2-nitrophenylsulfonamide derivatives, and preparation method and medical application thereof

A nitro, pharmaceutical technology, applied in the field of 2-nitrophenylsulfonamide derivatives, can solve many problems such as

Inactive Publication Date: 2019-01-22
ZHEJIANG HISUN PHARMA CO LTD
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently published patents on URAT1 inhibitors include WO2011046800, WO2011159839, WO2014183555A1, etc., but not many actually enter the clinic

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-nitrophenylsulfonamide derivatives, and preparation method and medical application thereof
  • 2-nitrophenylsulfonamide derivatives, and preparation method and medical application thereof
  • 2-nitrophenylsulfonamide derivatives, and preparation method and medical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-A

[0048] Synthesis of Example 1-A Compound 1 (Synthetic Method 1)

[0049]

[0050] Synthesis of Intermediate A

[0051] Dissolve 4-aminobenzonitrile (11.8g, 100mmol) in 100ml of acetic acid, add potassium thiocyanate (29.1g, 300mmol) and cool to about 10°C, slowly add liquid bromine (16g, 100mmol) dropwise, after the addition is complete Warm to room temperature and stir for 1 hour. The temperature was raised to 60° C., and the reaction was continued for 6 hours. Concentrate under reduced pressure, evaporate most of the acetic acid, add 100mL water, 200ml ethyl acetate, stir for 0.5 hours, filter with suction, wash with water, dry to obtain intermediate A 2-amino-6-cyanobenzothiazole (12.4g, yield 71%).

[0052] Synthesis of Compound 1 (Synthetic Method 1)

[0053] Dissolve compound A 2-amino-6-cyanobenzothiazole (700mg, 4mmol) in 10ml of pyridine, add 70mg of DMAP, cool to about 0°C with ice water, slowly add 2-nitrobenzene-1-sulfonyl chloride (1.06 g, 4.8mmol, 1.2eq),...

Embodiment 1-B

[0056] Synthesis of Example 1-B Compound 1 (Synthesis Method 2)

[0057]

[0058] Dissolve compound A 2-amino-6-cyanobenzothiazole (700mg, 4mmol) in 7ml toluene, add K 2 CO 3 (1.1g, 8mmol), 2-nitrobenzene-1-sulfonyl chloride (1.06g, 4.8mmol, 1.2eq), heated to reflux for about 10 hours after addition, to compound A 2-amino-6-cyanobenzo Thiazole disappears. Extracted with ethyl acetate, the crude product was separated and purified by silica gel column chromatography, the eluent was petroleum ether: ethyl acetate (V / V) = 1:2, to obtain compound 1 N-(6-cyanobenzothiazole)-2 -yl-(2-nitrophenyl)sulfonamide (1.12 g, yield 78%).

Embodiment 1-C

[0059] Synthesis of Example 1-C Compound 1 (Synthetic Method 3)

[0060]

[0061] Compound A 2-amino-6-cyanobenzothiazole (700mg, 4mmol) was dissolved in 7ml of anhydrous THF, cooled to about -20°C, and LDA / THF solution (4.8mL, 1mol / L, 1.2eq ), continue stirring at this temperature for 0.5 h after the addition, add 2-nitrobenzene-1-sulfonyl chloride (1.06 g, 4.8 mmol, 1.2 eq), and continue stirring at 0 ° C for 2 hours after the addition. Extracted with ethyl acetate, the crude product was separated and purified by silica gel column chromatography, the eluent was petroleum ether: ethyl acetate (V / V) = 1:2, to obtain compound 1N-(6-cyanobenzothiazole)-2- Amyl-(2-nitrophenyl)sulfonamide (1.22 g, yield 85%).

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 medicines related to hyperuricemia and gout and specifically to 2-nitrophenylsulfonamide derivatives as shown in a general formula (I) which is described in the specification, application of the derivatives as URAT1 inhibitors, particularly as therapeutic agents for diseases associated with abnormal uric acid levels, and a preparation method for the derivatives. Each substituent in the general formula (I) is as defined in the specification.

Description

technical field [0001] The invention relates to the field of drugs related to the treatment of hyperuricemia and gout. Specifically, it relates to a 2-nitrophenylsulfonamide derivative, its preparation method and medical application. Background technique [0002] Gout is a chronic metabolic disease characterized by hyperuricemia and pain caused by deposition of monosodium uric acid (MSU) in joints and other parts. The main reason is purine metabolism disorder and / or uric acid excretion disorder. It is estimated that there are more than 20 million gout patients worldwide. Currently, the drugs used to treat gout are very limited: 1) emergency medicine: colchicine tablets, non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids for pain relief; 2) inhibition of uric acid production: allopurinol, side effects febuxostat, ineffective in some patients; 3) Drugs that promote uric acid excretion: benzbromarone, etc., are prone to liver damage and are not suitable for pa...

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): C07D277/82C07D263/58A61K31/423A61K31/428A61K45/06A61P9/12A61P19/06A61P19/02A61P29/00A61P9/00A61P9/10A61P13/12A61P17/06A61P39/02A61P13/04A61P5/20
CPCC07D277/82A61K31/423A61K31/428A61K45/06C07D263/58
Inventor 王亚平郑国君刘礼飞石磊周结波丁芳
Owner ZHEJIANG HISUN PHARMA CO LTD
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