Substituted piperazine compound and use method and use thereof

A compound and nitrogen oxide technology, applied in the field of compounds for the treatment of central nervous system dysfunction, replacing piperazine compounds, can solve the problems of reduced serotonin release and serotonin concentration, and achieve good bioavailability, The effect of stable properties and good clinical application prospects

Active Publication Date: 2016-12-21
SUNSHINE LAKE PHARM CO LTD
View PDF2 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But after using SSRIs, it also activates 5-HT in the presynaptic membrane 1A Autoreceptors, resulting in decreased release of serotonin, lowering intersynaptic serotonin concentration

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
  • Substituted piperazine compound and use method and use thereof
  • Substituted piperazine compound and use method and use thereof
  • Substituted piperazine compound and use method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0340] Example 1 3-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)benzyl Amide

[0341]

[0342] Step 1) Synthesis of 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile

[0343] At 0°C, 4-chlorobutyryl chloride (9.60g, 68.00mmol) was added dropwise to a solution of dichloromethane (90mL) containing aluminum chloride (9.00g, 68.00mmol), and the mixture was stirred for 30 minutes, then continued to A solution of 5-cyanindole (8.10 g, 57.00 mmol) in dichloromethane (800 mL) was added dropwise thereto. The reaction solution was returned to room temperature, and after stirring for 2 hours, the reaction solution was slowly poured into a mixture of ice (50 g) and concentrated hydrochloric acid (50 mL), and then stirred at room temperature for 20 hours. The resulting mixture was filtered with suction, and the filter cake was washed with water (10 mL) and ethyl acetate (10 mL) successively. After the filter cake was dried, the title compound was obtained as a...

Embodiment 2

[0368] Example 2 3-(2-(4-(3-(5-cyano-1H-indol-3-yl)propyl)piperazin-1-yl)pyrimidin-5-yl)benzyl Amide

[0369]

[0370] Step 1) Synthesis of 3-(3-hydroxypropyl)-1H-indole-5-carbonitrile

[0371] 4-cyanophenylhydrazine hydrochloride (3.53g, 20.8mmol) was dissolved in a mixed solvent of dilute sulfuric acid (4%, 50mL) and N,N-dimethylacetamide (10mL), and 3 , 4-Dihydro-2H-pyran (1.9 mL, 20.8 mmol). The reaction solution was heated to 100° C., stirred for 20 hours, cooled to room temperature, and extracted with ethyl acetate (50 mL×3). The combined organic phases were washed with water (50mLx3), then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v)=2 / 1 ) afforded the title compound as a white solid (1.46 g, 35.0%).

[0372] LC-MS(ESI,pos.ion)m / z:201.1[M+H] + ;

[0373] Step 2) Synthesis of 3-(5-cyano-1H-indol-3-yl)pr...

Embodiment 3

[0381] Example 3 2-(2-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)pyrimidin-5-yl)benzyl Amide

[0382]

[0383] Step 1) Synthesis of 4-(5-(2-carbamoylphenyl)pyrimidin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

[0384] The title compound of this step was prepared by referring to the method described in step 5 of Example 1, that is, tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (3.77g, 11.00mmol), (2- Carbamoylphenyl)boronic acid (1.81g, 11.00mmol), Pd(dppf)Cl 2 (732mg, 0.98mmol) and cesium carbonate (10.75g, 33.00mmol) were prepared in a mixed solvent of 1,4-dioxane (45mL) and water (3mL) to obtain a crude product, and the resulting crude product was subjected to silica gel column chromatography Purification (petroleum ether / ethyl acetate (v / v)=5.5 / 1) gave the title compound as a light yellow solid (2.15 g, 50.9%)

[0385] MS(ESI,pos.ion)m / z:384.0[M+H] + ;

[0386] 1 H NMR (400MHz, DMSO-d 6 ):δ(ppm)8.40(s,2H),7.73(s,1H),7.52-7.46(m...

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 present invention relates to a substituted piperazine compound and a use method and use thereof, and further relates to a pharmaceutical composition comprising the substituted piperazine compound and use thereof, wherein the substituted piperazine compound is a compound shown as formula (I) or a stereoisomer, tautomer, nitrogen oxide, solvate, metabolism product, a pharmaceutically acceptable salt or prodrug of the compound shown as the formula (I). The substituted piperazine compound and the pharmaceutical composition comprising the substituted piperazine compound can be used to inhibit 5-hydroxytryptamine reuptake and / or 5-HT1A receptor excitement. The invention also relates to a method for making the substituted piperazine compound and the pharmaceutical composition comprising the substituted piperazine compound, and relates to the use of the substituted piperazine compound and the pharmaceutical composition comprising the substituted piperazine compound in the treatment of central nervous system dysfunction.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to compounds and compositions for treating central nervous system dysfunction, as well as methods and applications thereof. In particular, the present invention is described as a serotonin reuptake inhibitor and / or 5-HT 1A Substituted piperazine compounds that are receptor agonists. Background technique [0002] Serotonin, a neurotransmitter that transmits signals in the brain and nervous system, plays an important role in central nervous system (CNS) dysfunction, especially anxiety, depression, aggression and impulsive mood. Antagonizing or stimulating certain types of 5-HT receptors can effectively regulate central nervous system dysfunction. To date, at least 14 serotonin receptors have been identified. These receptors can be divided into different families, respectively recorded as 5-HT 1 , 5-HT 2 , 5-HT 3 , 5-HT 4 , 5-HT 5 , 5-HT 6 and 5-HT 7 , and the d...

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 Applications(China)
IPC IPC(8): C07D403/12C07D401/12C07D413/12C07D417/12A61K31/506A61K31/496A61P25/22A61P25/24A61P25/18A61P25/20A61P25/14A61P25/28A61P25/16A61P25/30
CPCC07D403/12A61K31/496A61K31/506A61K45/06A61P25/28C07D401/12C07D413/12C07D417/12
Inventor 张英俊金传飞梁海平易超张霁
Owner SUNSHINE LAKE PHARM CO LTD
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