Oligonucleotides containing 2′-O-modified purines
View Patent ↗Compounds are provided containing purine nucleotides that bear moieties X at the 2′ position thereof wherein X is R 1 —(R 2 ) n ; R 1 is C 3 -C 20 alkyl, C 4 -C 20 alkenyl or C 2 -C 20 alkynyl; R 2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6. Such compounds are useful for modulating the synthesis of proteins.
1. A compound having the structure:
wherein
X is R 1 —(R 2 ) n ;
R 1 is C 2 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl and n is 1 to 6;
R 2 is halogen, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, imidazole, N-phthalimido, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether; and
either one of T 3 and T 5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T 3 and T 5 is a nucleotide or both T 3 and T 5 are nucleotides.
2. A compound having the structure:
wherein
X is R 1 —(R 2 ) n ;
R 1 is C 1 -C 20 alkyl, C 4 -C 20 alkenyl, or C 2 -C 20 alkynyl;
R 2 is halogen, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, imidazole, N-phthalimido, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether;
either one of T 3 and T 5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T 3 and T 5 is a nucleotide, or both T 3 and T 5 are nucleotides; and
n is an integer from 1 to 6.
3. The compound of claim 1 wherein R 1 is C 4 -C 20 alkyl.
4. The compound of claim 1 wherein R 1 is C 5 -C 20 alkyl.
5. The compound of claim 1 wherein R 1 is C 3 -C 20 alkyl and n is 1.
6. The compound of claim 1 wherein R 1 is C 4 -C 20 alkenyl and n is 1.
7. The compound of claim 1 wherein R 1 is C 2 -C 20 alkynyl and n is 1.
8. The compound of claim 1 wherein R 1 is C 2 -C 20 alkyl and n is 1 to 6.
9. The compound of claim 1 wherein R 1 is C 2 -C 20 alkenyl and n is 1 to 6.
10. The compound of claim wherein R 1 is C 2 -C 20 alkynyl and n is 1 to 6.
11. The compound of claim 2 wherein R 1 is C 1 -C 20 alkyl.
12. The compound of claim 2 wherein R 1 is C 4 -C 20 alkenyl.
13. The compound of claim 2 wherein R 1 is C 2 -C 20 alkynyl.
14. A compound having the structure:
wherein
X is R 1 —(R 2 ) n ;
R 1 is C 4 -C 20 alkyl, C 4 -C 20 alkenyl, or C 2 -C 20 alkynyl and n is 0; or R 1 is C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl and n is 1 to 6;
R 2 is hydroxyl, thiol, keto, carboxyl, or amino; and
either one of T 3 and T 5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T 3 and T 5 is a nucleotide or both T 3 and T 5 are nucleotides.
15. A compound having the structure:
wherein
X is R 1 —(R 2 ) n ;
R 1 is C 1 -C 20 alkyl, C 4 -C 20 alkenyl, or C 2 -C 20 alkynyl;
R 2 is hydroxyl, thiol, keto, carboxyl, or amino;
either one of T 3 and T 5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T 3 and T 5 is a nucleotide, or both T 3 and T 5 are nucleotides; and
n is an integer from 0 to 6.