Fused ring compound and preparation method and application thereof

A compound and alkyl technology, applied in the field of medicinal chemistry, can solve the problems of no curative effect and low curative effect for patients

Active Publication Date: 2020-12-01
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI +1
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are many drugs on the market in the field of major depression, only about 30-40% of patients respond to first-line treatment
These drugs remain ineffective or poorly effective in more than 30% of patients

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
  • Fused ring compound and preparation method and application thereof
  • Fused ring compound and preparation method and application thereof
  • Fused ring compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0118] Example 1: 2-naphthalene-2-yl octahydropyrrole [3,4-c] pyrrole

[0119]

[0120] step 1:

[0121] 2-Bromonaphthalene 1-a (10.7g, 52mmol, 1.1eq), hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylic acid tert-butyl ester (10g, 47mmol, 1eq) was added to 150mL of toluene , adding Pd to the toluene solution 2 (dba) 3 (2.16g, 2.36mmol, 0.05eq), BINAP (2.35g, 3.78mmol, 0.08eq), potassium tert-butoxide (7.9g, 70.8mmol, 1.5eq), reaction N 2 Protection, heating at an external temperature of 105 degrees for 10 hours. Dilute the reaction solution with 150ml ethyl acetate, filter, wash the filter residue with a small amount of ethyl acetate, wash the filtrate with 300ml saturated sodium chloride solution, dry the organic phase with anhydrous sodium sulfate, and spin dry to obtain 16g of brown oil, add 100ml of ethanol to the oil to make a slurry , a large amount of solids were precipitated, stirred at room temperature for 2 hours, the solids were uniformly dispersed, filtered, an...

Embodiment 2

[0124] Example 2: 2-methyl-5-(naphthalene-2-yl)octahydropyrrole[3,4-c]pyrrole

[0125]

[0126] step 1:

[0127] The product of Example 1 (7.5g, 31.6mmol) was added to 120ml of ethyl formate, triethylamine (17.6ml, 126.6mmol, 4eq) was added, and the system was heated at an external temperature of 60°C for 3h. 100ml of ethyl acetate was diluted, and the organic phase was washed with 200ml of saturated ammonium chloride solution, then washed with 200ml of saturated sodium chloride solution, dried over anhydrous sodium sulfate, and spin-dried to obtain compound 2-a, 8.4g of light yellow solid, yield 99.8%.

[0128] Step 2:

[0129] Compound 2-a (8.4g, 31.6mmol) was added to 120ml of dry tetrahydrofuran, and 1M borane tetrahydrofuran solution (63.2ml, 63.2mmol, 2eq) was added, and the reaction solution gradually dissolved, N 2 Under protection, the external temperature is 68 degrees for 2 hours. The reaction solution was ice-bathed, and 7.9ml of hydrochloric acid (3eq) was ...

Embodiment 3

[0130] Example 3: 5-(Benzo[b]thiophen-4-yl)octahydrocyclopentane[c]pyrrole hydrochloride

[0131]

[0132] step 1:

[0133] Add thionyl chloride (1.2g, 10mmol) dropwise to a solution of 3-a (2.27g, 10mmol) and triethylamine (1.01g, 10mmol) in dichloromethane (30mL) at 0°C, and rise to React at 20°C for 5 hours. Water was added to quench the reaction, the layers were separated, the organic layer was concentrated and subjected to column chromatography (EA:PE=1:15 to 1:5) to obtain compound 3-b (1.25 g, yield 60%).

[0134] Step 2:

[0135] At 0°C, add potassium tert-butoxide to a THF (30 mL) solution of bis-boronic acid pinacol ester (2.54 g, 10 mmol), cuprous chloride (25 mg, 0.25 mmol) and ligand xantphos (145 mg, 0.25 mmol) ( 1.12g, 10mmol), under nitrogen protection, raised to 20°C and reacted for 30min after the addition, then added dropwise a THF (2mL) solution of 3-b (1.23g, 5mmol); reacted overnight at room temperature. The reaction solution was directly added to ...

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 fused ring compound represented by general formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, a preparation method therefor, a pharmaceutical composition, and a use thereof. The compound is used for treating, preventing and / or controlling various nervous system disorders. The compound provided herein modulates one or more monoaminetransporters, inhibits reuptake of endogenous monoamines such as dopamine, serotonin, and norepinephrine (e.g., from synaptic clearances), and / or modulates the 5-HT3 receptor.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry. Specifically, the present invention relates to a ring-connected compound represented by general formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof, its preparation method, its pharmaceutical composition and its preparation and treatment Drug application in diseases of the central nervous system. Background technique [0002] Depression is a widespread, persistent chronic disorder with a lifetime prevalence of approximately 16% worldwide. In the 1950s, isoniazid and imipramine were accidentally discovered clinically to have antidepressant effects, and they became the first-generation drugs for the treatment of depression. Subsequently, the monoamine hypothesis was proposed in pharmacological studies, which believed that the hypofunction of 5-hydroxytryptamine (5-HT) nerves, dopamine (DA) nerves, and norepinephrine (NA) nerves in the brain is the cause of depression. T...

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): C07D487/04C07D409/04C07D209/52C07D405/04A61K31/407A61K31/55A61K31/403A61K31/4709A61P25/04A61P25/22A61P25/24A61P25/00
CPCC07D487/04C07D409/04C07D209/52C07D405/04A61P25/04A61P25/22A61P25/24A61P25/00
Inventor 沈敬山何洋吴春晖杨飞瀑王震张骏驰朱富强覃鸿渐
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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