Spiro aryl sulfone as protein kinase inhibitor

A technology of cycloalkyl and alkyl, which is applied in the direction of medical preparations containing active ingredients, organic active ingredients, organic chemistry, etc., and can solve problems such as unsatisfactory curative effect and drug loss of effectiveness

Active Publication Date: 2016-10-12
QILU PHARMA
View PDF12 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] However, although more than half of NSCLC patients have a good effect on Crizotinib, drug resistance always occurs with the prolongation of treatment time, so that the drug loses its e

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
  • Spiro aryl sulfone as protein kinase inhibitor
  • Spiro aryl sulfone as protein kinase inhibitor
  • Spiro aryl sulfone as protein kinase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Compound 1: 5-ChloroN4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(9-methyl-3,9-diazaspiro[5.5] Undec-3-yl)phenyl)pyrimidine-2,4diamine

[0104]

Embodiment 1A

[0106] 9-Benzyl-2,4-dioxo-3,9-diazaspiro[5.5]undecane-1,5-dicarbonitrile

[0107]

[0108] Ammonium acetate (2.04 g, 26.42 mmol, 0.10 eq) was added to a solution of cyanoacetate (90 g, 796 mmol, 3.00 eq) in methanol (100 mL) at 5-8°C; then 1-benzyl Basepiperidin 4-ketone (50 grams, 0.264 moles) was added to the above reaction mixture; then, below 10°C, ammonia water (46.3 grams, 370 mmoles, 1.40 equivalents) was added to the reaction mixture, and the mixture was Stir at -5°C for 1 hour. The reaction mixture was then warmed to 20°C (room temperature) and stirred for 20 hours. LCMS showed formation of product. Water (100 mL) was added to the mixture and heated to 55°C. The pH was adjusted to 4 by adding concentrated hydrochloric acid (12M) and the temperature was kept not exceeding 70°C. Then the reaction solution was cooled to 10° C., stirred for 30 minutes and then filtered. The filter cake was washed with water and left to air dry to afford the title compound (66 g, 7...

Embodiment 1B

[0110] 1′-Benzyl-3,7-diazaspiro[bicyclo[3.3.1]nonane-9,4′-piperidine]-2,4,6,8-tetraone

[0111]

[0112] A mixture of Example 1A (1.00 g, 3.10 mmol, 1.00 eq) in sulfuric acid (88%, 4 mL) was stirred at 60° C. for 4 hours. Water (1.4 mL) was then added to the reaction solution, heated to 100°C and stirred for 1 hour. Further water (5 mL) was added to the reaction mixture, cooled to 10° C., stirred at 10° C. for 30 minutes, and then filtered. The filter cake was washed with cold water (5 mL) and dried to give the title compound (1.11 g, crude) as a white solid. 1 H NMR (400MHz, CDCl 3 ): 11.87 (s, 2H), 9.56 (br.s., 1H), 7.47 (s, 5H), 4.34 (d, J=4.4Hz, 2H), 3.75 (br.s., 1H), 3.22 ( br.s., 4H), 1.88 (br.s., 4H).

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 discloses a spiro aryl sulfone compound, and especially relates to the compound represented by the formula (I) as an ALK inhibitor.

Description

technical field [0001] The present invention relates to spirocyclic aryl sulfone compounds, especially compounds of formula (I) as ALK inhibitors. Background technique [0002] Protein kinases can regulate all aspects of the cell cycle; abnormal expression of protein kinases can cause diseases, and diseases can also cause abnormal expression of protein kinases. These diseases include cancer, inflammation and diabetes, etc., so protein kinases have gradually become more popular drugs target. [0003] Since the launch of Gleevec in 2001, many protein kinases have become attractive targets for cancer therapy. Among them, anaplastic lymphoma kinase (ALK) has attracted a lot of attention due to its potential oncogene and important role in the pathogenesis of many human cancers, such as ALCLS, non-small cell lung cancer, breast cancer, colon Rectal cancer, neuroblastoma, ovarian cancer, etc. [0004] Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) and a mem...

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): C07D471/10C07D401/12A61K31/506A61K45/06A61P35/00
CPCC07D401/12C07D471/10Y02P20/55
Inventor 丁照中陈曙辉赵保平刘希乐鄢笑非张路
Owner QILU PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap