Glucamine salts for treating hepatitis virus infections
First Claim
Patent Images
1. A salt of an N-substituted glucamine compound and an antibacterial compound selected from the group consisting of (−
- )-2′
-deoxy-3′
-thiocytidine-5′
-triphosphate (3TC), 1-(2′
-deoxy-2′
-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine triphosphate (FIACTP), acyclovir triphosphate (ACVTP), E-5-(2-bromovinyl)-2′
-deoxyuridine triphosphate, and 9-beta-D-arabinofuranosyl-9H-purine-6-amine-5′
-monophosphate monohydrate (Ara-AMP), said glucamine compound corresponding to Formula I;
wherein;
R and R5 are independently selected from the group consisting of substituted alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, cycloalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylalkenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, haloalkoxyalkynylcarbonyl, or hydroxysulfonealkylcarbonyl, wherein R and R5 are independently substituted by one or more substituents selected from the group consisting of amino, substituted amino, disubstituted amino, heterocyclo containing at least one nitrogen, or heteroaryl containing at least one basic nitrogen, R and R5 are independently selected from the group consisting of substituted alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, cycloalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylalkenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, haloalkoxyalkynylcarbonyl, or hydroxysulfonealkylcarbonyl, wherein R and R5 are independently substituted by one or more substituents selected from the group consisting of amino, substituted amino, disubstituted amino, heterocyclo containing at least one nitrogen, or heteroaryl containing at least one basic nitrogen, 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;
and D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring.
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Abstract
N-Substituted glucamine compounds of formula I are effective in treatment of hepatitis infections, including hepatitis B and hepatitis C. In treating hepatitis infections the compounds of formular I may be used alone, or in combinatioin with another antiviral agent selected from among nucleosides, nucleotides, immunomodulators, immunostimulants or various combination of such other agents.
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Citations
13 Claims
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1. A salt of an N-substituted glucamine compound and an antibacterial compound selected from the group consisting of (−
- )-2′
-deoxy-3′
-thiocytidine-5′
-triphosphate (3TC), 1-(2′
-deoxy-2′
-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine triphosphate (FIACTP), acyclovir triphosphate (ACVTP), E-5-(2-bromovinyl)-2′
-deoxyuridine triphosphate, and 9-beta-D-arabinofuranosyl-9H-purine-6-amine-5′
-monophosphate monohydrate (Ara-AMP), said glucamine compound corresponding to Formula I;
wherein; R and R5 are independently selected from the group consisting of substituted alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, cycloalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylalkenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, haloalkoxyalkynylcarbonyl, or hydroxysulfonealkylcarbonyl, wherein R and R5 are independently substituted by one or more substituents selected from the group consisting of amino, substituted amino, disubstituted amino, heterocyclo containing at least one nitrogen, or heteroaryl containing at least one basic nitrogen, R and R5 are independently selected from the group consisting of substituted alkenylcarbonyl, alkynylcarbonyl, arylalkylcarbonyl, aryloxyalkylcarbonyl, haloalkylcarbonyl, hydroxyalkylcarbonyl, haloalkyloxyalkylcarbonyl, cycloalkyloxyalkylcarbonyl, alkoxyalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkylcarbonyl, aryloxyalkoxyalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyloxyalkylcarbonyl, alkylcarbonylaminoalkylcarbonyl, arylcarbonylaminoalkylcarbonyl, alkoxycarbonylaminoalkylcarbonyl, aminocarbonylaminoalkylcarbonyl, aminothiocarbonyl, aminoalkylcarbonyl, arylalkenylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, aminocarbonylalkylcarbonyl, aminothiocarbonylalkylcarbonyl, aminosulfonealkylcarbonyl, arylalkynylcarbonyl, heterocycloalkylcarbonyl, heteroarylthiaalkylcarbonyl, heterocyclooxyalkylcarbonyl, heterocyclothiaalkylcarbonyl, arylthiaalkylcarbonyl, monohaloalkylcarbonyl, cycloalkylalkyloxyalkylcarbonyl, cycloalkylcarbonyl, cycloalkenylcarbonyl, arylcarbonyl, cycloalkenylalkylcarbonyl, cycloalkenylalkenylcarbonyl, cycloalkenylalkynylcarbonyl, bicycloalkenylalkylcarbonyl, tricycloalkenylalkylcarbonyl, tetracycloalkenylalkylcarbonyl, bicycloalkenoxyalkylcarbonyl, tricycloalkenoxyalkylcarbonyl, tetracycloalkenyloxyalkylcarbonyl, cycloalkylalkenylcarbonyl, cycloalkylalkynylcarbonyl, aralkylcarbonyl, aralkoxyalkylcarbonyl, aralkoxyalkenylcarbonyl, aralkoxyalkynylcarbonyl, aralkenoxyalkylcarbonyl, aralkenoxyalkenylcarbonyl, heterocycloalkenylcarbonyl, heteroarylalkenylcarbonyl, heteroarylalkynylcarbonyl, aryloxyalkenylcarbonyl, aryloxyalkynylcarbonyl, dihydroxyalkylcarbonyl, hydroxyalkenylcarbonyl, dihydroxyalkenylcarbonyl, hydroxyalkynylcarbonyl, haloalkoxyalkenylcarbonyl, haloalkoxyalkynylcarbonyl, or hydroxysulfonealkylcarbonyl, wherein R and R5 are independently substituted by one or more substituents selected from the group consisting of amino, substituted amino, disubstituted amino, heterocyclo containing at least one nitrogen, or heteroaryl containing at least one basic nitrogen, 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;
and D and E taken together with the atoms to which they are attached may form a five or six membered heterocyclic ring. - View Dependent Claims (2, 3, 4, 5, 6)
- )-2′
-
7. A salt of an N-substituted glucamine compound and an antibacterial compound selected from the group consisting of (−
- )-2′
-deoxy-3′
-thiocytidine-5′
-triphosphate (3TC), 1-(2′
-deoxy-2′
-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine triphosphate (FIACTP), acyclovir triphosphate (ACVTP), E-5-(2-bromovinyl)-2′
-deoxyuridine triphosphate, and 9-beta-D-arabinofuranosyl-9H-purine-6-amine-5′
-monophosphate monohydrate (Ara-AMP), said glucamine compound corresponding to Formula I;
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, perhaloalkylaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, bicycloalkenylalkyl, tricycloalkenylalkyl, tetracycloalkenylalkyl, bicycloalkenoxyalkyl, tricycloalkenoxyalkyl, tetracycloalkenyloxyalkyl, cycloalkylalkenyl, cycloalkylalkynyl, aralkyl, aralkoxyalkyl, aralkoxyalkenyl, aralkoxyalkynyl, aralkenoxyalkyl, aralkenoxyalkenyl, heterocycloalkenyl, heteroarylalkenyl, heteroarylalkynyl, aryloxyalkenyl, aryloxyalkynyl, dihydroxyalkyl, hydroxyalkenyl, dihydroxyalkenyl, hydroxyalkynyl, haloalkoxyalkenyl, haloalkoxyalkynyl, hydroxysulfonealkyl, R7 or R8, wherein R7=R1X1(R2X2)m(R3X3)n(R4X4)pR13;
R8=R9X9(R10X10)q(R11X11)r(R12X12)sR13 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;
- View Dependent Claims (8, 9, 10, 11, 12, 13)
- )-2′
Specification