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

Tricyclic substituted piperidine diketones

A technology of compound and cycloalkyl, applied in the field of derivative compounds represented by the formula or their pharmaceutically acceptable salts, to achieve the effect of excellent pharmacokinetic properties

Active Publication Date: 2022-03-29
MEDSHINE DISCOVERY INC
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Methamides have many side effects, especially peripheral neuropathy

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
  • Tricyclic substituted piperidine diketones
  • Tricyclic substituted piperidine diketones
  • Tricyclic substituted piperidine diketones

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0117] Example 1: WX001

[0118]

[0119] Step 1: Synthesis of intermediate WX001–2

[0120] WX001-1 (11 g, 79.64 mmol) was dissolved in dichloromethane (100 mL) at room temperature, followed by the addition of diisopropylethylamine (36.03 g, 278.74 mmol, 48.55 mL). The reaction mixture was cooled to 0°C, then chloromethyl ether (10.7 g, 132.90 mmol, 10.09 mL) was added, the reaction mixture was warmed to room temperature and stirred for 2 hours. After the reaction was completed, water (100 mL) was added for dilution, and the organic phase was collected after liquid separation, and the aqueous phase was extracted with dichloromethane (50 mL×2). Combine the organic phases, dry the organic phase with anhydrous sodium sulfate, filter and concentrate under reduced pressure to obtain a residue, and the resulting residue is separated by column chromatography (eluent: petroleum ether / ethyl acetate=100 / 0–9 / 1, volume ratio), to obtain intermediate WX001–2. 1 H NMR (400MHz, CDCl ...

Embodiment 2

[0131] Example 2: WX002

[0132]

[0133] Step 1: Synthesis of intermediate WX002–2

[0134] At room temperature, WX002-1 (5g, 34.68mmol) was dissolved in dichloromethane (70mL), and then N-iodosuccinimide (7.80g, 34.68mmol) and p-toluenesulfonic acid (1.98g , 10.40mmol), the reaction mixture was stirred at room temperature for 30 minutes. After the reaction was completed, water (50 mL) was added for dilution, and the organic phase was collected after liquid separation, and the aqueous phase was extracted with dichloromethane (50 mL×2). The organic phases were combined, dried with anhydrous sodium sulfate, filtered, and the solvent was removed from the filtrate under reduced pressure to obtain the target intermediate WX002–2. 1 HNMR (400MHz, CDCl 3 )δ: 7.96 (d, J = 8.4Hz, 1H), 7.76 (dd, J = 3.2, 8.4Hz, 2H), 7.58 (t, J = 7.7Hz, 1H), 7.46–7.37 (m, 1H), 7.32–7.24(m,1H),4.95(s,1H).

[0135] Step 2: Synthesis of intermediate WX002–3 Intermediate WX002–2 (9 g, 33.33 mmol) wa...

Embodiment 3

[0140] Embodiment 3: the hydrochloride of WX003

[0141]

[0142] Step 1: Synthesis of intermediate WX003–2

[0143] At room temperature and under nitrogen protection, WX003-1 (9.5g, 65.45mmol) and tert-butyl 2-bromoacetate (14.04g, 71.99mmol, 10.64mL) were dissolved in N,N-dimethylformamide (100mL) , then slowly added potassium carbonate (9.05g, 65.45mmol) in batches, the reaction mixture was heated to 60°C and stirred for 12 hours, then the reaction system was cooled to 30°C, and sodium hydrogen (2.62g, 65.45mmol, purity : 60%), was heated to 60 ℃ again and continued stirring reaction for 2 hours. After the reaction was completed, it was cooled to room temperature, quenched by adding water (100 mL), and extracted with ethyl acetate (200 mL×2). The organic phases were combined, washed with half-saturated brine (150 mL×3), dried over anhydrous sodium sulfate, filtered, and the solvent was removed from the filtrate under reduced pressure. The obtained residue was separate...

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
molecular weightaaaaaaaaaa
Login to View More

Abstract

Disclosed are a series of tricyclic substituted piperidine diketone compounds and their application in the preparation of drugs for the treatment of CRBN protein-related diseases, specifically disclosing derivative compounds represented by formula (I) or pharmaceutically acceptable salts thereof .

Description

[0001] References to related applications [0002] This application claims the following priority: [0003] CN201811044122.5, application date 2018-09-07; [0004] CN201811353938.6, application date 2018-11-14; [0005] CN201910223413.9, application date 2019-03-22. technical field [0006] The present invention relates to a series of compounds with tricyclic substituted piperidine diketones and their application in the preparation of medicines for treating diseases related to CRBN protein, in particular to derivative compounds represented by formula (I) or pharmaceutically acceptable salts thereof . Background technique [0007] Thalidomide, whose trade name is thalidomide, was first synthesized by the German Granite Company. From the second half of the 1950s to the early 1960s, it was sold as a sedative in more than 40 countries, and it was also widely used as an antiemetic for pregnant women, which eventually led to the tragedy of tens of thousands of babies with seal...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/04C07D401/00C07D493/00A61K31/445
CPCC07D493/04C07D405/04C07D491/048C07D405/14A61P35/00A61K31/4525A61K31/4741A61K31/454A61K31/5377A61K31/541A61K31/496A61K31/4545A61K31/45C07D401/14
Inventor 罗云富雷茂义王勇黎健陈曙辉
Owner MEDSHINE DISCOVERY 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