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US 8,278,426 B2Granted
Carbocyclic bicyclic nucleic acid analogs
AssigneeIsis Pharmaceuticals, Inc.
InventorsPunit P. Seth, Eric E. Swayze
Life of this patent
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Abstract
Provided herein are saturated and unsaturated carbocyclic bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using these oligomeric compounds. The saturated and unsaturated carbocyclic bicyclic nucleosides are useful for enhancing properties of oligomeric compounds including nuclease resistance.
Claims55
A bicyclic nucleoside having Formula I:
- wherein:
- Bx is a heterocyclic base moiety;
- one of T1 and T2 is H or a hydroxyl protecting group and the other of T1 and T2 is H, a hydroxyl protecting group or a reactive phosphorus group;
- Q is C(q1)(q2)C(q3)(q4), C(q1)=C(q3), C[═C(q1)(q2)]-C(q3)(q4) or C(q1)(q2)-C [═(q3)(q4)];
- q1, q2, q3 and q4 are each, independently, H, halogen, C1-C12 alkyl, substituted C1-C12 alkyl, C2-C12 alkenyl, substituted C2-C12 alkenyl, C2-C12 alkynyl, substituted C2-C12 alkynyl, C1-C12 alkoxy, substituted C1-C12 alkoxy, OJ1, SJ1, SOJ1, SO2J1, NJ1J2, N3, CN, C(═O)OJ1, C(═O)NJ1J2, C(═O)J1, O—C(═O)NJ1J2, N(H)C(═NH)NJ1J2, N(H)C(═O)NJ1J2 or N(H)C(═S)NJ1J2;
- wherein each substituted group is, independently, mono or poly substituted with substituent groups independently selected from halogen, OJ1, SJ1, NJ1J2, N3, CN, C(═O)OJ1, C(═O)NJ1J2, C(═O)J1, O—C(═O)NJ1J2, N(H)C(═O)NJ1J2 or N(H)C(═S)NJ1J2;
- each J1 and J2 is, independently, H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 aminoalkyl or a protecting group;
- and
- wherein when Q is C(q1)(q2)C(q3)(q4) and one of q3 or q4 is CH3 then at least one of the other of q3 or q4 or one of q1 and q2 is other than H.
6 more elements
An oligomeric compound comprising at least one bicyclic nucleoside having Formula IV:
- wherein independently for each bicyclic nucleoside having Formula IV:
- Bx is a heterocyclic base moiety;
- one of T3 and T4 is an internucleoside linking group linking the bicyclic nucleoside having Formula IV to the oligomeric compound and the other of T3 and T4 is H, a hydroxyl protecting group, a linked conjugate group, a 5′ or 3′-terminal group or an internucleoside linking group linking the bicyclic nucleoside having Formula IV to the oligomeric compound;
- Q is C(q1)(q2)C(q3)(q4), C(q1)=C(q3), C[═C(q1)(q2)]-C(q3)(q4) or C(q1)(q2) -C[═C(q3)(q4)];
- q1, q2, q3 and q4 are each, independently, H, halogen, C1-C12 alkyl, substituted C1-C12 alkyl, C2-C12 alkenyl, substituted C2-C12 alkenyl, C2-C12 alkynyl, substituted C2-C12 alkynyl, C1-C12 alkoxy, substituted C1-C12 alkoxy, OJ1, SJ1, SOJ1, SO2J1, NJ1J2, N3, CN, C(═O)OJ1, C(═O)NJ1J2, C(═O)J1, O—C(═O)NJ1J2, N(H)C(═NH)NJ1J2, N(H)C(═O)NJ1J2 or N(H)C(═S)NJ1J2;
- wherein each substituted group is, independently, mono or poly substituted with substituent groups independently selected from halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, OJ1, SJ1, NJ1J2, N3, CN, C(═O)OJ1, C(═O)NJ1J2, C(═O)J1, O—C (═O)NJ1J2, N(H)C(═O)NJ1J2 or N(H)C(═S)NJ1J2;
- each J1 and J2 is, independently, H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 aminoalkyl or a protecting group;
- and
- wherein when Q is C(q1)(q2)C(q3)(q4) and one of q3 or q4 is CH3 then at least one of the other of q3 or q4 or one of q1 and q2 is other than H.
6 more elements
Dependencies are inferred from the claim text.