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

Triazole compound, pharmaceutical composition, preparation method and uses thereof

A compound, the technology of triazole, which is applied in the field of preparation of antifungal drugs, can solve the problems of low oral bioavailability, low bioavailability, and the curative effect is greatly affected by food, etc.

Inactive Publication Date: 2016-10-19
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, fluconazole has a narrow antibacterial spectrum and is naturally resistant to Candida cruzi and Aspergillus. In recent years, the strains of Candida albicans resistant to fluconazole have also been increasing; The availability is low, and the cyclodextrin contained in its oral solution may cause osmotic diarrhea, which is more harmful to patients with renal insufficiency
The second-generation oral antifungal drug, posaconazole, was launched in 2006 and has expanded antibacterial spectrum, but its metabolic properties and physical and chemical properties are not ideal, especially its extremely low water solubility, resulting in poor oral bioavailability. Low, the curative effect is greatly affected by food, and there are great individual differences among patients, which greatly reduces the stability of curative effect [Expert Opin.Investig.Drugs.2009,18(9),1279-1295]

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
  • Triazole compound, pharmaceutical composition, preparation method and uses thereof
  • Triazole compound, pharmaceutical composition, preparation method and uses thereof
  • Triazole compound, pharmaceutical composition, preparation method and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] Example 1: 2-bromo-5-((2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazole-1- yl)but-2-yl)-4,5-dihydrothieno[3,2-c]pyrrol-6-one (compound 1)

[0106] (a) 5-bromo-3-((((2R,3R)-3-(2,4-difluorophenyl)-3-hydroxyl-4-(1H-1,2,4-triazole-1 -yl)but-2-yl)amino)methyl)thiophene-2-carboxylic acid methyl ester

[0107]

[0108] Dissolve compound 2A [EP332387A1, 1989] (3.21g, 12.00mmol), compound 1-1 [WO2007 / 124546A1, 2007] (4.14g, 13.18mmol) in 60.0ml of acetonitrile, and add After the addition of K2CO3 (1.99g, 14.38mmol), slowly rise to room temperature, stir overnight, concentrate the solvent under reduced pressure, add ethyl acetate and water to extract, the organic layer is washed with saturated brine, dried, filtered, concentrated, column layer Analysis (petroleum ether: ethyl acetate = 4:1 to 2:1) gave an orange-yellow oil, 4.86 g in total, with a yield of 80.7%.

[0109] 1 H NMR (400MHz, CDCl 3 )δ7.89(s,1H),7.75(s,1H),7.36(dd,J=15.6,8.8Hz,1H),7.17(s,1H),6.73(...

Embodiment 2

[0118] Example 2: 5-((2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan- Preparation of 2-yl)-2-(pyridin-3-yl)-4,5-dihydrothieno[3,2-c]pyrrol-6-one (Compound 2)

[0119]

[0120] Compound 1 (99.00mg, 0.21mmol), 3-pyridine borate pinadate (60.00mg, 0.28mmol), tetrakis (triphenylphosphine) palladium (30.00mg, 0.02mmol), cesium carbonate (138.80mg, 0.43mmol ) was dissolved in an aqueous solution of dioxane (15.0ml, 2:1), and reacted at 80°C for 12h under the protection of argon. Concentrate to dryness, add ethyl acetate and water solution, extract the aqueous layer with ethyl acetate, combine the organic layers, wash with saturated brine, dry over anhydrous sodium sulfate, filter, concentrate under reduced pressure, column chromatography (dichloromethane: Methanol=200:1~100:1), 70.00 mg of white solid compound 2 was obtained, and the yield was 71.2%.

[0121] 1 H NMR (500MHz, CDCl 3 )δ8.91(s,1H),8.61(d,J=4.2Hz,1H),7.91(d,J=7.9Hz,1H),7.87(s,1H),7.72(s,1...

Embodiment 3

[0122] Example 3: 5-((2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan- Preparation of 2-yl)-2-(pyridin-4-yl)-4,5-dihydrothieno[3,2-c]pyrrol-6-one (Compound 3)

[0123]

[0124] Compound 1 (99.00mg, 0.21mmol), pyridine-4-boronic acid (34.40mg, 0.28mmol), tetrakis (triphenylphosphine) palladium (30.00mg, 0.02mmol), cesium carbonate (138.80mg, 0.43mmol), Prepared according to a method similar to Example 2, 64.70 mg of white solid compound 3 was obtained, with a yield of 65.6%.

[0125] 1 H NMR (400MHz, CDCl 3)δ8.67(d, J=5.5Hz, 2H), 7.85(s, 1H), 7.72(s, 1H), 7.52(d, J=6.1Hz, 2H), 7.48(s, 1H), 7.43( m,1H),6.83–6.74(m,2H),5.20(d,J=13.6Hz,1H),4.98(d,J=14.3Hz,2H),4.56(d,J=14.3Hz,1H), 4.30(d,J=14.0Hz,1H),1.15(d,J=7.1Hz,3H).MS(EI)m / z:467(M + ).

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 provides a novel triazole compound represented by a general formula (I), an optical isomer, or a pharmaceutically acceptable salt thereof, a composition containing the novel triazole compound, and uses of the novel triazole compound. According to the present invention, the compound has excellent antifungal activity, such that the compound can be used for preparation of drugs for treatment of fungal infectious diseases, particularly deep infectious diseases caused by fungi. The general formula (I) is defined in the specification.

Description

technical field [0001] The invention relates to the fields of drug synthesis and pharmacology. More specifically, it relates to triazole compounds containing nitrogen heterocycles, their pharmaceutical compositions, preparation methods and uses in the preparation of antifungal drugs. Background technique [0002] In the past ten years, due to the continuous increase in the incidence of tumors, the widespread use of bone marrow and organ transplants, and the widespread use of immunosuppressants and broad-spectrum antibiotics, deep fungal infections caused by Candida, Aspergillus, and Cryptococcus neoformans have increased . Systemic deep fungal infection is a serious threat to the life of patients, with a mortality rate as high as 50%, and the fatality rate of deep fungal infection caused by Aspergillus is as high as 90%. In recent years, epidemiological studies have found that the proportion of Aspergillus and other types of Candida (non-albicans) infections has been incre...

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): C07D495/04C07D487/04A61K31/4196A61K31/4439A61K31/506A61K31/541A61K31/4365A61K31/444A61K31/4985A61P31/10
CPCC07D487/04C07D495/04
Inventor 杨玉社徐媛媛曹旭峰潜安然
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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