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

Multi-kinase inhibitor compound, and crystal form and use thereof

Active Publication Date: 2019-02-07
TRANSTHERA SCIENCES (NANJING) INC
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes new compounds that can inhibit the process of cell division (mitosis) and the formation of new blood vessels (angiogenesis). These compounds are more effective because they target multiple enzymes, leading to better pharmacological activity. Additionally, these compounds have improved properties for absorption, distribution, and toxicity. This makes them more likely to be effective drugs.

Problems solved by technology

When an error occurs in the mitosis process, chromosomal number in the cell will be abnormal, which may lead to cell death or promote the development of normal cells to tumor cells.
Aurora A has now been demonstrated to be an oncogene, whose overexpression blocks the correct assembly of mitotic checkpoint complexes, resulting in genetic instability and tumor formation.
In addition, Aurora kinases are ineffective against non-proliferating cells since they are expressed and activated in mitosis.
However, no multi-kinases inhibitors that are effective against the above kinases simultaneously are available.

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
  • Multi-kinase inhibitor compound, and crystal form and use thereof
  • Multi-kinase inhibitor compound, and crystal form and use thereof
  • Multi-kinase inhibitor compound, and crystal form and use thereof

Examples

Experimental program
Comparison scheme
Effect test

embodiments

[0153]The present invention will be further described in detail below with reference to the accompanying drawings, so as to illustrate the purposes, technical solutions and advantages of the present invention more clearly. It is apparent that the described embodiments are only a part of the embodiments of the invention, rather than all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts are within the scope of the present invention.

preparation example 1

mediate 1-(4-methoxybenzyl)-5-methyl-4-nitro-1H-pyrazol-3-amine

[0154]

Step 1: Synthesis of N-(5-methyl-1H-pyrazol-3-yl)acetamide

[0155]

[0156]5-methyl-1H-pyrazol-3-amine (300 g, 3.09 mol, 1.0 eq) was weighted into a 5 L round bottom flask, dissolved by adding water (2800 mL) with mechanical stirring at room temperature. Sodium bicarbonate (780 g, 9.28 mol, 3 eq) was added in portions, following by stirring for another 30 min after the addition. Then, acetic anhydride (592 ml, 6.2 mol, 2 eq) was added dropwise and slowly to the reaction system over about 1 h at controlled drop rate. At this point, a large amount of foamy white solid was produced. The temperature was raised to 100° C. and the reaction system was stirred for 2 h. The solid was gradually dissolved, and the system became clarification. Then heating was stopped, and the system was cooled to room temperature. After stirring overnight, a large amount of white crystalline solid precipitated. Another batch of 5-methyl-1H-pyrazol...

preparation example 2

mediate (6-bromo-4-iodo-pyridin-3-yl)(2-chlorophenyl)methanone

[0166]

Step 1: Synthesis of (6-bromopyridin-3-yl)(2-chlorophenyl)methanol

[0167]

[0168]Anhydrous tetrahydrofuran (500 mL) and 2,5-dibromopyridine (100.0 g, 0.42 mol, 1.0 eq) were added into a 2 L four-necked flask, and the mixture was cooled to 2° C. with stirring in the presence of an ice water bath. Isopropyl magnesium chloride (210.5 mL, 2.0 M, 0.42 mol, 1.0 eq) was then added dropwise over about 0.5 h at a controlled temperature of no more than 10° C. The reaction system was stirred at room temperature (20° C.) for 1 h, then cooled to 10° C. with an ice water bath. A solution of 2-chlorobenzaldehyde (62.3 g, 0.443 mol, 1.05 eq) in tetrahydrofuran (200 mL) was added dropwise over about 0.5 h. After stirring at 10° C. for 2 h, the reaction endpoint was monitored by TLC. Saturated aqueous solution of ammonium chloride (300 mL) was added into the reaction system. After stirring for 10 min, the organic phase was separated fro...

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

PropertyMeasurementUnit
Angleaaaaaaaaaa
Angleaaaaaaaaaa
Angleaaaaaaaaaa
Login to View More

Abstract

The present invention relates to a compound as represented by formula (I) or a pharmaceutically acceptable salt and stereoisomer thereof, wherein R1, R2, X, Y, P, W, and Ar are as defined in the description. The compound of formula (I) of the present invention can be used in the preparation of a drug for treating cancers mediated by abnormality of multi-kinases. Also provided is a crystal form I of a compound 4-(5-(2-chlorophenyl)-3-methyl-2,10-dihydropyrazolo[4,3-b]pyrido[4,3-e][1,4]diazepin-8-yl)morpholine, wherein in an X-ray powder diffraction pattern of crystal form I, there are characteristic peaks at 7.4±0.20, 17.9±0.2°, 18.9±0.2°, 19.4±0.2°, 21.5±0.2°, and 23.7±0.2°.

Description

[0001]This application claims the priority of the Chinese patent application of No. 201611174146.3, titled “A SYNTHESIS METHOD OF MULTI-KINASES INHIBITOR AND USE THEREOF”, filed with State Intellectual Property Office of the P.R.C on Dec. 13, 2016; the Chinese patent application of No. 201710426594.6, titled “MULTI-KINASES INHIBITOR AND USE THEREOF”, filed with State Intellectual Property Office of the P.R.C on Jun. 8, 2017; and the Chinese patent application of No. 201710593933.X, titled “CRYSTAL FORM OF MULTI-KINASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF”, filed with State Intellectual Property Office of the P.R.C on Jul. 20, 2017, the contents of which are incorporated into the present application by reference in its entirety.TECHNICAL FIELD[0002]The invention belongs to the field of medicine technology, particularly relates to a multi-kinases inhibitor compound, a crystal form and use thereof.BACKGROUND[0003]Normal cell division is essential for the health of the body...

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): C07D471/14
CPCC07D471/14C07D487/04C07D519/00C07B2200/13C07D491/08A61K45/06A61K31/551A61K31/5517A61P35/00A61P35/02C07D491/048C07D491/107
Inventor WU, FRANK
Owner TRANSTHERA SCIENCES (NANJING) INC
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