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

2-Substituted oxy-5-thiamphenicol aryl piperazine amide analogue and its preparation method and use

A technology of aryl piperazine amides and analogs, applied in the field of 2-substituted oxy-5-methylsulfonyl aryl piperazine amides and their preparation, can solve negative symptoms and cognitive symptoms that are not improved, etc. question

Active Publication Date: 2020-12-01
SHANGHAI HANSOH BIOMEDICAL +1
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs did not improve negative and cognitive symptoms (Sharma, T.; 1999, Br. J. Psychiatry, 1999, 174, 44-51)

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
  • 2-Substituted oxy-5-thiamphenicol aryl piperazine amide analogue and its preparation method and use
  • 2-Substituted oxy-5-thiamphenicol aryl piperazine amide analogue and its preparation method and use
  • 2-Substituted oxy-5-thiamphenicol aryl piperazine amide analogue and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0106] Example 1: (S)-5-(4-(5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxo)nicotyryl)piperazine-1 - base)-2,3-dihydro-1H-inden-1-one preparation

[0107] The first step: preparation of (S)-5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxo)nicotinic acid

[0108]

[0109] Sodium hydride (500 mg, 12.5 mmol) was dissolved in 5 mL of DMF, (S)-trifluoroisopropanol (1.2 g) was added, stirred at room temperature for 30 minutes, and then 2-chloro-5-bromonicotinic acid (900 mg) was added. The system was added, and after stirring at 110 °C for 16 hours, the DMF was spun off, the residue was dissolved in 10 ml of DMSO, and sodium proline (274 mg, 2.0 mmoL), sodium methanesulfinate (1.0 g, 10 mmoL) and iodide were added. Cuprous (761.8 mg, 4.0 mmol), heated to 110 °C and stirred for 4 hours under nitrogen atmosphere, directly separated and purified by reverse phase column chromatography to obtain 5-(methylsulfonyl)-2-((1,1,1- Trifluoropropan-2-yl)oxo)nicotinic acid (150 mg...

Embodiment 2

[0119] Example 2: (S)-(4-(5-Fluoro-3-methylbenzo[d]isoxazol-6-yl)piperazin-1-yl)(5-(methylsulfonyl)-2 Preparation of -((1,1,1-trifluoropropan-2-yl)oxo)phenyl)methanone

[0120] The first step: the preparation of 4-(4-acetyl-2,5-difluorophenyl) piperazine-1-carboxylate tert-butyl ester

[0121]

[0122] Dissolve 2,4,5-trifluoroacetophenone (522 mg, 3.0 mmol) in 10 mL of acetonitrile, then add N-tert-butoxycarbonylpiperazine (671 mg, 3.6 mmol) and potassium carbonate (829 mg, 6.0 mmol), The reaction was heated to reflux overnight. Reversed-phase column chromatography gave the compound 4-(4-acetyl-2,5-difluorophenyl)piperazine-1-carboxylic acid tert-butyl ester (670 mg, 66%). LC-MS:t R =3.12min, [M+H] + 341.2.

[0123] The second step: preparation of tert-butyl 4-(2,5-difluoro-4-(1-(oximinyl)ethyl)phenyl)piperazine-1-carboxylate

[0124]

[0125] 4-(4-Acetyl-2,5-difluorophenyl)piperazine-1-carboxylate tert-butyl ester (670 mg, 1.97 mmol), hydroxylamine hydrochloride (...

Embodiment 3

[0137] Example 3: (S)-(4-(7-Fluoroquinolin-6-yl)piperazin-1-yl)(5-(methylsulfonyl)-2-((1,1,1-trifluoro Preparation of propan-2-yl)oxo)pyridin-3-yl)methanone

[0138] The first step: the preparation of 7-fluoro-6-(piperazin-1-yl)quinoline

[0139]

[0140] Weigh 6-bromo-7-fluoroquinoline (226mg, 1.00mmol), piperazine (129mg, 1.50mmol) and dissolve in 5mL 1,4-dioxane, add bis(tri-tert-butylphosphine) under nitrogen protection Palladium (51 mg, 0.10 mmol) and sodium tert-butoxide (192 mg, 2.00 mmol). Microwave at 120°C for 1 hour. Ethyl acetate was added for extraction, washed with saturated aqueous NaCl solution, and anhydrous Na 2 SO 4 dry. Filtration and concentration gave a tan viscous liquid (210 mg, 91%), and the crude product was directly used in the next reaction.

[0141] The second step: (S)-(4-(7-Fluoroquinolin-6-yl)piperazin-1-yl)(5-(methylsulfonyl)-2-((1,1,1-trifluoro) Preparation of propan-2-yl)oxo)pyridin-3-yl)methanone

[0142]

[0143] Weigh the abo...

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 discloses 2-substituted-oxy-5-methylsulfonyl aryl piperazine acidamide analogue and a preparation method and application thereof, and particularly, relates to 2-substituted-oxy-5-methylsulfonyl aryl piperazine acidamide analogue with a formula (I) compound and a preparation method and application thereof, wherein substitutions in the formula (I) compound are defined as in the description. This serial compound can inhibit the activity of glycine transport protein-1 (GlyT1), is useful in treating related diseases in central nerve and psychological fields, for example, schizophrenia (including positive symptoms, negative symptoms and cognitive symptoms), senile dementia, Parkinson's disease and other related psychological diseases, is widely applicable to the drugs for preventing and treating central nerve and psychological diseases, and is expected to be developed into new-generation GlyT1 inhibitors.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a 2-substituted oxy-5-methylsulfonyl aryl piperazine amide and a preparation method and application thereof. Background technique [0002] Schizophrenia is a progressive and destructive mental illness. According to the symptoms, schizophrenia is usually divided into three symptoms: positive symptoms, negative symptoms and cognitive symptoms. Positive and sexual symptoms manifested as delusions, hallucinations, bizarre behaviors, and thinking disorders; negative symptoms manifested as flat emotion, lack of interest, decreased willpower, and decreased speech; cognitive symptoms manifested as long-term memory, operational memory, and abstraction and planning and speech comprehension and creativity (Lewis, D.A.; Lieberman J.A. Neuron, 2000, 28, 325-33). For decades, the scientific community has focused on the "dopamine hypothesis" that schizophrenia is caused by hyperactive do...

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): C07D261/20C07D413/12C07D417/12C07D275/04C07D231/56C07D401/06C07D295/192C07D405/12C07D307/88C07D401/12C07D215/38C07D217/02C07D217/24A61K31/496A61P25/18A61P25/28A61P25/16
CPCC07D215/38C07D217/02C07D217/24C07D231/56C07D261/20C07D275/04C07D295/192C07D307/88C07D401/06C07D401/12C07D405/12C07D413/12C07D417/12
Inventor 危明松孙兴义张秀春杨飞王少宝廖建春仝朝龙李成海包如迪喻红平徐耀昌
Owner SHANGHAI HANSOH BIOMEDICAL
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