The present disclosure describes bis-modified bicyclic nucleosides and oligomeric compounds that can be prepared comprising at least one of these bis-modified bicyclic nucleosides. More particularly, the bis-modified bicyclic nucleosides have at least one substituent group at the 5′-methylene and on
The present disclosure describes bis-modified bicyclic nucleosides and oligomeric compounds that can be prepared comprising at least one of these bis-modified bicyclic nucleosides. More particularly, the bis-modified bicyclic nucleosides have at least one substituent group at the 5′-methylene and on the bridge methylene and can be chiral. These bis-modified bicyclic nucleosides are expected to be useful for enhancing one or more property of oligomeric compounds including for example enhancing nuclease resistance.
대표청구항▼
1. 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 V: wherein independently for each monomer having Formula V: Bx is a heterocyclic base moiety;one of Z1 and Z2 is H, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6
1. 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 V: wherein independently for each monomer having Formula V: Bx is a heterocyclic base moiety;one of Z1 and Z2 is H, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl or substituted C2-C6 alkynyl and the other one of Z1 and Z2 is C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl or substituted C2-C6 alkynyl;one of Q1 and Q2 is H, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl, thiol or substituted thiol and the other one of Q1 and Q2 is C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl, thiol or substituted thiol;or Q1 and Q2 together are methylene (═CH2);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, a linked conjugate group or a 5′ or 3′-terminal group;wherein each substituted group is mono or poly substituted with substituent groups independently selected from halogen, OJ1, SJ1, NJ1J2, N3, COOJ1, CN, O—C(═O)NJ1J2, N(H)C(═NH)NJ1J2, N(H)C(═O)N(H)J2 or N(H)C(═S)N(H)J2;each J1 and J2 is, independently, H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 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; andthe sum of j and r is at least 1. 2. The oligomeric compound of claim 1 wherein for each monomer having Formula V, Z1 or Z2 is H and the other of Z1 and Z2 is C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl or substituted C2-C6 alkynyl. 3. The oligomeric compound of claim 2 wherein the other of Z1 and Z2 is CH2F, CHF2 or CF3. 4. The oligomeric compound of claim 2 wherein the other of Z1 and Z2 is C1-C6 alkyl or substituted C1-C6 alkyl. 5. The oligomeric compound of claim 2 wherein the other of Z1 and Z2 is CH3. 6. The oligomeric compound of claim 1 wherein for each monomer having Formula V, Q1 and Q2 are each, independently, H, C1-C6 alkyl or substituted C1-C6 alkyl wherein at least one of Q1 and Q2 is other than H. 7. The oligomeric compound of claim 1 wherein for each monomer having Formula V, one of Q1 and Q2 is H and the other of Q1 and Q2 is C1-C6 alkyl or substituted C1-C6 alkyl. 8. The oligomeric compound of claim 7 wherein the other of Q1 and Q2 is CH3. 9. The oligomeric compound of claim 1 wherein for each monomer having Formula V, one of Q1 and Q2 is H and the other of Q1 and Q2 is CH2F, CHF2 or CF3. 10. The oligomeric compound of claim 1 wherein for each monomer having Formula V, Q1 and Q2 are each CH3. 11. The oligomeric compound of claim 1 wherein for each monomer having Formula V, Q1 and Q2 together are methylene (═CH2). 12. The oligomeric compound of claim 1 wherein for each monomer having Formula V, one of Q1 and Q2 is H, the other of Q1 and Q2 is CH3, one of Z1 or Z2 is H and the other of Z1 and Z2 is CH3. 13. The oligomeric compound of claim 1 wherein for each monomer having Formula V, Bx is uracil, thymine, cytosine, 5-methylcytosine, 2,6-diaminopurine, adenine or guanine. 14. The oligomeric compound of claim 1 wherein each internucleoside linking group is, independently, a phosphodiester or phosphorothioate. 15. The oligomeric compound of claim 1 wherein each internucleoside linking group is a phosphorothioate. 16. The oligomeric compound of claim 1 wherein for each monomer having Formula V, Z2 and Q2 are each H. 17. The oligomeric compound of claim 16 wherein Z1 and Q1 are each CH3 for each monomer having Formula V. 18. The oligomeric compound of claim 1 wherein Z2 and Q1 are each H for each monomer having Formula V. 19. The oligomeric compound of claim 18 wherein Z1 and Q2 are each CH3 for each monomer having Formula V. 20. The oligomeric compound of claim 1 wherein Z1 and Q2 are each H for each monomer having Formula V. 21. The oligomeric compound of claim 20 wherein Z2 and Q1 are each CH3 for each monomer having Formula V. 22. The oligomeric compound of claim 1 wherein Z1 and Q1 are each H for each monomer having Formula V. 23. The oligomeric compound of claim 22 wherein Z2 and Q2 are each CH3 for each monomer having Formula V. 24. The oligomeric compound of claim 1 comprising from about 8 to about 20 monomeric subunits. 25. The oligomeric compound of claim 1 comprising from about 10 to about 16 monomeric subunits. 26. The oligomeric compound of claim 1 comprising from about 10 to about 14 monomeric subunits.
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