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

Preparation and application of diazaspirodecane piperidine carboxamides

A technology of diazaspiro and decanepiperidine, which is applied in the field of medicine and can solve problems such as threats to human health, increased morbidity and mortality of fungal infections, and low immunity of the body

Active Publication Date: 2022-01-28
SOUTHWEST UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] In recent years, with the rapid development of medical treatment at home and abroad, many intractable diseases have been effectively treated, but due to the abuse of antibiotics, tumor radiotherapy and chemotherapy, organ transplantation anti-rejection and AIDS, the body's immunity is low, making the white The morbidity and mortality of fungal infections caused by common fungi such as Candida, Aspergillus fumigatus, and Cryptococcus neoformans are increasing year by year, which has seriously threatened human health

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
  • Preparation and application of diazaspirodecane piperidine carboxamides
  • Preparation and application of diazaspirodecane piperidine carboxamides
  • Preparation and application of diazaspirodecane piperidine carboxamides

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1、8

[0029] Example 1, Preparation of 8-(2-chloroacetyl)-2,8-diazaspiro[4.5]dec-1-one 4

[0030] Add compound 2 (0.62 g, 4.0 mmol), anhydrous potassium carbonate (0.66 g, 4.8 mmol), dry dichloromethane (15 mL) into a 50 mL round bottom flask, stir at room temperature for 30 min, and add chlorine dropwise in an ice bath Acetyl chloride was a solution of compound 3 (0.4 mL, 4.8 mmol) in dichloromethane (15 mL). Stir overnight at room temperature, then reflux for 30 min, cool to room temperature, add 5% sodium bicarbonate solution (20 mL), stir for 10 min, extract with dichloromethane (25 mL×2), combine organic layers, anhydrous sulfuric acid Sodium drying, suction filtration, vacuum concentration, and column chromatography yielded compound 4 (0.39 g), white powder, yield 42.5%, melting point: 149.7-151.1°C; 1 H NMR (600 MHz, CDCl 3 ) δ 6.62 (s, 1H, CONH), 4.14-4.02 (m, 2H, CH 2 ), 4.01-3.81 (m, 2H, diazaspiro-CH 2 ), 3.35-3.25 (m, 4H, diazaspiro-CH 2 ),2.05-1.96 (m, 2H, diazaspi...

Embodiment 2

[0031] Embodiment 2, the preparation of N-(2-methoxyphenyl)piperidine-4-carboxamide (7a)

[0032] Add 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid, compound 5 (2.35 g, 10.2 mmol), pyridine (2.1 mL, 26.0 mmol), dichloromethane (30 mL ), filled with nitrogen protection, added thionyl chloride (0.9 mL, 12.4 mmol) at room temperature, continued to stir for 30 min, and slowly added dropwise a solution containing o-methoxyaniline (1.42 g, 11.5 mmol), triethylamine (4.9 mL, 35.3 mmol), a catalytic amount of DMAP in dichloromethane solution (30 mL), react at room temperature for 10 h after the dropwise addition, and then add 1 mol / mL hydrochloric acid (30 mL×2), saturated sodium bicarbonate (30 mL ×2) Wash, dry with anhydrous sodium sulfate, filter with suction, concentrate in vacuo, and obtain the intermediate (2.47 g) after column chromatography, add the intermediate (2.47 g) into (50 mL) ethyl acetate, stir and dissolve , add 15% hydrochloric acid (2.5 mL), react at 50°C fo...

Embodiment 3

[0034] Example 3, N-(2-methoxyphenyl)-1-(2-oxo-2-(1-oxo-2,8-diazaspiro[4.5]decane-8-yl) Preparation of ethyl)piperidine-4-carboxamide (1a)

[0035] In a 25 mL round bottom flask, add compound 7a (0.42 g, 1.8 mmol), ground potassium carbonate (0.25 g, 1.8 mmol), catalytic amount of KI (0.07 g, 0.4 mmol), acetonitrile 10 mL, and stir at room temperature After 30 min, compound 4 (0.35 g, 1.5 mmol) was added, heated to 70°C for 8 h, filtered, concentrated in vacuo, and compound 1a (0.25 g) was obtained after column chromatography, a white powder, yield 39.6%, melting point: 136.3-137.5°C; 1 H NMR (600 MHz, CDCl 3 ) δ 8.30 (d, J =7.9 Hz, 1H, CONH), 7.78 (s, 1H, Ar-H), 6.96 (t, J =7.7 Hz, 1H, Ar-H), 6.88 (t, J =7.7 Hz, 1H, Ar-H), 6.80 (d, J =8.1 Hz, 1H, Ar-H), 6.31 (s, 1H,CONH), 3.82(s, 3H, Ar-OCH 3 ), 3.31-3.06 (m, 6H, diazaspiro-CH 2 ), 2.90 (d, J =10.8 Hz, 2H, CH 2 ), 2.20 (dd, J =16.1, 6.9 Hz, 1H, piperidine-CH), 2.12-1.97 (m, 4H, piperidine-CH 2 ), 1.95-1.74 (m, 8H,...

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 discloses 1-oxo-2,8-diazaspiro[4.5]decane piperidine carboxylic acid amide compound and its preparation method and application. The structure of said compound is shown in general formula 1: where R 1 is hydrogen; R 2 For: various substituted aromatic amines. It has been proved by biological activity test experiments that some compounds have certain inhibitory activity against gram-positive bacteria, gram-negative bacteria and fungi, and have obvious inhibitory activity against chitin synthase, with good antibacterial effect, and can be used to prepare anti-pathogenic Microbial medicine. Moreover, the preparation raw material is simple, cheap and easy to obtain, and the application in the aspect of anti-infection is of great significance.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to the design and synthesis of 1-oxo-2,8-diazaspiro[4.5]decanepiperidinecarboxylic acid amide compounds and their application in antimicrobial aspects. Background technique [0002] In recent years, with the rapid development of medical treatment at home and abroad, many intractable diseases have been effectively treated, but due to the abuse of antibiotics, tumor radiotherapy and chemotherapy, organ transplantation anti-rejection and AIDS, the body's immunity is low, making the white The morbidity and mortality of fungal infections caused by common fungi such as Candida, Aspergillus fumigatus, and Cryptococcus neoformans are increasing year by year, which has seriously threatened human health. Therefore, exploring and synthesizing a new type of antibacterial drug has become a research hotspot for scholars in the medical field at home and abroad. [0003] The spiro ring structure...

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): C07D471/10A61P31/10A61P31/04
CPCA61P31/04A61P31/10C07D471/10Y02A50/30
Inventor 吉庆刚李兵王凯渊
Owner SOUTHWEST UNIV
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