The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enh
The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.
대표청구항▼
1. An oligomeric compound having the formula: G-[Ta-L]j-[R-L]q-R-[L-Tb]r-E wherein: each Ta or each Tb is a monomer of formula II: wherein independently for each monomer of formula II: Bx is a heterocyclic base moiety;Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substitu
1. An oligomeric compound having the formula: G-[Ta-L]j-[R-L]q-R-[L-Tb]r-E wherein: each Ta or each Tb is a monomer of formula II: wherein independently for each monomer of formula II: Bx is a heterocyclic base moiety;Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl, substituted C2-C6 alkynyl or substituted acyl;the other of each Ta or each Tb is a modified nucleoside wherein each modified nucleoside independently comprises a 2′-F modified sugar moiety, a 2′-OCH3 modified sugar moiety, a 2′-O—(CH2)2, —OCH3 modified sugar moiety, a 2′-O—CH2-4′ bicyclic modified sugar moiety or a 4′-S modified sugar moiety;each R is a β-D-2′-deoxyribonucleoside;each L is an internucleoside linking group;G and E are each, independently, H, a hydroxyl protecting group or a linked conjugate group;wherein each substituted group is mono or poly substituted with substituent groups independently selected from halogen, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl, OJ1, SJ1, NJ1J2, N3, COOJ1, CN, O—C(═O)—NJ1J2, N(H)C(═NH)NR1R2 or N(H)C(═X)N(H)J2 wherein X is O or S;each J1 and J2 is, independently, H, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl, C1-C6 aminoalkyl, substituted C1-C6 aminoalkyl or a protecting group;q is from 7 to about 15;j is from 1 to about 5; andr is from 1 to about 5. 2. The oligomeric compound of claim 1 wherein each Z is substituted methyl. 3. The oligomeric compound of claim 2 wherein each substituted methyl is, independently, substituted with F, NJ1J2, N3, CN, OJ1, SJ1, O—C(═O)NJ1J2, N(H)C(═NH)NJ1J2 or N(H)C(═O)N(H)J2, wherein each J1 and J2 is, independently H or C1-C6 alkyl. 4. The oligomeric compound of claim 1 wherein each Z is methyl, ethyl or methoxymethyl. 5. The oligomeric compound of claim 4 wherein each Z is methyl. 6. The oligomeric compound of claim 1 wherein each Z is vinyl. 7. The oligomeric compound of claim 1 wherein each monomer having formula II has the configuration: 8. The oligomeric compound of claim 1 wherein each monomer having formula II has the configuration: 9. The oligomeric compound of claim 1 wherein each modified nucleoside has the formula: 10. The oligomeric compound of claim 1 wherein each internucleoside linking group is, independently, a phosphodiester or a phosphorothioate internucleoside linking group. 11. The oligomeric compound of claim 1 wherein each internucleoside linking group is a phosphorothioate internucleoside linking group. 12. The oligomeric compound of claim 1 wherein j and r are each 2. 13. The oligomeric compound of claim 1 wherein q is from about 9 to about 13. 14. The oligomeric compound of claim 1 wherein j and r are each 5. 15. The oligomeric compound of claim 1 wherein q is about 10. 16. The oligomeric compound of claim 1 wherein G and E are each, independently, H or a hydroxyl protecting group. 17. The oligomeric compound of claim 1 wherein one of G and E is a linked conjugate group. 18. The oligomeric compound of claim 1 wherein G and E are each H.
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