Oligonucleotide and artificial nucleoside having guanidine bridge

Patent metadata

Field	Value
Publication number	US-10377789-B2
Application number	US-201314428646-A
Country	US
Kind code	B2
Filing date	Sep 19, 2013
Priority date	Sep 21, 2012
Publication date	Aug 13, 2019
Grant date	Aug 13, 2019

Abstract

A compound represented by formula I or II below or a salt thereof:

wherein B 1 represents a purin-9-yl group or a 2-oxo-1,2-dihydropyrimidin-1-yl group that has any one or more substituents selected from the group consisting of a hydroxyl group, a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, an amino group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom.

First claim

The invention claimed is:

1. A compound represented by formula I or II below or a salt thereof:

wherein B 1 represents:
a purin-9-yl group;
a 2-oxo-1,2-dihydropyrimidin-1-yl group;
a purin-9-yl group that has any one or more substituents selected from the group consisting of a hydroxyl group, a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, an amino group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom;
a 2-oxo-1,2-dihydropyrimidin-1-yl group that has any one or more substituents selected from the group consisting of a hydroxyl group, a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, an amino group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom;

R 1 , R 12 , and R 13 each independently represent a hydrogen atom, a C 1 to C 7 alkyl group that is a straight chain, a branched chain or up to a C 7 ring, a protecting group for an amino group, or

and
R 2 and R 3 each independently represent
a hydrogen atom,
a protecting group for a hydroxyl group in nucleic acid synthesis,
a C 1 to C 7 alkyl group that is a straight chain, a branched chain or up to a C 7 ring,
a C 2 to C 7 alkenyl group that is a straight chain, a branched chain or up to a C 7 ring,
a C 6 to C 12 aryl group,
a C 6 to C 12 aryl group that has any one or more substituents selected from the group consisting of a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom,
a C 6 to C 12 aryl group that has any one or more substituents selected from the group consisting of a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom,
an aralkyl group having a C 6 to C 12 aryl moiety,
an aralkyl group having a C 6 to C 12 aryl moiety that has any one or more substituents selected from the group consisting of a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom,
an aralkyl group having a C 6 to C 12 aryl moiety,
an aralkyl group having a C 6 to C 12 aryl moiety that has any one or more substituents selected from the group consisting of a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkylthio group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom,
an acyl group that has any one or more substituents selected from the group consisting of a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, a C 1 to C 6 linear alkylthio group, a C 1 to C 6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom,
a silyl group that has three substituents selected from the group consisting of a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 6 linear alkyl group, a C 1 to C 6 linear alkoxy group, and an amino group protected by a protecting group in nucleic acid synthesis,
a phosphate group,
a phosphate group that has any one or more substituents selected from the group consisting of a C 1 to C 6 linear alkyl group, and a C 1 to C 6 linear alkoxy group,
a phosphate group protected by a protecting group in nucleic acid synthesis, or
—P(R 4 )R 5 , wherein R 4 and R 5 each independently represent a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C 1 to C 5 alkoxy group, a C 1 to C 6 cyanoalkoxy group, or a dialkylamino group substituted with a two C 1 to C 6 alkyl groups,

wherein the protecting group in nucleic acid synthesis is a C 1 to C 6 alkyl group; a C 1 to C 6 alkenyl group; an acyl group; a tetrahydropyranyl group or a tetrahydrothiopyranyl group; a tetrahydrofuranyl group or a tetrahydrothiofuranyl group; a methyl group substituted with a C 1 to C 6 alkoxy group; a methyl group substituted with a C 1 to C 6 alkoxy group substituted with a C 1 to C 6 alkoxy group; a methyl group substituted with a C 1 to C 6 alkoxy group substituted with a halogen atom; an ethyl group substituted with a C 1 to C 6 alkoxy group; an ethyl group substituted with a halogen atom; a methyl group substituted with one to three aryl groups; a methyl group substituted with one to three aryl groups substituted with at least one substituent selected from the group consisting of a C 1 to C 6 alkyl group, a C 1 to C 6 alkoxy group, a halogen atom, and a cyano group; a carbonyl group substituted with a C 1 to C 6 alkoxy group; an aryl group substituted with at least one substituents selected from the group consisting of a halogen atom, a C 1 to C 6 alkoxy group, and a nitro group; a carbonyl group substituted with a C 1 to C 6 alkoxy group substituted with at least one substituent selected from the group consisting of a halogen atom and a silyl group substituted with three C 1 to C 6 alkyl groups; an alkenyloxycarbonyl group; or an aralkyloxycarbonyl group substituted with an aryl group substituted with at least one substituent selected from the group consisting of a C 1 to C 6 alkoxy group and a nitro group;
wherein the protecting group for a hydroxyl group in nucleic acid synthesis is an aliphatic acyl group; an aromatic acyl group; a methyl group substituted with one to three aryl groups; a methyl group substituted with one to three aryl groups substituted with at least one substituent selected from the group consisting of a C 1 to C 6 alkyl group, a C 1 to C 6 alkoxy group, a halogen atom, a cyano group and a trialkyl substituted silyl group; and
wherein the protecting group for an amino group is an acyl group, a benzoyl group, a tert-butoxycarbonyl group, or a 9-fluorenylmethyloxycarbonyl group;
and with the proviso that substituents specified in all chemical structures by each of the terms —OH (hydroxyl group), mercapto group (—SH), a C 1 to C 6 linear alkylamino group, a phosphate group, and

Assignees

• Univ Osaka

Inventors

• Obika Satoshi
• Kotobuki Yutaro
• Waki Reiko

Classifications

• C07H23/00

  Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) · CPC title

• C07H21/04

  with deoxyribosyl as saccharide radical · CPC title

• C07H19/06 Primary

  Pyrimidine radicals · CPC title

• C07H19/10 Primary

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title

• C07H21/00

  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 title