Prodrugs of deoxynucleosides for treatment of diseases caused by unbalanced nucleotide pools

A method for treating a disease or disorder characterized by unbalanced nucleotide pools in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one prodrug of Formula I:

• wherein
• Base refers to an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group;
• R1 is selected from the group consisting of optionally substituted acyl, optionally substituted O-linked amino acid,
• Y and Z are each independently selected from O and S;
• R4 is selected from hydrogen, optionally substituted C1-24 alkyl, optionally substituted C2-24 alkenyl, optionally substituted C2 -24 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted C3-6 cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryl (C1-6) alkyl,
• R5, R6 and R7 are each independently selected from optionally substituted C1-24 alkyl, optionally substituted C2-24 alkenyl, optionally substituted C2-24 alkynyl, optionally substituted C3-6 cycloalkyl, and optionally substituted C3-6 cycloalkenyl;
• R8, R9, R11 and R12 are each independently selected from hydrogen, optionally substituted C1-24 alkyl and optionally substituted aryl;
• R10 and R13 are each independently selected from hydrogen, optionally substituted C1-24 alkyl and optionally substituted aryl, an optionally substituted —O—C1-24 alkyl, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl, an optionally substituted —O-monocyclic heterocyclyl;
• R14, R15 and R19 are each independently selected from hydrogen, an optionally substituted C1-24 alkyl and an optionally substituted aryl;
• R16 and R17 are each independently selected from —CN, optionally substituted C2-8 organylcarbonyl, C2-8 alkoxycarbonyl and C2-8 organylaminocarbonyl;
• R18 is selected from hydrogen, optionally substituted C1-24 alkyl, optionally substituted C2-24 alkenyl, optionally substituted C2-24 alkynyl;
• optionally substituted C3-6 cycloalkyl and optionally substituted C3-6 cycloalkenyl;
• R20 and R21 are each independently selected from hydrogen, optionally substituted C1-24 alkyl, optionally substituted C2-24 alkenyl, optionally substituted C2-24 alkynyl;
• optionally substituted C3-6 cycloalkyl and optionally substituted C3-6 cycloalkenyl;
• and
• n, m and p are each independently selected from 0, 1, 2, or 3.