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

Pyrazolo[3, 4-d]pyrimidin-3-one derivative, and pharmaceutical composition and application thereof

A technology of derivatives and compounds, applied to pyrazolo[3,4-d]pyrimidin-3-one derivatives, their pharmaceutical compositions and application fields, can solve problems such as drug listing

Pending Publication Date: 2021-09-14
SHANGHAI DE NOVO PHARMA
View PDF4 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are currently no drugs targeting Wee1 and PLK1 on the market

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
  • Pyrazolo[3, 4-d]pyrimidin-3-one derivative, and pharmaceutical composition and application thereof
  • Pyrazolo[3, 4-d]pyrimidin-3-one derivative, and pharmaceutical composition and application thereof
  • Pyrazolo[3, 4-d]pyrimidin-3-one derivative, and pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0314] Example 1: 6-(-2H- allyl -6-((4-(4- methylpiperazine -1- yl) phenyl) amino) -3- oxo -2,3- dihydro -1H- pyrazolo [3,4-d] pyridine -1- yl) -4- ethyl

[0315]

[0316] Step 1: Intermediate 1.1(298mg, 0.79mmol), 2- allyl -6- (methylthio) -1H- pyrazolo [3,4-d] pyrimidine -3(2H)- one (137mg, 0.72mmol), N,N'- dimethylethylenediamine (N-dimethylethylenediamine) The reaction solution was cooled to room temperature and filtered. The filter cake was washed with ethyl acetate. The filtrates were combined and concentrated under reduced pressure. The residue was purified by prep-TLC (petroleum ether / ethyl acetate = 1 / 1) to obtain compound 1(270mg) as yellow oil. m / z:[M+H] + 399.2。

[0317] Step 2: m-chloroperoxybenzoic acid (71mg, 0.35mmol) was added to the toluene (5mL) solution of Compound 1(70mg, 0.18mmol). After the reaction solution was stirred at room temperature for 1 hour, 4-(4- methylpiperazine) aniline (67mg, 0.35mmol) and N,N- diisopropylethylamine (45mg) The reaction system...

Embodiment 2～73

[0318] Examples 2 ~ 73: Synthesis of Compounds 1-2 ~ 1-73

[0319] With the synthetic method of compound 1-1, Using intermediates 1.2 ~ 1.12, 2.1 ~ 2.7, 2.15, 2-9 ~ 2.11, 2.13, 3.1 ~ 3.6, 4.14 ~ 4.16, 4.4, 4.5, 4.17, 4.21, 4.22, 4.12, 4.1 4.2, 4.35, 4.8, 4.27 ~ 4.31, 4.3, 4.32, 4.20, 4.9, 4.37, 4.10, 4.38, 4.39, 4.11, 4.40, 4.41 or 1.13 to obtain compounds 1-2 ~ 1-73.

[0320]

[0321] Table 5:

[0322]

[0323]

[0324]

[0325]

[0326]

[0327]

[0328]

[0329]

[0330]

[0331]

[0332]

Embodiment 75～85

[0333] Examples 75 ~ 85: Synthesis of Compounds 2-1 ~ 2-11

[0334] Using the synthetic method of compound 1-1, using intermediates 1.1, 1.3, 1.13, 1.2, 1.4, 1.10, 2.1, 2.2, 2.15, 3.1 and 4.34 as starting materials, the 4-(4- methylpiperazine) aniline in step 2 was replaced with 3- methoxy-4-.

[0335]

[0336] Table 6:

[0337]

[0338]

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 pyrazolo[3, 4-d]pyrimidin-3-one derivative as shown in a formula (I) and / or pharmaceutically acceptable salt thereof, a composition containing the compound as shown in the formula (I) and / or pharmaceutically acceptable salt thereof, a preparation method of the derivative, and an application of the derivative as Wee1 and / or PLK1 inhibitors and as sensitizers for chemotherapy or radiotherapy of cancer. The pyrazolo[3, 4-d]pyrimidin-3-one derivative disclosed by the invention can effectively inhibit Wee1 and / or PLK1 and related signal channels, and has a good effect of treating and / or relieving cancers.

Description

Technical field [0001] The invention relates to a pyrazolo [3,4-d] pyrimidine -3- one derivative and its pharmaceutically acceptable salt which can inhibit Wee1 and / or PLK1 and its signal pathway, a pharmaceutical composition containing the derivative and its pharmaceutically acceptable salt, and the application of the derivative and its pharmaceutically acceptable salt in treating diseases mediated by Wee1 and / or PLK1 and preparing medicines for treating diseases mediated by Wee1 and / or PLK1. technical background [0002] Wee1(Wee1 G2 detection point kinase; Gene number: 7465) and PLK1(polo-like kinase 1; Gene number: 5347) is a member of serine / threonine protein kinase family. [0003] Wee1 can directly phosphorylate cyclin-dependent kinase 1(CDK1), and the phosphorylation site is tyrosine 15 residue of CDK1, which is an inhibitory phosphorylation site and negatively regulates CDK1 activity. The activation of G2 detection point is mainly through inhibiting mitosis and promoting...

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): C07D519/00C07D487/04C07D471/22C07D487/22C07D513/22A61P35/00A61P35/02A61P35/04A61K31/5383A61K31/519A61K31/5377A61K31/5386
CPCC07D519/00C07D487/04C07D471/22C07D487/22C07D513/22A61P35/00A61P35/02A61P35/04
Inventor 刘晓辉杨和平杜坚钢付光亮
Owner SHANGHAI DE NOVO PHARMA
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