Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Sting-agonist compound

A compound and solvate technology, applied in the field of STING agonist compounds, can solve the problems of unreported STING agonist compounds, and achieve the effect of inhibiting progress and inhibiting recurrence

Pending Publication Date: 2021-05-28
ONO PHARMA CO LTD
View PDF35 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no STING agonist compound having a structure similar to the compound of the present invention has been reported

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
  • Sting-agonist compound
  • Sting-agonist compound
  • Sting-agonist compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0486] Example 1: 2-amino-5-(3-amino-7-(1H-pyrazol-4-yl)isoxazolo[4,5-c]pyridin-4-yl)-4- Methyl fluorobenzoate

[0487]

[0488] Trifluoroacetic acid (4.0 mL) was added to a dichloromethane solution (4.0 mL) in which the compound produced in Reference Example 13 (388 mg) was dissolved, and the mixture was stirred at 40°C for 5 hr. To the reaction solution was added saturated sodium bicarbonate, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and concentrated. The residue thus obtained was purified by silica gel column chromatography (Hi-flash SI) (hexane:ethyl acetate=90:10 to 0:100) to obtain the present compound (19.6 mg) having the following physical property values.

[0489] LCMS retention time (min): 0.59;

[0490] MS (ESI, Pos.): 369 (M+H) + ;

[0491] 1 H-NMR (CD 3 OD): δ8.86(s,1H),8.34(s,2H),8.05(d,J=8.5Hz,1H),6.66(d,J=12.5Hz,1H),3,85(s,3H ).

Embodiment 2

[0492] Example 2: 4-(4-amino-2-fluoro-5-methoxyphenyl)-7-(1H-pyrazol-4-yl)isoxazolo[4,5-c] Pyridin-3-amine hydrochloride

[0493] Under nitrogen atmosphere, 5-fluoro-2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (CAS No.1326283-60-6) (224 mg), bis[tri-tert-butylphosphine] palladium (65.9 mg) and 2 mol / L tripotassium phosphate aqueous solution (1.1 mL) were added to the compound dissolved in Reference Example 6 (235 mg) in 1,4-dioxane (7.1 mL), and the mixture was stirred at 110° C. for 3 hours. The reaction solution was directly purified by silica gel column chromatography (Hi-flash SI) (hexane:ethyl acetate=100:0 to 0:100) to give 4-(4-amino-2-fluoro-5-methoxyphenyl )-7-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)isoxazolo[4,5-c]pyridin-3-amine (108 mg).

[0494] Hydrochloric acid (10% methanol solution, 2.0 mL) was added to a THF solution (2.2 mL) in which the compound (108 mg) was dissolved, and the mixture was stirred at room temperature for 2 hr...

Embodiment 3

[0498] Example 3: 1-(2-amino-5-(3-amino-7-(1H-pyrazol-4-yl)isoxazolo[4,5-c]pyridine-4- Base)-4-fluorophenyl)ethan-1-one

[0499]Under a nitrogen atmosphere, borate (10.7 g), butyl bis-1-adamantylphosphine (984 mg), palladium acetate (308 mg), potassium iodide (456 mg) and 2 mol / L tripotassium phosphate aqueous solution (28 mL) was added to 1-methyl-2-pyrrolidone solution (hereinafter, abbreviated as NMP) (100 mL) in which the compound (10.0 g) produced in Reference Example 6 was dissolved, and it was The mixture was stirred at 50 to 60°C for 45 hours. After the reaction solution was cooled, insoluble matter was removed by filtration while washing with NMP. To the obtained filtrate was added tap water (240 mL) little by little, the mixture was stirred for 40 minutes, and the solid precipitated therein was collected by filtration. The solid obtained was slurry washed sequentially with acetonitrile (80 mL, twice) and methyl tert-butyl ether (80 mL, twice), then filtered an...

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 addresses the problem of providing a pharmaceutical product containing, as an active ingredient, a compound having agonistic activity to STING. As a result of extensive investigations, the inventors of the present invention have discovered, as substances capable of solving the problem, compounds represented by general formula (I-1) [all of the symbols in the formula are as described in the description] and having agonistic activity to STING, thereby arriving at the present invention. The compounds represented by general formula (I-1) according to the present invention have agonistic activity to STING, and can thus be used as active ingredients of agents for treating, suppressing the progress of, and / or suppressing the recurrence of cancer or infectious diseases.

Description

[technical field] [0001] The present invention relates to compounds represented by general formula (I): [0002] [0003] [wherein, all symbols have the same meanings as described below. ], their N-oxides, their prodrugs, their pharmaceutically acceptable salts or their solvates, and compounds represented by the general formula (I-1): [0004] [0005] [wherein, all symbols have the same meanings as described below. ], N-oxides thereof, pharmaceutically acceptable salts thereof, or solvates thereof (hereinafter, these compounds may be described as "compounds of the present invention") and compounds containing any of these compounds as an active ingredient Pharmaceutical composition, and pharmaceutical use thereof. [Background technique] [0006] STING (Stimulation of Interferon Genes) is known to be an endoplasmic reticulum-localized tetraspanin and is involved in innate immunity. When foreign double-stranded DNA appears in the cytoplasm due to infection or the lik...

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): C07D498/04A61P31/00A61P35/00A61P35/02C07D513/04A61K31/437A61K45/00
CPCA61P35/00A61P35/02C07D498/04C07D513/04C07F9/6561A61K31/661A61K45/06A61P31/00A61K31/437C07F9/062
Inventor 花田良辅小久保雅也黑野昌邦幸田健一萩谷洋
Owner ONO PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com