CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods

A CpG oligonucleotide prodrug comprising a CpG oligonucleotide that has a poly-G tail at the 3′-end of the oligonucleotide and a thermolabile substituent bonded thereto, wherein the thermolabile substituent is bonded to the non-bridging oxygen atom of a deoxyguanosine phosphate, phosphorothioate, or phosphoroselenoate diester present in the poly-G tail in an amount sufficient to inhibit G-tetrad formation, wherein the CpG oligonucleotide that has a poly-G tail forms a tetraplex in the absence of the thermolabile substituent, and, wherein the thermolabile substituent is of the formula:

• wherein:
• R2, R2′, R3 and R3′are the same or different and each is H, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl, or R2 or R2′, in combination with R3 or R3′, together with the carbon atoms to which they are bonded, comprise a cyclic substituent of the formula:
• wherein p is an integer from 0-6 and a-d are the same or different and each is selected from the group consisting of H, an alkyl, a nitro, a dialkylamino, an alkoxy, an alkylthio, a cyano and a halogen;
• Z is O, S, NR4a, CR4aR4a′or CR4aR4a′CR4bR4b′, wherein R4a, R4a′, R4b and R4b′ are the same or different and each is H, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl;
• and
• Y is CH2R1 or C(X)H wherein X is O or S, and R1 is H, R1a, OR1a, SR1a or NR1aR1a′, wherein R1a and R1a′are the same or different and each is H, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl;
• wherein R1a, R1a′, R2, R2′,R3, R3′, R4a, R4a′,R4b and R4b′ are unsubstituted or substituted with one or more substituents, which are the same or different, selected from the group consisting of OR5, SR5, CN, NO2, N3, and a halogen, wherein R5 is H or an alkyl.