Bicyclonucleoside and oligonucleotide analogues

• US 6,268,490 B1
• Filed: 09/07/1999
• Issued: 07/31/2001
• Est. Priority Date: 03/07/1997
• Status: Expired

• Current Assignee: Exiqon A/S (Qiagen NV), Roche Innovation Center Copenhagen A/S (Roche Holding AG)
• Original Assignee: Takeshi Imanishi
• Inventors: Imanishi, Takeshi, Obika, Satoshi
• Primary Examiner(s): Killos, Paul J.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US09/380,638
• Time in Patent Office: 693 Days
• Field of Search: 536/23.1, 536/26.7, 536/26.8, 536/26.9, 536/27.21, 536/28.4
• US Class Current: 536/23.1
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 493/08 Bridged systems
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• 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

An oligo- or polynucleotide analogue having one or more structures of the general formula

where B is a pyrimidine or purine nucleic acid base, or an analogue thereof,

is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

Claims

1. A nucleoside analogue of the following formula (I)

where B is a pyrimidine or purine nucleic acid base, and X and Y are identical or different, and each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group, an aryl group, an acyl group, or a silyl group, or an amidite derivative thereof.

2. A nucleoside analogue as claimed in claim 1, wherein X and Y each represents a hydrogen atom.

3. A mononucleoside amidite derivative as claimed in claim 1, wherein X is 4,4-dimethoxytrityl (DMTr), and Y is a 2-cyanoethoxy(diisopropylamino)phosphano group.

6. The nucleoside analogue according to claim 1 wherein the amidite derivative is a phosphoramidite.

4. An oligonucleotide or polynucleotide analogue having one or more structures or the formula (Ia)

where B is a pyrimidine or purine nucleic acid base.

7. The nucleoside analogue according to claim 4 wherein the amidite derivative is a phosphoramidite.

5. An oligonucleotide or polynucleotide analogue of the formula (II)

where B¹ and B are identical or different, and each represents a pyrimidine or purine nucleic acid base, R is a hydrogen atom, a hydroxyl group, a halogen atom, or an alkoxy group,

W¹ and W² are identical or different, and each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group, an aryl group, an acyl group, a silyl group, a phosphoric acid residue, a naturally occurring nucleoside or a synthetic nucleoside bound via a phosphodiester bond, or an oligonucleotide or polynucleotide containing the nucleoside, n¹ or n² are identical or different, and each denotes an integer of 0 to 50, provided that n¹ and n² are not both zero, and that not all of the n² are zero at the same time, n³ denotes an integer of 1 to 50, provided that when n¹ and/or n² are or is 2 or more, B¹ and B need not be identical, and R need not be identical.

8. The nucleoside analogue according to claim 5 wherein the amidite derivative is a phosphoramidite.