Mutagenic nucleoside analogs for the treatment of viral disease

A method of increasing the mutation rate of a virus, comprising administering the compound to a virally infected cell, wherein the compound has the structure:

• 10
• wherein,
• R1 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• R2 is H, halogen, NR21R22, or a group cleavable under biological conditions;
• and
• R8, R9, R21, and R22 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• and wherein the compound is incorporated by a polymerase into a genomic nucleic acid encoding the virus, thereby inducing the virus to mutate.

A method of increasing the mutation rate of a virus, comprising administering the compound to a virally infected cell, wherein the compound has the structure:

• 12
• wherein,
• R1 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• R2 is H, halogen, NR21R22, or a group cleavable under biological conditions;
• and
• R10 and R11 are members independently selected from O, and NR12, wherein
• R12, R21 and R22 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• and wherein the compound is incorporated by a polymerase into a genomic nucleic acid encoding the virus, thereby inducing the virus to mutate.

A method of increasing the mutation rate of a virus, comprising administering the compound to a virally infected cell, wherein the compound has the structure:

• 14
• wherein,
• R13, R14 and R15 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R16 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• A and B are members independently selected from N, and CR17, wherein
• R17 is a member selected from H, OH, CN, N3, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, halogen NR18, and SR19, wherein
• R18 and R19 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• and wherein the compound is incorporated by a polymerase into a genomic nucleic acid encoding the virus, thereby inducing the virus to mutate.

A compound having the structure:

• 17
• wherein,
• R1 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• R2 is H, halogen, NR21R22, or a group cleavable under biological conditions;
• R3 is selected from O, NR4, NOR4 and NN(R5)C(O)R4 in which,
• R4, R5, R21 and R22 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

A compound having the structure:

• 20
• wherein,
• R1 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• R2 is H, halogen, NR21R22, or a group cleavable under biological conditions;
• and
• R8, R9, R21, and R22 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

A compound having the structure:

• 22
• wherein,
• R1 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• R2 is H, halogen, NR21R22, or a group cleavable under biological conditions;
• R10 and R11 are members independently selected from O, and NR12, wherein
• R12, R21 and R22 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

A compound having the structure:

• 24
• wherein,
• R13, R14 and R15 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• R16 is a member selected from H and a sugar residue, which is in a configuration selected from D-, L- and combinations thereof;
• and in an anomeric form selected from α-, β- and combinations thereof;
• A and B are members independently selected from N, and CR17, wherein
• R17 is a member selected from H, OH, CN, N3, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, halogen NR18, and SR19, wherein
• R18 and R19 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.