Phenylpiperazine derivatives, using method thereof and uses of the derivatives

An alkyl and drug technology, applied to compounds and compositions for affective disorders, in the field of treatment of central nervous system dysfunction, can solve problems such as deterioration and delayed treatment of SSRIs, and achieve stable properties, good safety, and good metabolic stability. Effect

Active Publication Date: 2016-04-06
SUNSHINE LAKE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, clinical studies of depression have highlighted the lack of response to known SSRIs. Another factor that is often overlooked in antidepressant treatment is that th

Method used

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  • Phenylpiperazine derivatives, using method thereof and uses of the derivatives
  • Phenylpiperazine derivatives, using method thereof and uses of the derivatives
  • Phenylpiperazine derivatives, using method thereof and uses of the derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 14

[0152] Example 14,6-dimethoxy-2-(2-(piperazin-1-yl)phenoxy)pyrimidine

[0153]

[0154] Step 1) Synthesis of tert-butyl 4-(2-((4,6-dimethoxypyrimidin-2-yl)oxy)phenyl)piperazine-1-carboxylate

[0155] 4-(2-hydroxyphenyl)piperazine-1-carboxylic acid tert-butyl ester (0.42g, 1.51mmol), 2-chloro-4,6-dimethoxypyrimidine (0.28g, 1.60mmol) and potassium carbonate (0.42g, 3.02mmol) was sequentially added to DMSO (10mL), and then the reaction solution was heated to 110°C for 20 hours. After the reaction, the reaction solution was cooled to room temperature, washed with water (20 mL), and extracted with ethyl acetate (20 mL×3). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column purification (petroleum ether / ethyl acetate (v / v)=2 / 1) to obtain the title compound as a pale yellow solid (0.44 g, 70.1%).

[0156] MS(ESI,pos.ion)m / z:417.2[M+H] + ;

...

Embodiment 24

[0162] Example 24,6-Dimethyl-2-(2-(piperazin-1-yl)phenoxy)pyrimidine

[0163]

[0164] Step 1) Synthesis of tert-butyl 4-(2-((4,6-dimethylpyrimidin-2-yl)oxy)phenyl)piperazine-1-carboxylate

[0165] The title compound of this step can be prepared by referring to the method described in step 1 of Example 1, that is, tert-butyl 4-(2-hydroxyphenyl)piperazine-1-carboxylate (0.42g, 1.51mmol), 2-chloro-4 , 6-dimethylpyrimidine (0.23g, 1.60mmol) and potassium carbonate (0.42g, 3.02mmol) were reacted in DMSO (10mL) to prepare crude product, which was purified by silica gel column (petroleum ether / ethyl acetate ( v / v) = 2 / 1) to obtain the title compound as a pale yellow solid (0.39 g, 67.2%).

[0166] MS(ESI,pos.ion)m / z:385.2[M+H] + ;

[0167] 1 HNMR (CDCl 3 ,400MHz)δ(ppm):7.21-7.17(m,2H),7.12-7.08(m,2H),6.73(s,1H),3.19-3.17(m,4H),2.90-2.88(m,4H) ,2.36(s,6H),1.44(s,9H).

[0168] Step 2) Synthesis of 4,6-dimethyl-2-(2-(piperazin-1-yl)phenoxy)pyrimidine

[0169] Dissolve ...

Embodiment 34

[0172] Example 34,6-dichloro-2-(2-(piperazin-1-yl)phenoxy)pyrimidine

[0173]

[0174] Step 1) Synthesis of 4-(2-((4,6-dichloropyrimidin-2-yl)oxy)phenyl)piperazine-1-carboxylic acid tert-butyl ester

[0175] Under nitrogen protection, tert-butyl 4-(2-hydroxyphenyl)piperazine-1-carboxylate (0.42g, 1.51mmol), 4,6-dichloro-2-(methylsulfonyl)pyrimidine (0.36g, 1.60mmol) and potassium carbonate (0.42g, 3.02mmol) were added into dichloromethane (10mL), and the reaction solution was reacted at room temperature for 12 hours. After the reaction, the reaction solution was washed with water (20 mL×3), the combined organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column (petroleum ether / ethyl acetate (v / v)=2 / 1) to obtain the title compound as a pale yellow solid (0.32 g, 49.8%).

[0176] MS(ESI,pos.ion)m / z:426.2[M+H] + ;

[0177] 1 HNMR (CDCl 3 ,400MHz)δ(ppm):7.27-...

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Abstract

The invention discloses phenylpiperazine derivatives, a using method thereof and uses of the derivatives, and particularly relates to novel (2-(heteroaryloxy) phenyl)piperazine derivatives and medicine compositions comprising the compounds, wherein the derivatives and the compositions can be used for inhibiting serotonin reuptake. The invention also relates to methods of preparing the compounds and the medicine compositions, and uses of the compounds and the medicine compositions in treatment of central nervous system dysfunction, especially affective disturbance.

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, especially affective disorders, as well as methods and uses thereof. In particular, described herein are phenylpiperazine derivatives that are useful as serotonin reuptake inhibitors. Background technique [0002] 5-HT (serotonin), a neurotransmitter that transmits signals in the brain and nervous system, plays a role in central nervous system (CNS) dysfunction, especially anxiety, depression, aggression and impulsive mood. play an important role. The five-serotonin transporter (5-HTtransporter, 5-HTT / serotonintransporter, SERT) is a transmembrane transporter with high affinity for 5-HT, which reuptakes five-serotonin from the synaptic gap into the presynaptic neuron, directly Affects the concentration of serotonin in the synaptic cleft. [0003] Historically, pharmacological treatment of...

Claims

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Application Information

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IPC IPC(8): C07D239/34C07D239/60C07D239/52A61K31/506A61P25/28A61P25/18A61P25/22A61P25/24
CPCC07D239/34C07D239/52C07D239/60
Inventor 金传飞梁海平张英俊张霁亢宁李勇刘言萍
Owner SUNSHINE LAKE PHARM CO LTD
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