Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
1. An oligomeric compound comprising at the 5′-position a moiety having one of the formulas:
wherein:
T 1 is a phosphorus moiety having the formula:
wherein:
R a and R c are each, independently, OH, SH, protected hydroxyl, protected thiol, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, substituted C 1 -C 6 alkoxy, protected amino or substituted amino;
R b is O or S;
Q 1 and Q 2 are each, independently, H, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, or substituted C 1 -C 6 alkoxy;
each substituted group comprises one or more optionally protected substituent groups independently selected from halogen, OJ 1 , N(J 1 )(J 2 ), =NJ 1 , SJ 1 , N 3 , CN, OC(═X 2 )J 1 , OC(═X 2 )N(J 1 )(J 2 ) and C(═X 2 )N(J 1 )(J 2 );
X 2 is O, S or NJ 3 ; and
J 1 , J 2 and J 3 are each, independently, H or C 1 -C 6 alkyl.
2. The oligomeric compound of claim 1 , wherein Q 1 and Q 2 are each, independently, H or C 1 -C 6 alkyl.
3. The oligomeric compound of claim 1 , wherein Q 1 and Q 2 are each H.
4. The oligomeric compound of claim 1 , wherein R a and R c are each, independently, OCH 3 , OCH 2 CH 3 , or OCH(CH 3 ) 2 .
5. The oligomeric compound of claim 1 , wherein R a and R c are each, independently, OH or OCH 3 .
6. The oligomeric compound of claim 4 , wherein R b is O.
7. The oligomeric compound of claim 5 , wherein R b is O.
8. The oligomeric compound of claim 1 , wherein the moiety at the 5′-position has the formula:
9. The oligomeric compound of claim 1 , wherein the moiety at the 5′-position has the formula: