Back to results
US 8,088,746 B2Granted
Bis-modified bicyclic nucleic acid analogs
AssigneeIsis Pharmaceuticals, Inc.
InventorsPunit P. Seth, Eric E. Swayze
Life of this patent
Estimating the term…
Abstract
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.
Claims26
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;
- and
- the sum of j and r is at least 1.
15 more elements
Dependencies are inferred from the claim text.