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US 7,750,131 B2Granted
5′-modified bicyclic nucleic acid analogs
AssigneeIsis Pharmaceuticals, Inc.
InventorsPunit P. Seth, Eric E. Swayze, Balkrishen Bhat
Life of this patent
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Abstract
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.
Claims40
An oligomeric compound having the formula:
- G-[T-L]j-[R-L]q-R-[L-T]r-E
- wherein:
- each T is a monomer of formula II:
- wherein independently for each monomer having 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;
- 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 0 or from 1 to about 5;
- r is 0 or from 1 to about 5;
- the sum of j and r is at least 1;
- and
- the sum of j, q and r is from 7 to 39.
14 more elements
An oligomeric compound comprising at least one monomer having formula I:
- wherein independently for each monomer having formula I:
- Bx is a heterocyclic base moiety;
- one of T3 and T4 is an internucleoside linking group attaching the monomer having formula I to the oligomeric compound and the other of T3 and T4 is H, a hydroxyl protecting group, a linked conjugate group or an internucleoside linking group attaching the monomer having formula I to the oligomeric compound;
- 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;
- 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;
- said oligomeric compound comprising at least one monomeric subunit that is other than a monomer having formula I, selected from a β-D-ribonucleoside, a β-D-2′-deoxyribonucleoside and a modified nucleoside wherein said modified nucleoside comprises at least a sugar substituent group, a 4′-S group or a bicyclic modified sugar;
- and
- wherein said oligomeric compound comprises from 8 to 40 nucleosides and/or modified nucleosides or mimetics in length.
6 more elements
Dependencies are inferred from the claim text.