Indole derivative and application thereof

A drug and compound technology, applied in the field of depression and anxiety therapeutic agents, compounds containing indole structure, can solve the problems of slow onset time, low cure rate, increased suicidal tendency, etc., and achieve good inhibitory effect

Active Publication Date: 2022-01-04
CHINA PHARM UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these drugs can alleviate the symptoms of depression to some extent, their slow onset time, weak antidepressant activity, low cure rate, common disease recurr

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
  • Indole derivative and application thereof
  • Indole derivative and application thereof
  • Indole derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] 3-(3-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)propyl)-5-cyano-1H-indole (I-1 )Synthesis

[0029] 1-p-Toluenesulfonyl-3-(3-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)propyl)-5-cyanindole Synthesis of (IV-1)

[0030] Using II-1 (1.0g, 2.7mmol) and 4-piperazinyl-5H-pyrrolo[3,2-d]pyrimidine hydrochloride (III-1, 0.96g, 4.0mmol) as raw materials, triethylamine (5ml), potassium iodide (appropriate amount), and DMF (50ml) were added to a 100ml eggplant-shaped bottle, added to an external temperature of 85°C and reacted for 12h before stopping. After the reaction solution was cooled, it was added to ice water (100ml), extracted with ethyl acetate (40ml×3), the organic layers were combined, washed with saturated brine (50ml×3), dried over anhydrous sodium sulfate, suction filtered, spin-dried, and columnar After separation by chromatography, 0.95 g of an off-white solid was obtained, with a yield of 65.65%.

[0031] 1 H-NMR (300MHz, CDCl 3 )δ(ppm): 1.80~1...

Embodiment 2

[0036] 3-(4-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)butyl)-5-cyano-1H-indole (I-2 )Synthesis

[0037] 1-p-Toluenesulfonyl-3-(4-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)butyl)-5-cyanindole Synthesis of (IV-2)

[0038] With II-2 (1.0g, 2.6mmol), III-1 (0.93g, 3.9mmol), triethylamine (5ml), potassium iodide (appropriate amount), DMF (50ml) as raw materials, the operation process is the same as compound VIII-1, 0.9 g of off-white solid was obtained with a yield of 62.82%.

[0039] 1H-NMR (300MHz, CDCl 3 )δ(ppm): 1.53~1.82(4H,m,-(CH 2 ) 2 CH 2 N3 ), 2.41 (2H, t, J=7.5Hz, ArCH 2 -), 2.51~2.64 (4H, m, piperazine hydrogen), 2.69 (2H, t, J=7.5Hz, -CH 2 N1 =8.6Hz,J 2 =1.5Hz, ArH),7.75(2H,d,J=8.4Hz,ArH),7.84(1H,s,ArH),8.05(1H,d,J=8.6Hz,ArH),8.47(1H,s, ArH).

[0040] 3-(4-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)butyl)-5-cyano-1H-indole (I-2 )Synthesis

[0041] Using IV-2 (1.0g, 1.81mmol), sodium hydroxide (1.1g, 27.2mmol) and methanol (50ml) a...

Embodiment 3

[0044] 3-(5-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)pentyl)-5-cyano-1H-indole (I-3 )Synthesis

[0045] 1-tosyl-3-(5-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)pentyl)-5-cyanindole ( IV-3) Synthesis

[0046] Using II-3 (1.0g, 2.25mmol) and III-1 (0.54g, 2.25mmol) as raw materials, the operation was the same as IV-1 to obtain 0.85g of off-white solid with a yield of 66.71%.

[0047] 1 H-NMR (300MHz, CDCl 3 )δ(ppm): 1.35~1.82(6H,m,-(CH 2 ) 3 CH 2 N3 ),2.40(2H,m,ArCH 2 -), 2.52~2.64 (4H, m, piperazine hydrogen), 2.68 (2H, t, J=7.5Hz, -CH 2 N<), 3.83~3.97 (4H, m, piperazine hydrogen), 6.59 (1H, d, J = 3.2Hz, ArH), 7.25 (2H, d, J = 8.4Hz, ArH), 7.35 (1H, d ,J=3.2Hz,ArH),7.44(1H,s,ArH),7.55(1H,d,J=8.6Hz,ArH),7.75(2H,d,J=8.4Hz,ArH),7.82(1H, s, ArH), 8.05 (1H, d, J=8.6Hz, ArH), 8.47 (1H, s, ArH).

[0048] 3-(5-(4-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)piperazin-1-yl)pentyl)-5-cyano-1H-indole (I-3 )Synthesis

[0049] Add IV-3 (1.0g, 1.76mmol), sodium hydroxide ...

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 relates to the field of medicinal chemistry, and discloses an indole derivative and application thereof. The invention also discloses a composition containing the indole derivative or a pharmaceutically acceptable salt of the compound and a pharmaceutically acceptable carrier, and application of the composition in preparation of multiplex molecules targeting to a 5-hydroxytryptamine receptor and a 5-hydroxytryptamine transporter. The derivative can be used for treating diseases such as depression and anxiety.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a compound (I) containing an indole structure targeting multiple serotonin receptors and serotonin transporters, a preparation method thereof, and a pharmaceutical composition containing such compounds and Use as a treatment for depression and anxiety. Background technique [0002] Depression is a mental illness with morbid emotional changes. The patient may be depressed, have strong sadness and disappointment, refrain from speaking, or be noisy and restless, with high emotions and abnormally increased activities. At present, with the rapid development of society and the acceleration of people's life rhythm, the number of patients suffering from depression is increasing day by day, and the lifetime incidence rate exceeds 5% at least. According to the statistics of the World Health Organization, depression has become the fourth largest disease in the world at presen...

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): C07D487/04A61K31/519A61P25/24A61P25/22
CPCC07D487/04A61P25/24A61P25/22
Inventor 徐云根胡斌段蓉牛静师诗朱启华
Owner CHINA PHARM UNIV
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