Ethereal monosubstitutions of monosaccharide derivatives

Abstract

The invention provides a novel therapeutic composition comprising a pharmaceutically acceptable carrier containing a therapeutically effective amount of an ethereal monosubstitution of a monosaccharide derivative having the general formula S--O--Y, wherein S is the residue of the monosaccharide derivative selected from the group consisting of pentoses, hexoses and heptoses as single or polysubstituted acetals, ketals or esters and Y is selected from the group consisting of cyclic monovalent nitrogen-containing organic radicals and residua and monovalent organic radicals and residua having the general formula ##STR1## wherein R 1 is a divalent organic radical having a linear carbon chain length of about 1-7 carbon atoms and R 2 and R 3 are selected from the group consisting of --H, --OH, --SH, halogen and monovalent organic radicals and residua having a linear carbon chain length of about 1-7 carbon atoms. The invention also provides certain novel ethereal monosubstitutions of monosaccharide derivatives, of which 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidene-D-glucofuranose is an example. The novel monosaccharide derivatives show striking antiviral activity or other therapeutically valuable properties and are useful as active ingredients in the above therapeutic composition. The invention further provides a method of therapeutically treating warm-blooded animals with the aforementioned therapeutic composition and novel monosubstituted monosaccharide derivatives.

I claim: 
     
       1. A compound selected from the group consisting of 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylideneglucofuranose,   3-O-4'-(N'-methylpiperidyl)-1,2-O-isopropylidenglucosefuranose,   3-O-2'-(N',N'-dimethylaminoethyl)-1,2-O-isopropylideneglucofuranose,   3-O-3'-(2',N',N'-trimethylamino-n-propyl)-1,2-O-isopropylideneglucofuranose   3-O-2'-(N',N'-dimethylaminopropy)-1,2-O-isopropylideneglucosefuranose,   6-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidenegalactopyranose,   6-O-2'-(N',N'-dimethylaminopropyl)-1,2-O-isopropylidenegalactopyranose,   3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2:5,6-di-O-isopropylideneglucofuranose,   3-O-4'-(N'-methylpiperidyl)-1,2:5,6-di-O-isopropylideneglucofuranose,   3-O-2'-(N',N'-dimethylaminoethyl)-1,2:5,6-di-O-isopropylideneglucofuranose,   3-O-3'-(2',N',N'-trimethylamino-n-propyl)-1,2:5,6-di-O-isopropylideneglucofuranose,   3-O-2'-(N',N'-dimethylaminopropyl)-1,2:5,6-di-O-isopropyleneglucofuranose,   6-O-3'-(N',N'-dimethylamino-n-propyl)-1,2:3,4-di-O-isopropylidenegalactopyranose,   6-O-2'-(N',N'-dimethylaminopropyl)-1,2:3,4-di-O-isopropylidenegalactopyranose, α-N',N'-dimethylamino-iso-propyl-2,3:5,6-di-O-isopropylideneglucofuranoside, and therapeutically effective and acceptable organic and inorganic acid salts thereof.     
     
     
       2. A compound selected from the group consisting of 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidene-D-glucofuranose,   3-O-4-(N'-methylpiperidyl)-1,2-O-isopropylidene-D-glucofuranose,   3-O-2'-(N',N'-dimethylaminoethyl)-1,2-O-isopropylidene-D-glucofuranose,   3-O-3'-(2',N',N'-trimethylamino-n-propyl)-1,2-O-isopropylidene-D-glucofuranose,   3-O-2'-(N',N'-dimethylaminopropyl)-1,2-O-isopropylidene-D-glucofuranose,   6-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidene-D-galactopyranose,   6-O-2'-(N',N'-dimethylaminopropyl)-1,2-O-isopropylidene-D-galactopyranose,   3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose,   3-O-4'-(N'-methylpiperidyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose,   3-O-2'-(N',N'-dimethylaminoethyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose,   3-O-3'-(2',N',N'-trimethylamino-n-propyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose,   3-O-2'-(N',N'-dimethylaminopropyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose,   6-O-3'-(N',N'-dimethylamino-n-propyl)-1,2:3,4-di-O-isopropylidene-D-galactopyranose, p1 6-O-2'-(N',N'-dimethylaminopropyl)-1,2:3,4-di-O-isopropylidene-D-galactopyranose,   α-N',N'-dimethylamino-iso-propyl-2,3:5,6-di-O-isopropylidene-D-glucofuranoside, and therapeutically effective and acceptable organic and inorganic acid salts thereof.     
     
     
       3. A compound in accordance with claim 2 wherein the compound is 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidene-D-glucofuranose 
     
     
       4. A compound in accordance with claim 2 wherein the compound is 3-O-4'-(N'-methylpiperidyl)-1,2-O-isopropylidene-D-glucofuranose.   
     
     
       5. A compound in accordance with claim 2 wherein the compound is 3-O-2'-(N',N'-dimethylaminoethyl)-1,2-O-isopropylidene-D-glucofuranose.   
     
     
       6. A compound in accordance with claim 2 wherein the compound is 3-O-3'-(2',N',N'-trimethylamino-n-propyl)-1,2-O-isopropylidene-D-gulcofuranose.   
     
     
       7. A compound in accordance with claim 2 wherein the compound is 3-O-2'-(N',N'-dimethylaminopropyl)-1,2-O-isopropylidene-D-glucofuranose.   
     
     
       8. A compound in accordance with claim 2 wherein the compound is 6-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidene-D-galactopyranose.   
     
     
       9. A compound in accordance with claim 2 wherein the compound is 6-O-2'-(N',N'-dimethylaminopropyl)-1,2-O-isopropylidene-D-galactopyranose.   
     
     
       10. A compound in accordance with claim 2 wherein the compound is 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose.   
     
     
       11. A compound in accordance with claim 2 wherein the compound is 3-O-4'-(N'-methylpiperidyl)-1,2:5,6-di-O-isopropylidene-D-gulcofuranose.   
     
     
       12. A compound in accordance with claim 2 wherein the compound is 3-O-2'-(N',N'-dimethylaminoethyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose.   
     
     
       13. A compound in accordance with claim 2 wherein the compound is 3-O-3'-(2',N'N'-trimethylamino-n-propyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose.   
     
     
       14. A compound in accordance with claim 2 wherein the compound is 3-O-2'-(N',N'-dimethylaminopropyl)-1,2:5,6-di-O-isopropylidene-D-glucofuranose.   
     
     
       15. A compound in accordance with claim 2 wherein the compound is 6-O-3'-(N',N'-dimethylamino-n-propyl)-1,2:3,4-di-O-isopropylidene-D-galactopyranose.   
     
     
       16. A compound in accordance with claim 2 wherein the compound is 6-O-2'-(N',N'-dimethylaminopropyl)-1,2:3,4-di-O-iospropylidene-D-galactopyranose.   
     
     
       17. A compound in accordance with claim 2 wherein the compound is α-N',N'-dimethylamino-iso-propyl-2,3:5,6-O-isopropylidene-D-glucofuranoside.   
     
     
       18. A compound in accordance with claim 1 wherein the compound is in the form of a salt of an acid selected from the group consisting of HCl, HBr, H 2  SO 4 , HNO 3 , benzoic acid, p-aminobenzoic acid, p-acetamidobenzoic acid, p-hydroxybenzoic acid, alkane sulfonic acids, p-toluene sulfonic acid, lower alkyl monocarboxylic acids, oxalic acid, tartaric acid, lactic acid, pyruvic acid, malic acid, succinic acid, gluconic acid and glucuronic acid. 
     
     
       19. A compound in accordance with claim 18 wherein the said compound is 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylideneglucofuranose. 
     
     
       20. A compound in accordance with claim 19 wherein the said acid is HCl. 
     
     
       21. A compound in accordance with claim 2 wherein the compound is in the form of a salt of an acid selected from the group consisting of HCl, HBr, H 2  SO 4 , HNO 3 , benzoic acid, p-aminobenzoic acid, p-acetamidobenzoic acid, p-hydroxybenzoic acid, alkane sulfonic acids, p-toluene sulfonic acid, lower alkyl monocarboxylic acids, oxalic acid, tartaric acid, lactic acid, pyruvic acid, malic acid, succinic acid, gluconic acid and glucuronic acid. 
     
     
       22. A compound in accordance with claim 21 wherein the said compound is 3-O-3'-(N',N'-dimethylamino-n-propyl)-1,2-O-isopropylidene-D-glucofuranose. 
     
     
       23. A compound in accordance with claim 22 wherein the said acid is HCl. .Iadd. 24. A compound having the formula S--O--Y, and therapeutically effective and pharmaceutically acceptable organic acid and inorganic acid salts thereof, wherein S is the residue of a monosaccharide selected from the group consisting of pentoses, hexoses and heptoses which has been derivatized with at least one substance selected from the group consisting of (a) at least one aliphatic alcohol containing 1-18 carbon atoms to produce an ether group at the site of at least one available hydroxyl group, (b) at least one aldehyde containing 1-18 carbon atoms to produce at least one acetal group at the site of at least one available hydroxyl group, (c) at least one ketone containing 1-18 carbon atoms to produce at least one ketal group at the site of at least one available hydroxyl group, and (d) at least one organic acid residue containing 1-18 carbon atoms to produce an ester group at the site of at least one available hydroxyl group, and Y is selected from the group consisting of -(N',N'-dimethylamino-n-propyl), -N',N'-dimethylaminoisopropyl), -(N'-methylpiperidyl), -(N',N'-dimethylaminoethyl), -(2',N',N'-trimethylamino-n-propyl), -(N',N'-dimethylaminomethyl), -(N',N'-dimethylaminopropyl), -(N',N'-dimethylamino-iso-butyl), -(N',N' -dimethylamino-n-butyl), -(N',N'-dimethylamino-iso-pentyl), -(N',N'-dimethylaminopentyl), -(N'-methylamino-n-propyl), -(N'-methyl-N'-ethylamino-n-propyl), -(N',N'-diethylamino-n-propyl), -(N'-ethylamino-n-propyl), -(N'-propylamino-n-propyl), -(N',N'-iso-propylamino-n-propyl), -(1',2'-ethylimino-n-propyl), -(1"-n-propylpyrrolidyl), -(1"-n-propylpiperidyl), -piperidyl, -(N',N'-dimethylamino-sec-butyl), -(methylpiperidyl), -(methylpyrrolidyl) and -(N',N'-dimethylamino-1,2-propenyl). .Iaddend. .Iadd. 25. A compound according to claim 24 wherein the monosaccharide is a hexose. .Iaddend..Iadd. 26. A compound according to claim 25 wherein said hexose is glucose. .Iaddend..Iadd. 27. A compound according to claim 26 wherein said glucose is ethereally monosubstituted at the 1-O- or 6-O-position. .Iaddend..Iadd. 28. A compound according to claim 27 wherein said glucose is D-glucofuranose. .Iaddend..Iadd. 29. A compound according to claim 25 wherein said hexose is galactose. .Iaddend..Iadd. 30. A compound according to claim 29 wherein said galactose is substituted at the 6-O-position. .Iaddend..Iadd. 31. A compound according to claim 30 wherein said galactose is D-galactopyranose. .Iaddend.