ear disease.

70. A method according to claim 38 wherein the glycolipid-mediated autoimmune disease is Guillain-Barré

syndrome;

a variant of Guillain-Barré

syndrome;

Guillain-Barré

syndrome with opthalmoplegia;

Miller Fisher syndrome;

Acute motor axonal neuropathy;

Motor neuropathy;

Motor neuropathy with multifocal conduction blocks;

Lower motor neuron syndromes;

Chronic inflammatory demyelinating polyneuropathy;

Multifocal chronic inflammatory demyelinating polyneuropathy;

Acute inflammatory demyelinating polyneuropathy;

Subacute inflammatory demyelinating polyneuropathy;

Sensory neuropathies;

Multifocal Motor Neuropathy;

Multifocal motor sensory neuropathy;

Acute Motor Sensory Axonal neuropathy;

Multifocal motor demyelinating neuropathy;

Chronic idiopainic sensory ataxic neuropathy;

Chronic recurrent polyneuropathy;

Mixed motor sensory neuropathy;

Sciatica;

Autoimmune mononeuritis multiplex;

Acute relapsing sensory-dominant polyneuropathy associated with anti-GQ1b antibody;

Amyotrophic lateral sclerosis;

Diabetic neuropathy;

Acute panautonomic neuropathy;

Bell'"'"'s palsy;

Acute opthalmoparesis;

Multiple sclerosis;

Transverse myelitis;

Optic neuritis;

Chronic myelinic neuropathy with IgM gammopathy;

Cryptogenic partial epilepsies;

Partial oculomotor nerve palsy;

Isolated cranial neuropathy;

Autoimmune cerebellar disease;

Acute Disseminated Encephalomyelitis;

Stiff-man syndrome;

Bickerstaff'"'"'s brainstem encephalopathy;

Systemic lupus erythamatosus;

Discoid lupus;

Scleroderma;

Morphoea;

CREST;

Mixed connective tissue disease;

Relapsing polychondritis;

Sjogren'"'"'s syndrome;

Primary fibromyalgia syndrome;

an autoimmune complication of drug therapy with Tumor necrosis factor-□

blocker, Interferon-□

Tacrolimus (FK506), Cyclosporine A, Suramin, Zimeldine, Cisplatin, Captopril, Danazol, Gold, Penicillamine, Streptokinase or Anistreplase;

an autoimmune complication of vaccination with Influenza Vaccination;

an autoimmune complication of vaccination with Menactra meningococcal conjugate vaccine;

Fibromyalgia syndrome;

Chronic fatigue syndrome;

Behç

et'"'"'s disease;

Hashimoto'"'"'s thyroiditis;

Graves'"'"' disease;

Alzheimer'"'"'s disease;

Insulin-dependent (type I) diabetes mellitus;

Neuroborreliosis;

Acute Disseminated Encephalomyelitis;

Guillain-Barré

disease;

Rheumatoid arthritis;

Still'"'"'s disease;

Coeliac disease;

Crohn'"'"'s disease;

Ulcerative colitis;

Primary adrenal failure;

Pernicious anoemia;

Idiopathic thrombocytopenic purpura;

IgA Nephropathy;

Meniere'"'"'s disease;

Autoimmune hemolytic anemia;

Autoimmune hepatitis;

Autoimmune inner ear disease or Acute opthalmoparesis.