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

3-hydroxypyridine-4-ketone derivative and application thereof in inhibition of renal cell ferroptosis

A technology of hydroxypyridine and picoline, which is applied in the field of medicinal chemistry to achieve the effects of alleviating acute kidney injury, reducing blood urea nitrogen and serum creatinine levels, and inhibiting renal cell ferroptosis

Pending Publication Date: 2022-07-08
ZHEJIANG UNIV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinically, corresponding supportive treatment can only be taken on the premise of clarifying the cause, such as restoring blood volume, suspending the use of nephrotoxic drugs, or accepting renal replacement therapy, etc.

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
  • 3-hydroxypyridine-4-ketone derivative and application thereof in inhibition of renal cell ferroptosis
  • 3-hydroxypyridine-4-ketone derivative and application thereof in inhibition of renal cell ferroptosis
  • 3-hydroxypyridine-4-ketone derivative and application thereof in inhibition of renal cell ferroptosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1. Synthesis of 3-hydroxy-2-methyl-1-phenethylpyridine-4(1H)-one hydrochloride (number CJ-B-01)

[0026]

[0027] 126 mg (1 mmol) of 3-hydroxy-2-methyl-4H-pyrone and 122 mg (1 mmol) of phenylboronic acid were added to the reaction flask, 5 mL of water was added, the mixture was heated to 80 degrees, and 132 μL (1.05 mmol) of phenethylamine was added. , continue to stir the reaction at 80 degrees, and TLC detects the reaction (dichloromethane / methanol=20:3 volume ratio). After the reaction, the reaction solution was spin-dried by a rotary evaporator, 5 mL of concentrated hydrochloric acid was added and stirred at room temperature for 6 h to form a salt, concentrated by rotary evaporation, and 3 mL of acetonitrile was added to obtain the precipitate and suction filtration. Salt product 252 mg, yield 95%.

[0028] White solid, mp: 245.9-246.8℃; 1 H NMR (500MHz, DMSO-d 6 )δ10.40(s, 1H), 8.12(d, J=7.0Hz, 1H), 7.34-7.28(m, 3H), 7.25-7.20(m, 3H), 4.58(t, J=7.4Hz,...

Embodiment 2

[0029] Example 2. Synthesis of 2-ethyl-3-hydroxy-1-phenethylpyridine-4(1H)-one hydrochloride (number CJ-B-02)

[0030]

[0031] 3-hydroxy-2-ethyl-4H-pyrone was used instead of 3-hydroxy-2-methyl-4H-pyrone, the molar weight was unchanged, and the rest were the same as in Example 1, to obtain 257 mg of product, yield 92% .

[0032] White solid, mp: 201.7-202.3℃; 1 H NMR (500MHz, DMSO-d 6 )δ10.53(s,1H),8.12(d,J=7.0Hz,1H),7.31-7.29(m,3H),7.26-7.23(m,1H),7.21-7.20(m,2H),4.56 (t, J=7.4Hz, 2H), 3.11 (t, J=7.3Hz, 2H), 2.86 (q, J=7.4Hz, 2H), 1.14 (t, J=7.5Hz, 3H); 13 C NMR (125MHz, DMSO-d 6 )δ159.0,145.7,142.8,138.2,136.2,129.1,128.7,127.1,110.8,56.2,40.0,39.9,39.7,39.5,39.4,39.2,39.0,36.5,19.6,11.9; HRMS(ESI): m / z calcd forC 15 H 18 NO 2 [M+H] + :244.1332,found:244.1338.

Embodiment 3

[0033] Example 3. Synthesis of 1-(cyclohexylmethyl)-3-hydroxy-2-methylpyridin-4(1H)-one hydrochloride (number CJ-B-03)

[0034]

[0035] The phenethylamine was replaced with cyclohexylmethylamine, the molar weight was unchanged, and the rest were the same as those in Example 1, to obtain 247 mg of the product, with a yield of 96%.

[0036] White solid, mp: 188.7-189.6℃; 1 H NMR (500MHz, DMSO-d 6 )δ10.54(s, 1H), 8.20(dd, J=8.0, 3.0Hz, 1H), 7.40(d, J=6.9Hz, 1H), 4.20(d, J=7.5Hz, 2H), 2.53( s, 3H), 1.80–1.73 (m, 1H), 1.67–1.60 (dd, J=26.1, 9.6Hz, 3H), 1.48–1.46 (d, J=11.7Hz, 2H), 1.20–1.08 (m, 3H), 1.05–0.98 (m, 2H); 13 C NMR (125MHz, DMSO-d 6)δ158.5,143.0,141.5,138.6,110.3,61.2,40.0,39.9,39.7,39.5,39.4,39.2,39.0,37.2,29.3,25.7,25.0,12.8; HRMS(ESI):m / z calcd for C 13 H 20 NO 2 [M+H] + :222.1489,found:222.1485.

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 a 3-hydroxypyridine-4-ketone derivative and application thereof in inhibition of renal cell ferroptosis. The 3-hydroxypyridine-4-ketone derivative comprises a compound with a structure shown as a general formula (I) or (II). Cell results show that such organisms can effectively inhibit ferroptosis of kidney cells. A mouse acute kidney injury model also proves that the actinomycetes can effectively reduce blood urea nitrogen and serum creatinine levels through chelating iron ions, relieve or relieve acute kidney injury, and can be applied to preparation of drugs for treating acute kidney injury;

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a 3-hydroxypyridin-4-one compound and its application in inhibiting renal cell ferroptosis, in particular to an application in the preparation of a drug for inhibiting renal cell ferroptosis, especially in preparation and acute Use in medicines for the treatment of kidney injury-related indications, including the compounds and pharmaceutically acceptable salts thereof. Background technique [0002] Acute renal cell injury is a common clinical emergency, manifesting as sudden and persistent decline in renal function, and it is easy to be converted into chronic kidney disease and end-stage renal disease after acute kidney injury, and it continues to affect more than 100 million people every year. patients, has become a global public health problem in recent years. Patients with acute kidney injury are highly individual and diverse, and there is currently no standard treatment. In...

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): C07D213/69C07D401/12A61P13/12
CPCC07D213/69C07D401/12A61P13/12Y02P20/55
Inventor 陈文腾曹戟岑婕朱海滢何俏军杨波俞永平
Owner ZHEJIANG 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