Oligonucleoside linkages containing adjacent nitrogen atoms

• US 5,792,844 A
• Filed: 10/03/1994
• Issued: 08/11/1998
• Est. Priority Date: 07/27/1990
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Cook, Phillip Dan, Sanghvi, Yogesh S.
• Primary Examiner(s): Low, Christopher S. F.
• Application Number:
  US08/317,289
• Time in Patent Office: 1,408 Days
• Field of Search: 536/23.1, 536/24.1, 536/24.5, 514/44, 435/6, 935/2, 935/3, 935/8
• US Class Current: 536/23.1
• 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:

##STR7## wherein;

L₁ --L₂ --L₃ --L₄, respectively, are CH₂ --NR₁ --NR₂ --CH₂, CH₂ --CH₂ --NR₁ --NR₂, or NR₁ --NR₂ --CH₂ --CH₂ ;

R₁ and R₂ are the same or different and are H;

alkyl having 1 to 10 carbon atoms;

alkenyl having 2 to 10 carbon atoms;

alkynyl having 2 to 10 carbon atoms;

aralkyl having 7 to 14 carbon atoms;

alicyclic;

heterocyclic;

a reporter molecule;

or an RNA cleaving group;

B_x is a nucleosidic base;

Q is O, S, CH₂, CHF or CF₂ ;

n is an integer greater than O;

X is H, OH, C₁, to C₁₀ lower alkyl, aralkyl, 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, heterocycloalkyl, heterocycloaralkyl, aminoalkylamino, polyalkylamino, substituted silyl, or an RNA cleaving group "wherein said compound exhibits nuclease resistance and base pair binding specificity".

2. The compound of claim 1 wherein L₁ --L₂ --L₃ --L₄ is CH₂ --NR₁ --NR₂ --CH₂.

3. The compound of claim 1 wherein L₁ --L₂ --L₃ --L₄ is NR₁ --NR₂ --CH₂ --CH₂.

4. The compound of claim 1 wherein at least one of R₁ and R₂ is C₁ to C₁₀ alkyl.

5. The compound of claim 1 wherein at least one of R₁ and R₂ is H.

6. The compound of claim 1 wherein at least one of R₁ and R₂ is C₁ to C₁₀ straight chain lower alkyl or C₃ to C₁₀ branched chain lower alkyl;

C₂ to C₁₀ straight chain lower alkenyl or C₃ to C₁₀ branched chain lower alkenyl;

C₂ to C₁₀ straight chain lower alkynyl or C₃ to C₁₀ branched chain lower alkynyl.

7. The compound of claim 1 wherein at least one of R₁ and R₂ is a ¹⁴ C containing lower alkyl, lower alkenyl or lower alkynyl;

or a ¹⁴ C containing C₇ to C₁₄ aralkyl.

8. The compound of claim 1 wherein at least one of R₁ and R₂ is a reporter molecule or an RNA cleaving group.

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

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