Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms

• US 5,489,677 A
• Filed: 03/31/1993
• Issued: 02/06/1996
• Est. Priority Date: 07/27/1990
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Cook, Phillip D., Sanghvi, Yogesh S.
• Primary Examiner(s): Fleisher, Mindy
• Assistant Examiner(s): CARTER, PHILIP
• Application Number:
  US08/040,526
• Time in Patent Office: 1,042 Days
• Field of Search: 536/22.1, 536/24.1, 536/25.3, 536/24.5, 536/24.3, 536/24.31, 536/24.32
• US Class Current: 536/22.1
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds contain a selected nucleoside sequence wherein the nucleosides are covalently bound through linking groups that contain adjacent nitrogen atoms.

Claims

1. A compound having structure:

##STR8## wherein;

L₁ -L₂ -L₃ -L₄ is CH₂ --O--NR--CH₂, CH₂ --NR--O--CH₂, O--NR--CH₂ --CH₂, CH₂ --CH₂ --NR--O, CH₂ --CH₂ --O--NR, or NR--O--CH₂ --CH₂ ;

R is H, alkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, or alkynyl having 2 to about 10 carbon atoms;

B_x is a nucleosidic base;

Q is O, S, CH₂, CHF or CF₂ ;

n is 1-50;

X is H, OH, alkyl, F, Cl, Br, CN, CF₃, OCF₃, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH₃, SO₂ CH₃, ONO₂, NO₂, N₃, NH₂, aminoalkylamino, polyalkylamino or substituted silyl, wherein each said alkyl has from 1 to about 10 carbon atoms and each said alkenyl has from 2 to about 10 carbon atoms.

2. The compound of claim 1 wherein L₁ -L₂ -L₃ -L₄ is CH₂ --O--NR--CH₂.

3. The compound of claim 1 wherein L₁ -L₂ -L₃ -L₄ is CH₂ --NR--O--CH₂.

4. The compound of claim 1 wherein L₁ -L₂ -L₃ -L₄ is 0--NR--CH₂ --CH₂.

5. The compound of claim 1 wherein L₁ -L₂ -L₃ -L₄ is NR--O--CH₂ --CH₂.

6. The compound of claim 1 wherein R is C₁ to C₁₀ alkyl.

7. The compound of claim 1 wherein R is methyl.

8. The compound of claim 1 wherein R is H.

9. The compound of claim 1 wherein Q is O.

10. The compound of claim 1 wherein X is H or OH.

11. The compound of claim 1 wherein R is alkyl, alkenyl or alkynyl.

12. The compound of claim 1 wherein R is alkyl.

13. The compound of claim 1 wherein X is F.

14. The compound of claim 1 wherein X is O-alkyl.

15. The compound of claim 1 wherein X is O-alkyl having 1 to 4 carbon atoms.

16. The compound of claim 1 wherein X is O-methyl.