Oligonucleoside linkages containing adjacent nitrogen atoms

• US 6,214,551 B1
• Filed: 07/27/1998
• Issued: 04/10/2001
• Est. Priority Date: 07/27/1990
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Sanghvi, Yogesh S., Cook, Phillip Dan
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US09/123,572
• Time in Patent Office: 988 Days
• Field of Search: 435/6, 536/22.1, 536/23.1, 536/24.3, 536/25.3
• US Class Current: 435/6.14
• 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: A61K 47/605 the macromolecule containing phosphorus in the main chain, e.g. poly-phosphazene
• 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 method of assaying a sequence-specific nucleic acid, comprising contacting a test solution containing said nucleic acid with a compound having structure:

wherein;

L₁-L₂-L₃-L₄ is 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 or substituted alkyl having 1 to about 10 carbon atoms;

alkenyl or substituted alkenyl 2 to about 10 carbon atoms;

alkynyl or substituted alkynyl having 2 to about 10 carbon atoms;

alkaryl, substituted alkaryl, aralkyl, or substituted aralkyl having 7 to about 14 carbon atoms;

alicyclic;

heterocyclic;

a reporter molecule;

B_x is a nucleosidic base;

Q is O, S, CH₂, CHF or CF₂;

n is an integer greater than 0;

X is H, OH, C₁ to C₁₀ lower alkyl, substituted lower alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF₃, OCF₃, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH₃, SO₂CH₃,ONO₂, NO₂, N₃, NH₂, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino or substituted silyl.

2. The method of claim 1 wherein L₁-L₂-L₃-L₄ is CH₂—

NR₁ NR₂—

CH₂.

3. The method of claim 1 wherein L₁-L₂-L₃-L₄ is NR₁—

NR₂—

CH ₂—

CH₂.

4. The method of claim 1 wherein L₁-L₂-L₃-L₄ is CH₂—

CH₂—

NR 1—

NR₂.

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

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

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

C₂ to C₁₀ straight or branched chain lower alkynyl or substituted lower alkynyl;

or C₇ to C₁₄ alkaryl or aralkyl.

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

or a ¹⁴C containing C₇ to C₁₄ alkaryl or aralkyl.

8. The method of claim 1 wherein at least one of R₁ and R₂ is a reporter molecule.

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

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