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

JNK inhibitor, pharmaceutical composition and application

A technology of solvates and polymorphs, applied in the field of compounds that can inhibit JNK activity, can solve the problems of complicated liver fibrosis reversal process and no drugs on the market

Pending Publication Date: 2021-11-26
WUHAN LL SCI & TECH DEV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the reversal process of liver fibrosis is very complicated, and many signaling pathways such as the known MAPK / EKR signaling pathway, MAPK signaling pathways such as SAPK / JNK and MEK5, and non-MAPK signaling pathways such as PI3K / Akt and Notch all play an important role in it. effect
[0006] Currently, there are no drugs on the market that treat diseases such as fibrotic diseases through the JNK inhibitory pathway

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
  • JNK inhibitor, pharmaceutical composition and application
  • JNK inhibitor, pharmaceutical composition and application
  • JNK inhibitor, pharmaceutical composition and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0119] Example 1: 2,11-diaza-1(2,4)-pyrimidinecycloundecane-1 5 - Preparation of formamide (L001)

[0120]

[0121] 1.1 Preparation of compound (8-aminooctyl) tert-butyl carbamate (L001-2)

[0122] 1,8-Octanediamine (2 g, 13.86 mmol) and DIEA (537 mg, 4.16 mmol) were dissolved in DCM (50 mL), and to the solution was slowly added dropwise (Boc) 2 A solution of O (106 mg, 4.85 mmol) in DCM (20 mL) was added dropwise, and the reaction was stirred at room temperature for 12 hours. After the reaction was completed, the reaction solution was adjusted to pH=3~4, extracted with water (50mL*3), the aqueous phase was combined, then the aqueous phase was adjusted to pH=9~10, then extracted with DCM (50mL*3), the organic phase was collected, and no After drying with sodium sulfate, spin-dry to obtain 600 mg of white solid product, which is the title compound L001-2, yield: 12%, LC-MS [M+H] + :245.0.

[0123] 1.2 Preparation of compound (8-((5-carbamoyl-2-chloropyrimidin-4-yl)amino)...

Embodiment 2

[0130] Example 2: Compound 2,10-diaza-1(2,4)-pyrimidinylcyclodecane-1 5 - Preparation of formamide (L002)

[0131]

[0132] 2.1 Preparation of compound (7-aminoheptyl) tert-butyl carbamate (L002-2)

[0133] L002-1 (2.0g, 15.36mmol) and (Boc) 2 O (0.67g, 3.07mmol) was dissolved in DCM (100mL), and the reaction solution was reacted at room temperature for 4h. TLC (DCM:MeOH=10:1) showed that the reaction was complete. The reaction solution was added dropwise to DCM (100mL) and water (50mL), the aqueous phase was extracted with DCM (100mL*3), the organic phases were combined, washed with saturated brine (100mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated Column (DCM:MeOH=20:1, adding 1% ammonia water) gave 0.6 g of colorless liquid, which was the title compound L002-2.

[0134] 2.2 Preparation of compound (7-((5-carbamoyl-2-chloropyrimidin-4-yl)amino)heptyl)carbamate tert-butyl ester (L002-3)

[0135] L002-2 (0.60g, 2.60mmol), 2,4-dich...

Embodiment 3

[0141] Example 3: Compound 6-oxa2,10-diaza-1(2,4)-pyrimidinylcyclodecane-1 5 - Preparation of formamide (L003)

[0142]

[0143] 3.1 Preparation of compound (3-(3-aminopropoxy)propyl) tert-butyl carbamate (L003-2)

[0144] 2,2'-Oxybis(ethylamine) (750 mg, 5.7 mmol) and DIEA (220 mg, 1.7 mmol) were dissolved in DCM (50 mL), and to the solution was slowly added dropwise (Boc) 2 A solution of O (433 mg, 2 mmol) in DCM (20 mL) was added dropwise, and the reaction was stirred at room temperature for 12 hours. After completion of the reaction, dilute hydrochloric acid to adjust pH=3~4, extract with water (50mL*3), combine the aqueous phase, then adjust the pH of the aqueous phase=9~10, then extract with DCM (50mL*3), collect the organic phase, After drying over sodium sulfate, spin-dry to obtain 250 mg of a white solid product, which is the title compound L003-2, yield: 19%.

[0145] 3.2 Preparation of compound (3-(3-((5-carbamoyl-2-chloropyrimidin-4-yl)amino)propoxy)propyl)ca...

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 provides a compound represented by a formula (I) as well as a racemate, stereoisomer, tautomer, isotope label, solvate, polymorph, nitrogen oxide or pharmaceutically acceptable salts thereof. The compound can be used as a JNK inhibitor. The invention also provides a preparation method of the compound shown in the formula (I), a pharmaceutical composition containing the compound shown in the formula (I), and application of the compound shown in the formula (I) to preparation of a medicine for treating diseases which can be treated by inhibiting JNK activity.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a compound capable of inhibiting JNK activity, its pharmaceutical composition and application. Background technique [0002] Mitogen-activated protein kinases (mitogen-activated protein kinases, MAPK) is one of the important pathways in eukaryotic signal transmission network. The MAPK chain consists of three classes of protein kinases MAP3K-MAP2K-MAPK, which transmit upstream signals to downstream response molecules through sequential phosphorylation. In mammals, there are three major MAPK signal transduction pathways: extracellular signal-regulated kinase (ERK1 / 2), c-Jun N-terminal kinase (JNK) and p38 signal pathway, among which ERK1 / 2 signal transduction pathway regulates Cell growth and differentiation, JNK and p38 MAPK signal transduction pathways play an important role in stress responses such as inflammation and apoptosis. JNK is an important member of the MAPK family, which can ...

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): C07D487/08C07D498/08A61K31/529A61P1/16A61P35/00A61P31/14A61P3/10A61P3/00A61P11/00A61P13/12A61P37/06A61P19/02A61P11/06A61P27/02A61P1/00A61P37/08A61P1/04A61P25/28A61P3/04A61P9/10A61P17/06A61P17/02A61P17/00A61P29/00A61P25/08A61P25/16
CPCC07D487/08C07D498/08A61P1/16A61P35/00A61P31/14A61P3/10A61P3/00A61P11/00A61P13/12A61P37/06A61P19/02A61P11/06A61P27/02A61P1/00A61P37/08A61P1/04A61P25/28A61P3/04A61P9/10A61P17/06A61P17/02A61P17/00A61P29/00A61P25/08A61P25/16
Inventor 李金平娄军郭晓丹柳力彭微陈晓亚钱丽娜王朝东
Owner WUHAN LL SCI & TECH DEV
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