MONOMERS AND OLIGONUCLEOTIDES COMPRISING CYCLOADDITION ADDUCT(S)

摘要

The invention features compounds of formula V or XII:;;In one embodiment, the invention relates compounds and processes for conjugating ligand to oligonucleotide. The invention further relates to methods for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, cancers, allergies, autoimmune diseases, immunodeficiencies and immunosuppression.

主权项

1. A compound of formula XI or pharmaceutically acceptable salts thereof: wherein E is absent or C(O), C(O)O, C(O)NH, C(S), C(S)NH, SO, SO2, or SO2NH; R11, R12, R13, R14, R15, R16, R17, and R18 are each independently for each occurrence H, —CH2ORa, or ORb, Ra and Rb are each independently for each occurrence hydrogen, hydroxyl protecting group, optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted alkenyl, optionally substituted heteroaryl, polyethyleneglycol (PEG), a phosphate, a diphosphate, a triphosphate, a phosphonate, a phosphonothioate, a phosphonodithioate, a phosphorothioate, a phosphorothiolate, a phosphorodithioate, a phosphorothiolothionate, a phosphodiester, a phosphotriester, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z1)(Z2)—O-nucleoside, —P(Z1)(Z2)—O-oligonucleotide, —P(Z1)(Z2)-formula (I), —P(Z1)(O-linker-Q-linker-RL)—O-nucleoside, —P(Z1)(O-linker-N3)—O-nucleoside, —P(Z1)(O-linker-CN)—O-nucleoside, —P(Z1)(O-linker-C—R)—O-nucleoside, —P(Z1)(O-linker-cycloalkyne)-O-nucleoside, —P(Z1)(O-linker-RL)—O-oligonucleotide, —P(Z1)(O-linker-Q-linker-RL)—O-oligonucleotide, —P(Z1)(O-linker-RL)—O-oligonucleotide, —P(Z1)(O-linker-N3)—O-oligonucleotide, —P(Z1)(O-linker-CN)—O-oligonucleotide, —P(Z1)(O-linker-C—R)—O-oligonucleotide, —P(Z1)(O-linker-cycloalkyne)-O-oligonucleotide, —P(Z1)(-linker-Q-linker-RL)—O-nucleoside, —P(Z1)(-linker-RL)—O-nucleoside, —P(Z1)(-linker-N3)—O-nucleoside, —P(Z1)(-linker-CN)—O-nucleoside, —P(Z1)(-linker-C—R)—O-nucleoside, —P(Z1)(-linker-cycloalkyne)-O-nucleoside, —P(Z1)(-linker-Q-linker-RL)—O-oligonucleotide, (Z1)(-linker-RL)—O-oligonucleotide, —P(Z1)(-linker-N3)—O-oligonucleotide, —P(Z1)(-linker-CN)—O-oligonucleotide, —P(Z1)(-linker-C—R)—O-oligonucleotide or —P(Z1)(-linker-cycloalkyne)-O-oligonucleotide; R30 is independently for each occurrence-linker-Q-linker-RL, -linker-RL or R31; Q is independently for each occurrence X1 is O, S, CF2, or CH2; Y1, Y2 and Y3 are each independent CRP, N, O, or S; W1 is CH or N; R100, R200, R300 and R400 are each independently hydrogen, halogen, ORN, CRP2, acyl, phosphonyl, sulfonyl; or alternatively, R100 and R200 or R300 and R400 are taken together to form an aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl; RL is hydrogen or a ligand; RN is independently for each occurrence H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroaryl or an amino protecting group; RP is independently for each occurrence occurrence H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted cycloalkyl or optionally substituted heteroaryl; R8 is N or CR9; R9 is H, optionally substituted alkyl or silyl; R31 is —C(O)CH(N(R32)2)(CH2)hN(R32)2; R32 is independently for each occurrence H, -linker-Q-linker-RL, -linker-RL or R31; h is independently for each occurrence 1-20; and Z1 and Z2 are each independently for each occurrence O, S or optionally substituted alkyl; provided that formula (XI) comprises at least one Q moiety.