Vitamin b6 derivatives of nucleotides, acyclonucleotides and acyclonucleoside phosphonates

Abstract

Provided herein are compounds, compositions, and methods of using them to treat infections, neoplastic disease, inflammatory disease, and pain. Such compounds are nucleotides, acyclonucleotides, and ANP phosphonates conjugated with forms and/or moieties of Vitamin B6 for delivery past the cell membrane and into the cell.

What is claimed is: 
     
         1 . A compound having the general structure: 
       
         
           
           
               
               
           
         
         wherein R 1  is a 5′-nucleosidyl or acyclonucleosidyl residue compound having anticancer, antiviral, antiparasitic or antiinflammatory activity; 
         X and Y are independently O, S, or N; and 
         R 2  and R 3  are independently chosen from the group consisting of H, phenyl, alkyl, aryl, heteroaryl, and a vitamin B6 moiety having one of the structures 
       
       
         
           
           
               
               
           
         
         wherein at least one of R 2  and R 3  is a vitamin B6 moiety. 
       
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The compound of  claim 1 , wherein R 1  is selected from the group of compounds of the following structures: 
       
         
           
           
               
               
           
         
         wherein B is a modified or unmodified nucleic base; 
         E is O, C, N, or S; 
         A is C, S, or O; and 
         R 4 , R 5 , R 6 , R 7 , R 8  and R 9  are independently selected from the group consisting of H, OH, F, NH 2 , N 3 , alkyl, alkenyl, and alkynyl. 
       
     
     
         6 . The compound of  claim 1 , wherein R 1  is selected from the group of compounds of the following structures: 
       
         
           
           
               
               
           
         
         wherein B is a modified or unmodified nucleic base, 
         E is O or C; and 
         R 10  and R 11  are independently selected from the group consisting of H, OH, F, NH 2 , N 3 , alkyl, alkenyl, and alkynyl. 
       
     
     
         7 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier, diluent, excipient, or a combination thereof. 
     
     
         8 . A method of delivering nucleoside- or acyclonucleoside-monophosphates or ANPs into the cell, by using the compounds of  claim 1 . 
     
     
         9 . A method of ameliorating or treating a disease caused by bacterial infections comprising administering to a subject suffering of said disease a therapeutically effective amount of a compound of  claim 1 . 
     
     
         10 . A method of ameliorating or treating a disease caused by fungal infections comprising administering to a subject suffering of said disease a therapeutically effective amount of a compound of  claim 1 . 
     
     
         11 . A method of ameliorating or treating a viral disease comprising administering to a subject suffering of said disease a therapeutically effective amount of a compound of  claim 1 . 
     
     
         12 . The method of  claim 11 , where said viral disease is caused by virus selected from the group consisting of Alphaviridae, Arbovirus, Astrovirus, Bunyaviridae, Coronaviridae, Filoviridae, Flaviviridae, Hepadnaviridae, Herpesviridae, Alphaherpesvirinae, Betaherpesvirinae, Gammaherpesvirinae, Norwalk Virus, Astroviridae, Caliciviridae, Orthomyxoviridae, Paramyxoviridae, Paramyxoviruses, Rubulavirus, Morbillivirus, Papovaviridae, Parvoviridae, Picornaviridae, Aphthoviridae, Cardioviridae, Enteroviridae, Coxsackie virus, Polio Virus, Rhinoviridae, Phycodnaviridae, Poxyiridae, Reoviridae, Rotavirus, Retroviridae, A-Type Retrovirus, Immunodeficiency Virus, Leukemia Virus, Avian Sarcoma Virus, Rhabdovirus, Rubiviridae, and Togaviridae. 
     
     
         13 . The method of  claim 11 , wherein the viral disease is a hepatitis C viral infection or a HIV viral infection. 
     
     
         14 . A method of ameliorating or treating a neoplastic disease comprising administering to a subject suffering of said disease a therapeutically effective amount of a compound of  claim 1 . 
     
     
         15 . The method of  claim 14 , where said neoplastic disease is cancer. 
     
     
         16 . The method of  claim 14 , where said neoplastic disease is leukemia. 
     
     
         17 . A method of ameliorating or treating an inflammatory disease comprising administering to a subject suffering of said disease a therapeutically effective amount of a compound of  claim 1 . 
     
     
         18 . The method of  claim 17 , where said inflammatory disease is Multiple Sclerosis. 
     
     
         19 . A method of ameliorating or treating a parasitic disease comprising administering to a subject suffering of said disease a therapeutically effective amount of a compound of  claim 1 . 
     
     
         20 . The method of  claim 19  where said parasitic disease is Chaga's disease. 
     
     
         21 . A method of ameliorating or treating pain comprising administering to a subject suffering of said condition a therapeutically effective amount of a compound of  claim 1 . 
     
     
         22 . The compound according to  claim 1 , or a pharmaceutical composition thereof, for use as a medicament. 
     
     
         23 . The compound according to  claim 1 , or a pharmaceutical composition thereof, for use in the therapy of a disease caused by a bacterial infection, a fungal infection, a viral disease, a neoplastic disease, an inflammatory disease, a parasitic disease or pain. 
     
     
         24 . Use of a compound according to any of  claim 1 , or a pharmaceutical composition thereof, for use for the manufacture of a medicament for the treatment of a disease caused by a bacterial infection, a fungal infection, a viral disease, a neoplastic disease, an inflammatory disease, a parasitic disease or pain.