Patent EA-004705-B1 (EA)
Title: Use of n-substituted 1,5-dideoxy-1,5-imino-d-glucitol compounds for treating infections caused by hepatitis virus
Inventor: MUELLER RICHARD A
IPC: A61K31/445
Filed: 1999-02-12
Abstract: 1. A method for treating a hepatitis virus infection in a mammal, comprising administering to said mammal an anti-hepatitis virus composition, characterized in that said composition comprises only glucamine compound or a pharmaceutically acceptable salt thereof effective to hepatitis virus amount and comprising at least one N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound of Formula I or a pharmaceutically acceptable salt thereof: wherein: R is selected from the group consisting of straight chain alkyl having a chain length of C7-to C20, branched chain alkyl having a chain length of C3 to C20, in the main chain, alkoxyalkyl, arylalkyl with said number of carbon atoms in alkyl moiety for alkoxyalkyl, and for arylalkyl with said number of carbon atoms in aryl moiety is from C6 to C18, and the alkyl moiety having a chain length from C1 to C20, cycloalkyl comprising from C3 to C20, wherein W, X, Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl having a chain length of C1 to C20, aroyl the aryl moiety of which is from C6 to C18 and trifluoroalkanoyl. 2. The method of claim 1, wherein R is straight chain alkyl having a chain length of C7 to C20 and W, X, Y and Z are each hydrogen. 3. The method of claim 2, wherein R is nonyl. 4. The method of claim 1, wherein R is straight chain alkyl having a chain length of C7 to C20 and W, X, Y, and Z are each alkanoyl. 5. The method of claim 4, wherein R is nonyl. 6. The method of claim 5, wherein said alkanoyl is butanoyl. 7. The method of claim 1, wherein said one N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound is selected from the group consisting of: N-(n-heptyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-octyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-undecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-dodecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-tridecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-tetradecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-pentadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-hexadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-heptadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-octadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-nonadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-eicosyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-heptyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-octyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-undecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-dodecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-tridecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-tetradecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-pentadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-hexadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-heptadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-octadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-nonadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-eicosyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(2-ethylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(4-ethylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(5-methylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(3-propylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(1-pentyl pentylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(1-butylbutylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(7-methlyloctyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(8methylonyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(9-methyldecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(10-methylundecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(6-cyclohexylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(4-cyclohexylbutyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(2-cyclohexylethyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(1-cyclohexylmethyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(1-phenylmethyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(3-phenylpropyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(3-(4-methyl)phenylpropyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(6-phenylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(7-oxa-n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(7-oxa-n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(7-oxa-n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(3-oxa-n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(9-oxa-n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(7-oxa-n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(3-oxa-n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(3-oxa-n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol; and N-(7,10,13-trioxa-n-tetradecyl)-1,5-dideoxy-1,5-imino-D-glucitol. 8. The method of claim 1, wherein said pharmaceutically acceptable salt is selected from the group consisting of acetate, adipate, alginate, citrate, phosphate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, mesylate, and undecanoate. 9. A method for treating a hepatitis virus infection in a mammal, comprising administering to said mammal an anti-hepatitis virus composition, comprising effective amount to hepatitis virus and at least one N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound of Formula I or a pharmaceutically acceptable salt thereof: wherein: R is selected from the group consisting of straight chain alkyl having a chain length of C7-to C20, branched chain alkyl having a chain length of C3 to C20, in the main chain, alkoxyalkyl, arylalkyl and cycloalkylalkyl with said number of carbon atoms in alkyl moiety for alkoxyalkyl, and for arylalkyl with said number of carbon atoms in aryl moiety is from C6 to C18, and the alkyl moiety having a chain length from C1 to C20, cycloalkyl comprising from C3 to C20, wherein W, X. Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl and trifluoroalkanoyl, wherein the number of carbon atoms as defined in claim 1, substantially exclusive of the administration of any antiviral agent comprising a nucleoside, a nucleotide, an immunomodulator, or immunostimulant. 10. The method of claim 9, wherein R is a straight chain alkyl having a chain length of C7 to C20 and W, X, Y and Z are each hydrogen. 11. The method of claim 10, wherein R is nonyl. 12. The method of claim 9, wherein R is straight chain alkyl having a chain length of C7 to C20 and W, X, Y and Z are each alkanoyl having a chain length of C1-to C20. 13. The method of claim 12, wherein R is nonyl. 14. The method of claim 13, wherein said alkanoyl is butanoyl. 15. The method of claim 1, wherein said one N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compound is selected from the group consisting of: N-(n-heptyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-octyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-undecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-dodecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-tridecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-tetradecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-pentadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-hexadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-heptadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-octadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-nonadecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-eicosyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(n-heptyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-octyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-nonyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-undecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-dodecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-tridecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-tetradecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-pentadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-hexadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-heptadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-octadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-nonadecyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(n-eicosyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(2-ethylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(4-ethylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(5-methylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(3-propylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(1-pentyl pentylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(1-butylbutylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(7-methlyloctyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(8methylonyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(9-methyldecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(10-methylundecyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(6-cyclohexylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol; N-(4-cyclohexylbutyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(2-cyclohexylethyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(1-cyclohexylmethyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(1-phenylmethyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(3-phenylpropyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(3-(4-methyl)phenylpropyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(6-phenylhexyl)-1,5-dideoxy-1,5-imino-D-glucitol, tetrabutyrate; N-(7-oxa-n-decyl)-1,5-dideoxy-1,5-imino-D-glucitol; N