Modified nucleic acid

• US 9,725,474 B2
• Filed: 10/30/2013
• Issued: 08/08/2017
• Est. Priority Date: 10/31/2012
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Murata, Shumpei, Masada, Shinichi, Miyamoto, Naoki, Umemoto, Tadashi
• Primary Examiner(s): Ward, Paul V
• Application Number:
  US14/439,460
• Publication Number:
  US 20160016983A1
• Time in Patent Office: 1,378 Days
• CPC Class Codes: C07D 239/54 as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine
• CPC Class Codes: C07F 9/6512 having the nitrogen atoms in positions 1 and 3
• CPC Class Codes: C07F 9/65583 each of the hetero rings containing nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/65586 at least one of the hetero rings does not contain nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/65616 containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
• 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
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical

Abstract

Provided is an oligonucleic acid analog which contains, as at least one structural unit thereof, a modified nucleic acid monomer compound which is a ring-open nucleoside having a cleaved carbon-carbon bond between the 2′ and 3′ positions and a substituent hydroxymethyl group at the 4′ position. When used as siRNA, the oligonucleic acid analog exhibits superior biological stability and target gene expression inhibiting activity. The oligonucleic acid analog can be used in antisense methods, ribozyme methods, and decoy methods, etc., can be used as a nucleic acid aptamer, and can also be used as a nucleic acid probe or molecular beacon, etc., or in genetic diagnostics, etc.

Claims

1. A compound represented by the following formula (I):

5. The compound according to claim 1 or 3, wherein B is an adenine-derived group or a guanine-derived group, or a salt thereof.

6. The compound according to claim 1 or 3, wherein R¹ is a C_1-6 alkyl group, or a salt thereof.

2. An oligonucleic acid analog comprising one or more partial structures each represented by the following formula (II):

7. The oligonucleic acid analog according to claim 2 or 4, wherein B is an adenine-derived group or a guanine-derived group, or a salt thereof.

8. The oligonucleic acid analog according to claim 2 or 4, wherein R¹ is a C_1-6 alkyl group, or a salt thereof.

3. A compound represented by the following formula (III):

4. An oligonucleic acid analog comprising one or more partial structures each represented by the following formula (IV):