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

Substituted naphthyridine-2-ketone compound, preparation method, application and pharmaceutical composition

A compound and pharmacy technology, applied in uses and pharmaceutical compositions, substituted naphthyridin-2-one compounds, in the field of preparation methods, can solve the problems of large toxic and side effects, low therapeutic effect and the like

Active Publication Date: 2015-03-18
NEW FOUNDER HLDG DEV LLC +2
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing PI3-Kα inhibitors have the disadvantages of high toxicity and side effects and low therapeutic effect in clinical trials. Therefore, it is urgent to develop new PI3-Kα inhibitors, which can be used as cancer therapeutic drugs in the field of cancer treatment

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
  • Substituted naphthyridine-2-ketone compound, preparation method, application and pharmaceutical composition
  • Substituted naphthyridine-2-ketone compound, preparation method, application and pharmaceutical composition
  • Substituted naphthyridine-2-ketone compound, preparation method, application and pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0185] (2) The preparation method of the compound shown in formula I:

[0186] The present invention secondly provides a kind of preparation method of the compound shown in formula I, it comprises:

[0187] Make the compound shown in formula A and the compound shown in formula B react as follows under the presence of palladium catalyst, thereby obtain the compound shown in formula I:

[0188]

[0189] Among them, R 1 and R 3 as defined in claim 1; X is halogen, preferably bromine; and R 8 for or

[0190] Preferably, the palladium catalyst is bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride.

[0191] Preferably, the compound shown in formula A is prepared by the following method:

[0192] Make the compound shown in formula L and N-halogenated succinimide take place following halogenation reaction, thereby obtain the compound shown in formula A:

[0193]

[0194] More preferably, the compound shown in formu...

Embodiment 1

[0249] Example 1: N-(5-(7-amino-1-cyclopentyl-5-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2 -Methoxypyridin-3-yl)-2,4-difluorobenzenesulfonamide (Compound 1)

[0250]

[0251] Preparation:

[0252] Step 1: Synthesis of 3-bromo-6-(2,5-methyl-1H-pyrrol-1-yl)-2-methylpyridine

[0253]

[0254] A mixture of 2-amino-5-bromo-6-methylpyridine (38.2g, 204mmol), 2,5-hexanedione (36mL, 306mmol), p-toluenesulfonic acid monohydrate (1.94g, 10.2mmol) and A three-necked flask of 380mL toluene was connected with a water separator and a condenser, and the reaction mixture was refluxed for 6h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (500 mL), washed with water (200 mL×2) and saturated brine (200 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (silica gel, petroleum ether / ethyl acetate=100:1, v / v) to obtain the product as a brown oil (41.4 g, yield 76%).

[025...

Embodiment 2

[0297] Example 2: N-(5-(7-amino-1-cyclopentyl-5-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2 -Methoxypyridin-3-yl)-4-cyanobenzenesulfonamide (compound 2)

[0298]

[0299] Step 1: Synthesis of N-(5-bromo-2-methoxypyridin-3-yl)-4-cyanobenzenesulfonamide

[0300]

[0301] A solution of 4-cyanobenzenesulfonyl chloride (482 mg, 2.4 mmol) in dichloromethane (5 mL) was added dropwise to 3-amino-5-bromo-2-methoxypyridine (0.406 g, 2 mmol) and pyridine (237 mg, 3 mmol) in dichloromethane (5 mL), the reaction mixture was stirred at room temperature for 4 h. Water (25 mL) was added to the reaction mixture, and the resulting mixture was extracted with dichloromethane (30 mL×3). The combined organic layers were washed with water (30 mL×2) and saturated brine (30 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was separated by column chromatography (silica gel, petroleum ether / ethyl acetate=7:1, v / v) to obtain the product as a yellow solid (...

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 compound as represented by formula I, pharmaceutically acceptable salt, preparation method, use and pharmaceutical composition thereof. The compound represented by formula I is as follows:_(Formula I).The compound as represented by formula I has more excellent anti-cancer or anti-tumor effect, can inhibit various kinases inside cell and on cell surface simultaneously, and therefore has more efficient anti-cancer or anti-tumor effect, the kinases comprising PI3-K kinase and mTOR kinase. The pharmaceutical composition provided in the present invention can be used for treating cerebral cancer, glioblastoma, cervicocerebral cancer, lung cancer, melanoma, liver cancer, renal cancer, acute leukemia, chronic leukemia、non-small cell lung cancer、prostate cancer, thyroid cancer, skin cancer, colon cancer, rectal cancer, pancreatic cancer, ovarian cancer, breast cancer, myelodysplasia syndromes, esophageal cancer, sarcoma, osteosarcoma and rhabdomyoma.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a substituted naphthyridin-2-one compound, a preparation method, an application and a pharmaceutical composition. Background technique [0002] The research and development of anticancer drugs is a very challenging and significant field in today's life sciences. In recent years, with the rapid development of molecular biology and the further understanding of the occurrence, development and mechanism of cancer, the signal transduction in malignant tumor cells, the regulation of cell cycle, the induction of apoptosis, angiogenesis and the relationship between cells and cells Various basic processes such as the interaction of the extracellular matrix are being gradually elucidated. Therefore, it has become one of the important fields of current drug research and development to find and discover new anti-tumor drugs with high efficiency, low toxicity and strong specific...

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
IPC IPC(8): C07D471/04A61P35/00A61P35/02
CPCC07D471/04A61P35/00A61P35/02
Inventor 易崇勤许恒陶晶林松文韩方斌钟学超
Owner NEW FOUNDER HLDG DEV LLC
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