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

Nitrogen-containing heterocyclic compound as well as preparation method and application thereof

A technology of nitrogen heterocyclic compounds and compounds, applied in the field of medicine

Active Publication Date: 2021-02-02
上海弘翊生物科技有限公司 +1
View PDF2 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] BRD4 inhibitors have good application prospects as drugs in the pharmaceutical industry. There are no drugs on the market at present. In order to achieve better therapeutic effects and meet market demand, We hope to develop a new generation of selective BRD4 inhibitors with high efficiency and low toxicity

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
  • Nitrogen-containing heterocyclic compound as well as preparation method and application thereof
  • Nitrogen-containing heterocyclic compound as well as preparation method and application thereof
  • Nitrogen-containing heterocyclic compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0123] Preparation Example 1: Intermediate 1 (INT-01): 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2- base)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

[0124]

[0125] The first step: 4-bromo-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (I-02)

[0126] Compound I-01 (3.0g) and NaOH (1.5g) were dissolved in ethanol / distilled water (20mL / 20mL), stirred overnight at room temperature, LCMS monitoring was completed, the reaction solution was concentrated, extracted with EA, the organic phase was dried and concentrated, The crude product I-02 (1.3 g) was obtained directly. LCMS (ES, m / z): 227.1 [M+H] + .

[0127] The second step: 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,6-dihydro- 7H-pyrrolo[2,3-c]pyridin-7-one compound I-02 (1.3g), compound pinacol diboronate (2.7g), Pd 2 (dba) 3 (120mg), X-phos (250mg) and KOAc (1.3g) were dissolved in dioxane (25mL), stirred overnight at 80°C, LCMS monitoring was complete, the reaction solution was extra...

preparation Embodiment 2

[0129] Intermediate Two (INT-02): 2,5-Dimethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2,5-Dihydro-4H-pyrazolo[4,3-c]pyridin-4-one

[0130]

[0131] The first step: 1H-pyrazolo[4,3-c]pyridin-4-ol (I2-02)

[0132] Compound I2-01 (5.0g) and H 2 O (2.0 mL) was added to ACOH (200 mL), stirred at 100°C overnight, LCMS detected that the reaction was complete, the solvent was spin-dried, the residue was dissolved in methanol, filtered, and the filtrate was concentrated to directly obtain compound I2-02 (4.2 g). LCMS (ES, m / z): 136.0 [M+H] + .

[0133] The second step: 7-bromo-1H-pyrazolo[4,3-c]pyridin-4-ol (I2-03)

[0134] Compound I2-02 (4.2g) was added to ACOH (80mL), stirred at room temperature, and then Br 2 (1.8ml) was added to the reaction, stirred at room temperature overnight, LCMS detected that the reaction was complete, the solvent was directly concentrated and spin-dried to obtain compound I2-03 (2.5g). LCMS (ES, m / z): 214.0 [M+H] + .

[0135] The third...

preparation Embodiment 3

[0140] INT-03: 1,5-Dimethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,5- Dihydro-4H-pyrazolo[4,3-c]pyridin-4-one

[0141]

[0142] The first step: 7-bromo-1,5-dimethyl-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (I3-01)

[0143] Compound I2-03 (2.5g), CH 3 I (5.0g) and CS 2 CO 3(9.5g) was dissolved in DMF (80mL), stirred overnight at 50°C, and the reaction was detected by LCMS, then the reaction solution was added to EA, washed with distilled water (50mL*3), and the organic phase was washed with anhydrous Na 2 SO 4 After drying, filtration and concentration, the residue was separated and purified by silica gel chromatography (PE:EA=1:3) to obtain compound I3-01 (500 mg). LCMS (ES, m / z): 242.0 [M+H] + .

[0144] The second step: 1,5-dimethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,5- Dihydro-4H-pyrazolo[4,3-c]pyridin-4-one (INT-03)

[0145] Compound I3-01 (450mg), pinacol diboronate (700mg), Pd(PPh 3 ) 4 (220mg) and TEA (600mg) were dissolved in ...

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 invention relates to a nitrogen-containing heterocyclic compound (as shown in a formula I) serving as a BRD4 inhibitor, a pharmaceutical composition containing the nitrogen-containing heterocycliccompound, a preparation method of the nitrogen-containing heterocyclic compound and application of the nitrogen-containing heterocyclic compound to preparation of drugs for treating diseases relatedto BRD4, such as cancer, inflammation, cardiovascular diseases, metabolic diseases and immune diseases.

Description

technical field [0001] The invention belongs to the field of medicine, in particular, it relates to a nitrogen-containing heterocyclic compound, a preparation method thereof and a pharmaceutical composition containing the compound, and they are used as BRD4 inhibitors in the preparation and treatment of cancer, inflammation, cardiovascular disease, metabolic Use in medicine for diseases and immune diseases. [0002] Background of the invention [0003] Tumor is one of the major diseases that seriously endanger human health and life. With the aging of the population, the incidence of malignant tumors is increasing year by year, but the overall cure rate of tumors is still low and the recurrence rate is high. Therefore, there are still huge unmet clinical needs in tumor prevention and treatment. The abnormality of epigenetic regulation is one of the important factors leading to tumorigenesis. Epigenetics refers to changes in gene expression levels based on non-gene sequence c...

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): C07D471/04C07D519/00A61P35/00A61P35/04A61P9/00A61P37/06A61P3/00A61P27/02A61P35/02A61P29/00A61P19/02A61P17/00A61P11/00A61P13/10A61P9/12A61P9/10A61P17/06A61P1/04A61P1/16A61P1/18A61P1/02A61P27/16A61P3/10A61P3/06A61P19/06A61K31/437A61K31/4985A61K31/506A61K31/444
CPCC07D471/04C07D519/00A61P35/00A61P35/04A61P9/00A61P37/06A61P3/00A61P27/02A61P35/02A61P29/00A61P19/02A61P17/00A61P11/00A61P13/10A61P9/12A61P9/10A61P17/06A61P1/04A61P1/16A61P1/18A61P1/02A61P27/16A61P3/10A61P3/06A61P19/06
Inventor 吴荣光李佳易德武周宇波庞淞元李聪苏明波朱霞霞
Owner 上海弘翊生物科技有限公司
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