Glucamine salts for treating hepatitis virus infections

A method for treating a hepatitis virus infection in a mammal, comprising administering to said mammal an anti-hepatitis virus effective amount of an antiviral composition comprising at least one glucamine compound of Formula I or a pharmaceutically acceptable salt thereof

• 117
• wherein:
• R and R5 are independently selected from the group consisting of H, aryloxyalkoxyalkyl, alkylcarbonyloxyalkyl, alkyl, arylcarbonyloxyalkyl, aminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, aminothiocarbonylaminoalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, arylalkyl, arylalkenyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aminothiocarbonylalkyl, aminosulfonealkyl, arylalkynyl, heterocycloalkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, aryloxyalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, carbonyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, perhaloalkylaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, bicycloalkenylalkyl, tricycloalkenylalkyl, tetracycloalkenylalkyl, bicycloalkenoxyalkyl, tricycloalkenoxyalkyl, tetracycloalkenyloxyalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aralkyl, aralkoxyalkyl, aralkoxyalkenyl, aralkoxyalkynyl, aralkenoxyalkyl, aralkenoxyalkenyl, heterocycloalkenyl, heteroarylakenyl, heteroarylalkynyl, aryloxyalkenyl, aryloxyalkynyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkenyl, dihydroxyalkenyl, hydroxyalkynyl, haloalkoxyalkenyl, haloalkoxyalkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, hydroxyalkylcarbonyl, hydroxysulfonealkyl, cycloalkylcarbonyl, cycloalkylalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylakenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, and haloalkoxyalkynylcarbonyl, hydroxysulfonealkylcarbonyl, R7 or R8, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• wherein the main chain in R or R5 contains between one and twenty atoms.

An N-substituted glucamine compound of Formula I or a pharmaceutically acceptable salt thereof:

• 118
• wherein:
• R is aryloxyalkyl, monohaloalkyl, haloalkyloxyalkyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, arylalkyloxycarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, perhaloalkylaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, bicycloalkenylalkyl, tricycloalkenylalkyl, tetracycloalkenylalkyl, bicycloalkenoxyalkyl, tricycloalkenoxyalkyl, tetracycloalkenyloxyalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aralkyl, aralkoxyalkyl, aralkoxyalkenyl, aralkoxyalkynyl, aralkenoxyalkyl, aralkenoxyalkenyl, heterocycloalkenyl, heteroarylakenyl, heteroarylalkynyl, aryloxyalkyl, aryloxyalkenyl, aryloxyalkynyl, hydroxyalkyl, dihydroxyalkyl,hydroxyalkenyl, dihydroxyalkenyl, hydroxyalkynyl, haloalkoxyalkenyl, haloalkoxyalkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, hydroxyalkylcarbonyl, amino(alkyl), alkanoyl(amino)alkyl, (amino)carbonylalkyl, hydroxysulfonealkyl, (amino)carbonylaminoalkyl, or R5, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• wherein the main chain in R or R5 contains between one and twenty atoms;
• the main chain of each of R7 and R8 contains between four and twenty atoms and either of R1X1 or R9X9;
• provided that R and R5 are not both hydrido.

An N-substituted glucamine compound of Formula I or a pharmaceutically acceptable salt thereof:

• 119
• wherein:
• R and R5 are independently selected from the group consisting of alkyl, aminoalkyl, arylcarbonylaminoalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycloalkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonylaminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, R7 or R8,
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring.

An N-substituted glucamine compound of Formula I or a pharmaceutically acceptable salt thereof:

• 120
• wherein:
• R and R5 are independently selected from the group consisting of H, aryloxyalkoxyalkyl, alkylcarbonyloxyalkyl, alkyl, arylcarbonyloxyalkyl, aminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, aminothiocarbonylaminoalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, arylalkyl, arylalkenyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aminothiocarbonylalkyl, aminosulfonealkyl, arylalkynyl, heterocycloalkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, aryloxyalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, carbonyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonylaminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl and R5 is H, alkyl, alkenyl, alkynyl, alkoxyalkyl, arylalkyl, aryloxyalkyl, cycloalkyl, cycloalkylalkyl, aryloxyalkyl, haloalkyl, hydroxyalkyl, haloalkyloxyalkyl, cycloalkyloxyalkyl cycloalkylalkyloxyalkyl, R7 or R8, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• wherein the main chain in R or R5 contains between one and twenty atoms;
• the main chain of each of R7 and R8 contains between four and twenty atoms and either of R1X1 or R9X9;
• provided that not both of R and R5 are hydrido.

An N-substituted glucamine compound of Formula I or a pharmaceutically acceptable salt thereof:

• 121
• wherein:
• R and R5 are independently selected from the group consisting of aryloxyalkoxyalkyl, alkylcarbonyloxyalkyl, arylcarbonyloxyalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, aminothiocarbonylaminoalkyl, alkoxyalkyl, hydroxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aminothiocarbonylalkyl, aminosulfonealkyl, heterocycloalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, carbonyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonylaminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, R7 or R8, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• wherein the main chain in R or R5 contains between one and twenty atoms;
• the main chain of each of R7 and R8 contains between four and twenty atoms and either of R1X1 or R9X9;
• provided that not both of R and R5 are hydrido.

A pharmaceutical composition comprising an anti-viral compound comprising an N-substituted glucamine compound or a pharmaceutically acceptable salt thereof and another antiviral compound selected from the group consisting of a nucleoside, a nucleotide, an immunomodulator, an immunostimulant, and mixtures thereof, said glucamine compound corresponding to Formula I:

• 122
• wherein:
• R and R5 are independently selected from the group consisting of H, aryloxyalkoxyalkyl, alkylcarbonyloxyalkyl, alkyl, arylcarbonyloxyalkyl, aminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, aminothiocarbonylaminoalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, arylalkyl, arylalkenyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aminothiocarbonylalkyl, aminosulfonealkyl, arylalkynyl, heterocycloalkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, aryloxyalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, carbonyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, perhaloalkylaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, bicycloalkenylalkyl, tricycloalkenylalkyl, tetracycloalkenylalkyl, bicycloalkenoxyalkyl, tricycloalkenoxyalkyl, tetracycloalkenyloxyalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aralkyl, aralkoxyalkyl, aralkoxyalkenyl, aralkoxyalkynyl, aralkenoxyalkyl, aralkenoxyalkenyl, heterocycloalkenyl, heteroarylakenyl, heteroarylalkynyl, aryloxyalkenyl, aryloxyalkynyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkenyl, dihydroxyalkenyl, hydroxyalkynyl, haloalkoxyalkenyl, haloalkoxyalkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, hydroxyalkylcarbonyl, hydroxysulfonealkyl, cycloalkylcarbonyl, cycloalkylalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylakenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, and haloalkoxyalkynylcarbonyl, hydroxysulfonealkylcarbonyl, R7 or R8, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring.

A salt of an N-substituted glucamine compound and an antiviral compound selected from the group consisting of a nucleoside having an acid moiety and a nucleotide, said glucamine compound corresponding to Formula I:

• 123
• wherein:
• R and R5 are independently selected from the group consisting of H, aryloxyalkoxyalkyl, alkylcarbonyloxyalkyl, alkyl, arylcarbonyloxyalkyl, aminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, aminothiocarbonylaminoalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, arylalkyl, arylalkenyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aminothiocarbonylalkyl, aminosulfonealkyl, arylalkynyl, heterocycloalkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, aryloxyalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, carbonyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, perhaloalkylaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, bicycloalkenylalkyl, tricycloalkenylalkyl, tetracycloalkenylalkyl, bicycloalkenoxyalkyl, tricycloalkenoxyalkyl, tetracycloalkenyloxyalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aralkyl, aralkoxyalkyl, aralkoxyalkenyl, aralkoxyalkynyl, aralkenoxyalkyl, aralkenoxyalkenyl, heterocycloalkenyl, heteroarylakenyl, heteroarylalkynyl, aryloxyalkenyl, aryloxyalkynyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkenyl, dihydroxyalkenyl, hydroxyalkynyl, haloalkoxyalkenyl, haloalkoxyalkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, hydroxyalkylcarbonyl, hydroxysulfonealkyl, cycloalkylcarbonyl, cycloalkylalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylakenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, and haloalkoxyalkynylcarbonyl, hydroxysulfonealkylcarbonyl, R7 or R8, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring.

A method for treating a hepatitis virus infection in a mammal, comprising administering to said mammal a first amount of at least one N-substituted glucamine compound of Formula I or a pharmaceutically acceptable salt thereof:

• 124
• wherein:
• R and R5 are independently selected from the group consisting of H, aryloxyalkoxyalkyl, alkylcarbonyloxyalkyl, alkyl, arylcarbonyloxyalkyl, aminoalkyl, alkylcarbonylaminoalkyl, arylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, aminocarbonylaminoalkyl, aminothiocarbonylaminoalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyalkyl, arylalkyl, arylalkenyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, aminothiocarbonylalkyl, aminosulfonealkyl, arylalkynyl, heterocycloalkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkyl, heterocyclooxyalkyl, heterocyclothiaalkyl, aryloxyalkyl, arylthiaalkyl, haloalkyl, haloalkyloxyalkyl, carbonyl, cycloalkyloxyalkyl, cycloalkylalkyloxyalkyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, aminoalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, perhaloalkylaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, bicycloalkenylalkyl, tricycloalkenylalkyl, tetracycloalkenylalkyl, bicycloalkenoxyalkyl, tricycloalkenoxyalkyl, tetracycloalkenyloxyalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aralkyl, aralkoxyalkyl, aralkoxyalkenyl, aralkoxyalkynyl, aralkenoxyalkyl, aralkenoxyalkenyl, heterocycloalkenyl, heteroarylakenyl, heteroarylalkynyl, aryloxyalkenyl, aryloxyalkynyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkenyl, dihydroxyalkenyl, hydroxyalkynyl, haloalkoxyalkenyl, haloalkoxyalkynyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, hydroxyalkylcarbonyl, hydroxysulfonealkyl, cycloalkylcarbonyl, cycloalkylalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylakenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, and haloalkoxyalkynylcarbonyl, hydroxysulfonealkylcarbonyl, R7 or R8, wherein
• R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
• R8=R9X9(R10X10)q(R11X11)r(R12X12)R13
• R1 and R9 are independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, hydrogen or haloalkyl;
• R2, R3, R4, R10, R11, R12 and R13 are independently selected from the group consisting of alkylene, alkenylene, alkynylene or haloalkylene;
• X1, X2, X3, X4, X9, X10, X11 and X12 are independently oxygen, sulfur, sulfoxide or sulfone;
• m, n, p, q, r and s are independently 0, 1, 2 or 3;
• m+n+p≦3
• q+r+s≦3
• A, B, C, D and E are independently hydrido, lower alkyl or acyl;
• A and B taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• B and C taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and D taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• C and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring;
• wherein the main chain in R or R5 contains between one and twenty atoms;
• the main chain of each of R7 and R8 contains between four and twenty atoms and either of R1X1 or R9X9;
• and
• a second amount of an antiviral compound selected from the group consisting of a nucleoside antiviral compound, a nucleotide antiviral compound, and immunomodulator, an immunostimulant, and mixtures thereof.