Unlock instant, AI-driven research and patent intelligence for your innovation.

Nucleic acid complex

A complex, nucleic acid technology, applied in the direction of sugar derivatives, drug combinations, genetic material components, etc., can solve the problem of specifically inhibiting the expression of APCS that has not yet been reported.

Pending Publication Date: 2021-08-20
KYOWA HAKKO KIRIN CO LTD
View PDF17 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] It is expected that amyloid-related diseases can be prevented or treated by specifically inhibiting the expression of APCS, but no pharmaceuticals that specifically inhibit the expression of APCS have been reported so far.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Nucleic acid complex
  • Nucleic acid complex
  • Nucleic acid complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0917] Hereinafter, the present invention will be specifically described using reference examples, working examples, and test examples. However, the present invention is not limited to these Examples and Test Examples. It should be noted that the proton NMR spectra ( 1 H NMR) is measured at 270 MHz, 300 MHz, or 400 MHz, and the exchanged protons may not be clearly observed depending on the compound and measurement conditions. In addition, as an expression of the multiplicity of a signal, a commonly used expression is used, and br means broad, and represents an apparently wide signal.

[0918] The following conditions were used for the UPLC analysis.

[0919] Mobile phase A: aqueous solution containing 0.1% formic acid, B: acetonitrile solution

[0920] Gradient: 10%-90% linear gradient of mobile phase B (3 minutes)

[0921] Column: ACQUITY UPLC BEH C18 (1.7 μm, inner diameter 2.1×50 mm) manufactured by Waters Corporation

[0922] Flow rate: 0.8mL / min

[0923] PDA detecti...

reference example 1

[0956] [chemical formula 123]

[0957]

[0958] Synthesis of compound RE1-2

[0959] Reference Example 1 Process 1

[0960] Compound RE1-1 (0.8755 g, 1.9567 mmol) synthesized by the method described in Journal of American Chemical Society, vol. 136, pp. 16958-16961, 2014 was dissolved in tetrahydrofuran (10 mL), Add 1,3-dicyclohexylcarbodiimide (DCC, 0.4247g, 2.0584mmol) and N-hydroxysuccinimide (0.2412g, 2.0958mmol) and stir overnight at room temperature. The solid precipitated from the reaction mixture was removed, and the solvent was distilled off under reduced pressure. The resulting mixture was dissolved in N,N'-dimethylformamide (DMF), 2-aminoethylmaleimide bromate (0.6479 g, 2.5491 mmol) and diisopropylethylamine were added (1.7mL, 9.7835mmol), then stirred overnight at room temperature. Under reduced pressure, the solvent in the reaction solution was distilled off, and it was eluted by reversed-phase column chromatography (water / methanol=80 / 20), thereby obtainin...

reference example 2

[0972] [chemical formula 124]

[0973]

[0974] Reference Example 2 Process 1

[0975] ((2R,3R)-1,3-Dihydroxybutan-2-yl)(9H-fluoren-9-yl)methyl carbamate (compound RE2-1, manufactured by Chem-Impex International, Inc., 1.50 g, 4.58mmol) was dissolved in pyridine (20mL), and 4,4'-dimethoxytrityl chloride (manufactured by Tokyo Chemical Industry Co., Ltd., 1.71g, 5.04mmol) was added under ice-cooling, followed by stirring at room temperature 2 hours. The reaction solution was ice-cooled, 10% citric acid aqueous solution was added, extracted with ethyl acetate, the organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate=90 / 10) to obtain compound RE2-2 (1.07 g, yield 37%).

[0976] ESI-MS m / z:630(M+H) +

[0977] Reference Example 2 Process 2

[0978]The compound RE2-2 (1.07g, 1.699mmol) synthesized ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides a nucleic acid complex represented by formula 1. Formula 1: (In formula 1, X is a double-stranded nucleic acid that comprises a sense strand and an antisense strand and that includes a duplex region of at least 11 base pairs; the double-stranded nucleic acid is complementary with any of the target APCS mRNA sequences listed in Tables 1-1 to 1-13 in an oligonucleotide strand having a strand length of 17-30 nucleotides in the antisense strand, and the 3' end or 5' end of the sense strand bonds to S3; L1 and L2 each independently represent a sugar ligand; S1, S2, and S3 each independently represent a linker.).

Description

technical field [0001] The present invention relates to a nucleic acid complex, a pharmaceutical composition containing the nucleic acid complex, and the like. Background technique [0002] As nucleic acid drugs, aptamers, antisense nucleic acids, Decoy nucleic acids, ribozymes, siRNA, miRNA, and antimiRNA are known. Due to their high versatility (capable of controlling all genes in cells), nucleic acid drugs are expected to be clinically applied to various diseases that are currently considered difficult to treat. [0003] In addition, nucleic acid drugs are highly anticipated as next-generation drugs following antibodies and low-molecular-weight drugs due to their high intracellular targeting selectivity and high activity. [0004] However, as a problem of nucleic acid drugs, it is difficult to deliver them to target tissues. [0005] As one of the effective delivery methods of nucleic acid drugs in vivo, the use of nucleic acid complexes (conjugates) of targeting compou...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7105A61K31/713A61K48/00A61P25/28C07H15/04A61K47/54C12N15/113
CPCA61P25/28C12N15/113A61K47/549C07H21/02C12N2310/14C12N2310/3515C12N15/87C07H15/04A61K31/7105A61K31/713A61K47/54A61K48/00C12N2310/11C12N2310/351C07H5/06
Inventor 岩井宏徒今枝隆有山博之村上拓也
Owner KYOWA HAKKO KIRIN CO LTD