Sulfated oligosaccharide derivatives

Abstract

The invention relates to novel compounds that have utility as inhibitors of heparan sulfate-binding proteins; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and/or antithrombotic treatment of a mammalian subject.

1 . A pharmaceutical or veterinary composition for the treatment of cancer in a mammalian subject, which composition comprises at least one compound of the general formula:
   [X] n —Y—ZR 1 R 2   I
   
       wherein:
 X and Y are each a monosaccharide unit wherein each hydroxyl group not involved in a glycosidic linkage is substituted independently by a group SO 3 M or H, where M is any pharmaceutically acceptable cation; 
 X and Y are any  D - or  L -hexose or pentose; 
 Y is in a cyclic or ring opened form; 
 Z is O, N, S or C or their higher oxidation states, or a bond, and is linked to the anomeric carbon when Y is a reducing monosaccharide; 
 R 1  is a linker selected from the group consisting of: alkyl, alkenyl, alkynyl, aryl, heteroalkyl, heteroaryl, acyl, aroyl, alkylamido, alkylthioamido, triazolyl, substituted triazolyl, and oxymethyl[1,2,3]-triazole-1-yl linker, or is a bond, wherein if R 1  is substituted triazolyl, the triazolyl is substituted by one or more of: halo, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, nitro, amino, C 1-6 alkylamino, C 1-6 dialkylamino, halomethyl, halomethoxy or acetyl; 
 R 2  is a lipophilic moiety selected from the group consisting of: cholesteryl, cholestanyl, cholate, deoxycholate, glycyrrhetinyl, C9 to C18 straight chain alkyl, substituted alkyl, C9 to C18 branched alkyl, alkylamido, substituted alkylamido, propylstearamide, straight chain acyl, branched acyl, and —C(O)-alkyl or —C(O)-aryl, in which the alkyl or aryl groups are optionally substituted by one or more of halo, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, nitro, amino, C 1-6 alkylamino, C 1-6 dialkylamino, halomethyl, halomethoxy or acetyl, wherein 
 if R 2  is substituted alkyl or substituted alkylamido, the group is substituted by one or more of: halo, hydroxy, C 1-6 alkoxy, nitro, amino, C 1-6 alkylamino, C 1-6 dialkylamino, halomethyl, halomethoxy or acetyl; 
 n is an integer from 0-6; and 
 the level of sulfation of each compound is between 70 and 100% of the total hydroxyl groups, wherein 
 when R 1  is a bond, then R 2  is not glycyrrhetinic acid or derivatives thereof; 
 when R 1  is a bond, and n=0 or 1, and Z is S, then R 2  is not a C18 straight chain alkyl group; 
 when n is 3-6, and R 1  is a bond, and X and Y are α(1→4)-linked glucose, then R 2  is not a C12 to C18 straight chain alkyl group; 
 when n is 3-5, and R 1  is a bond, and X and Y are β(1→3)-linked glucose, then R 2  is not a C9 to C12 straight chain alkyl group or cholesteryl group; 
 when n=0, Z═O, and R 1  is alkyl, then R 2  is not C9 to C18 straight chain alkyl; 
 when n=1, Z═O, and R 1  is alkyl, then R 2  is not alkylamido; 
 when n=0, Z═O, Y=glucopyranose and R 1  is a bond, then R 2  is not cholesteryl; and 
 when X and Y are ribose, and R 1  is a bond, then R 2  is not a C18 group; 
 
       together with a pharmaceutically or veterinarially acceptable carrier or diluent for at least one said compound. 
     
     
         2 . The pharmaceutical or veterinary composition according to  claim 1 , wherein in said at least one compound R 2  is cholestanyl. 
     
     
         3 . The pharmaceutical or veterinary composition according to  claim 1 , wherein in said at least one compound R 2  is propylstearamide. 
     
     
         4 . The pharmaceutical or veterinary composition according to  claim 1 , wherein said at least one compound is selected from the group consisting of:
 3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 65);   4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 70);   4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 76);   3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 87);   3-stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, decasodium salt (compound 123); and   3-stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, tridecasodium salt (compound 128).   
     
     
         5 . The pharmaceutical or veterinary composition according to  claim 1 , wherein in said at least one compound R 1  is a bond. 
     
     
         6 . The pharmaceutical or veterinary composition according to  claim 2 , wherein in said at least one compound R 1  is a bond. 
     
     
         7 . The pharmaceutical or veterinary composition according to  claim 6 , wherein in said at least one compound each X is a D-hexose, and Y is a D-hexose. 
     
     
         8 . The pharmaceutical or veterinary composition according to  claim 7 , wherein in said at least one compound n is 3. 
     
     
         9 . The pharmaceutical or veterinary composition of  claim 1 , wherein in said at least one compound:
 R 1  is a linker selected from the group consisting of: alkyl; alkenyl; alkynyl; aryl; heteroalkyl; heteroaryl; acyl; aroyl; alkylamido; alkylthioamido; triazolyl; and oxymethyl[1,2,3]-triazole-1-yl linker; or is a bond; and   R 2  is a lipophilic moiety selected from the group consisting of: cholesteryl; cholestanyl; cholate; deoxycholate; glycyrrhetinyl; C9 to C18 straight chain alkyl; alkylamido; propylstearamide; straight chain acyl; and branched acyl.   
     
     
         10 . A method for the treatment of cancer in a mammalian subject, which method comprises administering to the subject an effective amount of at least one compound of the general formula:
   [X] n —Y—ZR 1 R 2   I
   
       wherein:
 X and Y are each a monosaccharide unit wherein each hydroxyl group not involved in a glycosidic linkage is substituted independently by a group SO 3 M or H, where M is any pharmaceutically acceptable cation; 
 X and Y are any  D - or  L -hexose or pentose; 
 Y is in a cyclic or ring opened form; 
 Z is O, N, S or C or their higher oxidation states, or a bond, and is linked to the anomeric carbon when Y is a reducing monosaccharide; 
 R 1  is a linker selected from the group consisting of: alkyl, alkenyl, alkynyl, aryl, heteroalkyl, heteroaryl, acyl, aroyl, alkylamido, alkylthioamido, triazolyl, substituted triazolyl, and oxymethyl[1,2,3]-triazole-1-yl linker, or is a bond, wherein if R 1  is substituted triazolyl, the triazolyl is substituted by one or more of: halo, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, nitro, amino, C 1-6 alkylamino, C 1-6 dialkylamino, halomethyl, halomethoxy or acetyl; 
 R 2  is a lipophilic moiety selected from the group consisting of: cholesteryl, cholestanyl, cholate, deoxycholate, glycyrrhetinyl, C9 to C18 straight chain alkyl, substituted alkyl, branched alkyl, alkylamido, substituted alkylamido, propylstearamide, straight chain acyl, branched acyl, and —C(O)-alkyl or —C(O)-aryl, in which the alkyl or aryl groups are optionally substituted by one or more of halo, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, nitro, amino, C 1-6 alkylamino, C 1-6 dialkylamino, halomethyl, halomethoxy or acetyl, wherein 
 if R 2  is substituted alkyl or substituted alkylamido, the group is substituted by one or more of: halo, hydroxy, C 1-6 alkoxy, nitro, amino, C 1-6 alkylamino, C 1-6 dialkylamino, halomethyl, halomethoxy or acetyl; 
 n is an integer from 0-6; and 
 the level of sulfation of each compound is between 70 and 100% of the total hydroxyl groups, wherein 
 when R 1  is a bond, then R 2  is not glycyrrhetinic acid or derivatives thereof; 
 when R 1  is a bond, and n=0 or 1, and Z is S, then R 2  is not a C18 straight chain alkyl group; 
 when n is 3-6, and R 1  is a bond, and X and Y are α(1→4)-linked glucose, then R 2  is not a C12 to C18 straight chain alkyl group; 
 when n is 3-5, and R 1  is a bond, and X and Y are β(1→3)-linked glucose, then R 2  is not a C9 to C12 straight chain alkyl group or cholesteryl group; 
 when n=1, Z═O, and R 1  is alkyl, then R 2  is not alkylamido; and 
 when X and Y are ribose, and R 1  is a bond, then R 2  is not a C18 group; 
 
       or a composition comprising said at least one compound. 
     
     
         11 . The method according to  claim 10 , wherein in said at least one compound R 2  is cholestanyl. 
     
     
         12 . The method according to  claim 10 , wherein in said at least one compound R 2  is propylstearamide. 
     
     
         13 . The method according to  claim 10 , wherein said at least one compound is selected from the group consisting of:
 3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 65);   4-(cholestan-3-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 70);   4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 76);   3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 87);   3-stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, decasodium salt (compound 123); and   3-stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, tridecasodium salt (compound 128).   
     
     
         14 . The method according to  claim 10 , wherein in said at least one compound R 1  is a bond. 
     
     
         15 . The method according to  claim 11 , wherein in said at least one compound R 1  is a bond. 
     
     
         16 . The method according to  claim 15 , wherein in said at least one compound each X is a D-hexose, and Y is a D-hexose. 
     
     
         17 . The method according to  claim 16 , wherein in said at least one compound n is 3. 
     
     
         18 . The method according to  claim 10 , wherein in said at least one compound:
 R 1  is a linker selected from the group consisting of: alkyl; alkenyl; alkynyl; aryl; heteroalkyl; heteroaryl; acyl; aroyl; alkylamido; alkylthioamido; triazolyl; and oxymethyl[1,2,3]-triazole-1-yl linker; or is a bond; and   R 2  is a lipophilic moiety selected from the group consisting of: cholesteryl; cholestanyl; cholate; deoxycholate; glycyrrhetinyl; C9 to C18 straight chain alkyl; alkylamido; propylstearamide; straight chain acyl; and branched acyl.   
     
     
         19 . A pharmaceutical or veterinary composition for the treatment of cancer in a mammalian subject, which composition comprises at least one compound selected from the group consisting of:
 Dodecyl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 4);   12-(4-Phenyl-[1,2,3]triazol-1-yl)dodecyl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 8);   12-(4-Naphthalen-1-yl-[1,2,3]triazol-1-yl)dodecyl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 11);   3β-Cholesteryl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 17);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 20);   3-Stearamidopropyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 24);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 27);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 33);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1-2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 39);   3-Stearamidopropyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 44);   3-{4-(Cholestan-3β-yl-oxymethyl)-[1,2,3]triazol-1-yl}propyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 48);   3′-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 56);   3-{4-(Cholestan-3β-yl-oxymethyl)-[1,2,3]triazol-1-yl}propyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 60);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 65);   4-(Cholestan-3-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 70);   4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 76);   3β-Cholestanyl-2,3,4,6-tetra-O-sulfonato-α- D -mannopyranoside tetrasodium salt (compound 79);   N-(2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranosyl)-4-((3R,10S,12S,13R)-3-O-sodium sulfonato-12-O-acetyl-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide (compound 83);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 87);   4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sulfo-β- D -galactopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 93);   4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl 2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 97);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 102);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-β- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 107);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-β- D -galactopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 112);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranosyl-(1→6)-2,3,4-tri-O-sulfo-α- D -mannopyranoside, tridecasodium salt (compound 119);   3-Stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, decasodium salt (compound 123);   3-Stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, tridecasodium salt (compound 128);   2-(Cholestan-3-yloxy)acetamido-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, decasodium salt (compound 134);   1-[(Cholestan-3-yloxy)propyl]-3-[2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1-4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside]thiourea, decasodium salt (compound 139);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-((1-pyridinium-1-yl)-2,3,5,6-tetra-O-sulfo- D -glucoside, tridecasodium salt (compound 140); and   8-Pentadecanyl-2,3,4,6-tetra-O-sulfo- D -glucopyranoside, tetrasodium salt (compound 143);   together with a pharmaceutically or veterinarially acceptable carrier or diluent for at least one said compound.   
     
     
         20 . A method for the treatment of cancer in a mammalian subject, which method comprises administering to the subject an effective amount of at least one compound selected from the group consisting of:
 Dodecyl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 4);   12-(4-Phenyl-[1,2,3]triazol-1-yl)dodecyl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 8);   12-(4-Naphthalen-1-yl-[1,2,3]triazol-1-yl)dodecyl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 11);   3β-Cholesteryl 2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 17);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 20);   3-Stearamidopropyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 24);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 27);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 33);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1-2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 39);   3-Stearamidopropyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 44);   3-{4-(Cholestan-3β-yl-oxymethyl)-[1,2,3]triazol-1-yl}propyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→2)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 48);   3′-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 56);   3-{4-(Cholestan-3β-yl-oxymethyl)-[1,2,3]triazol-1-yl}propyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-2,4,6-tri-O-sodium sulfonato-α- D -mannopyranosyl-(1→3)-3,4,6-tri-O-sodium sulfonato-α- D -mannopyranoside (compound 60);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 65);   4-(Cholestan-3-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 70);   4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 76);   3β-Cholestanyl-2,3,4,6-tetra-O-sulfonato-α- D -mannopyranoside tetrasodium salt (compound 79);   N-(2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranosyl)-4-((3R,10S,12S,13R)-3-O-sodium sulfonato-12-O-acetyl-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide (compound 83);   3β-Cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β- D -glucopyranoside (compound 87);   4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sulfo-β- D -galactopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 93);   4-(Cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl 2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 97);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 102);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-β- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 107);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-β- D -galactopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, heptasodium salt (compound 112);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranosyl-(1→6)-2,3,4-tri-O-sulfo-α- D -mannopyranoside, tridecasodium salt (compound 119);   3-Stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, decasodium salt (compound 123);   3-Stearamidopropyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, tridecasodium salt (compound 128);   2-(Cholestan-3-yloxy)acetamido-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside, decasodium salt (compound 134);   1-[(Cholestan-3-yloxy)propyl]-3-[2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β- D -glucopyranoside]thiourea, decasodium salt (compound 139);   3′-Cholestanyl-2,3,4,6-tetra-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α- D -glucopyranosyl-(1→4)-((1-pyridinium-1-yl)-2,3,5,6-tetra-O-sulfo- D -glucoside, tridecasodium salt (compound 140); and   8-Pentadecanyl-2,3,4,6-tetra-O-sulfo- D -glucopyranoside, tetrasodium salt (compound 143);   or a composition comprising said at least one compound.