Cyclic-disulfide modified phosphate based oligonucleotide prodrugs

A compound comprising a structure of formula (I):

• - (I)
• wherein the has the structure of:
• wherein:
• R1 is O or S, and is bonded to the P atom of the ;
• R2, R4, R6, R7, R8, and R9 are each independently H, halo, OR13 or alkylene-OR13, N(R′)(R″) or alkylene-N(R′)(R″), alkyl, C(R14)(R15)(R16) or alkylene-C(R14)(R15)(R16), alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, each of which can be optionally substituted by one or more RSub groups;
• R3 and R5 are each independently H, halo, OR13 or alkylene-OR13, N(R′)(R″) or alkylene-N(R′)(R″), alkyl, C(R14)(R15)(R16) or alkylene-C(R14)(R15)(R16), alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, each of which can be optionally substituted by one or more Rsub groups;
• or R3 and R5, together with the adjacent carbon atoms and the two sulfur atoms, form a second ring;
• G is O, N(R′), S, or C(R14)(R15);
• n is an integer of 0-6;
• R13 is independently for each occurrence H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, ω-amino alkyl, ω-hydroxy alkyl, ω-hydroxy alkenyl, alkylcarbonyl, or arylcarbonyl, each of which can be optionally substituted with one or more Rsub groups;
• R14, R15, and R16 are each independently H, halo, haloalkyl, alkyl, alkaryl, aryl, heteroaryl, aralkyl, hydroxy, alkyloxy, aryloxy, N(R′)(R″);
• R′ and R″ are each independently H, alkyl, alkenyl, alkynyl, aryl, hydroxy, alkyloxy, ω-amino alkyl, ω-hydroxy alkyl, ω-hydroxy alkenyl, or ω-hydroxy alkynyl, each of which can be optionally substituted with one or more Rsub groups;
• and
• Rsub is independently for each occurrence halo, haloalkyl, alkyl, alkaryl, aryl, aralkyl, hydroxy, alkyloxy, aryloxy, oxo, nitro, amino, acylamino, alkylcarbamoyl, arylcarbamoyl, alkylamino, aminoalkyl, alkoxycarbonyl, carboxy, hydroxyalkyl, alkanesulfonyl, arenesulfonyl, alkanesulfonamido, arenesulfonamido, aralkylsulfonamido, alkylcarbonyl, arylcarbonyl, acyloxy, cyano, or ureido.