Unlock instant, AI-driven research and patent intelligence for your innovation.

2,3-dihydro-1h-indene-2-ylurea derivative and pharmaceutical application of same

A technology of derivatives and urea, applied in the field of 2,3-dihydro-1H-inden-2-ylurea derivatives and their pharmaceutical applications, can solve the problems of QOL reduction and intractability

Inactive Publication Date: 2014-02-19
TORAY IND INC
View PDF17 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chronic pain is mostly resistant to opioid analgesics, etc., is refractory and persists for a long time, and has abnormal sensations such as hyperalgesia and allodynia, so the QOL of patients is significantly reduced

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
  • 2,3-dihydro-1h-indene-2-ylurea derivative and pharmaceutical application of same
  • 2,3-dihydro-1h-indene-2-ylurea derivative and pharmaceutical application of same
  • 2,3-dihydro-1h-indene-2-ylurea derivative and pharmaceutical application of same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0248] 1-(5-tert-butyl-3-(hydroxymethyl)-2-methoxyphenyl)-3-((1S,2R)-1-hydroxy-2,3-dihydro-1H-indene- Synthesis of 2-yl)urea (compound 1)

[0249]

[0250] 〔the first process〕

[0251] Synthesis of 5-tert-butyl-2-methoxy-3-nitrobenzaldehyde

[0252] A solution of 5-tert-butyl-2-hydroxybenzaldehyde (7.71 g, 43.3 mmol) in acetonitrile (216 mL) was cooled to -40°C, and nitronium tetrafluoroborate (7.47 g, 56.2 mmol) was added. The temperature was raised to -20°C over 1 hour while stirring. Water was added to the reaction liquid, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. To a DMF (50.0 mL) suspension of the obtained residue (8.35 g) and potassium carbonate (25.9 g, 187 mmol) was added iodomethane (8.19 mL, 131 mmol), followed by stirring at room temperature for 15 hours. Water was ad...

Embodiment 2

[0266] 1-(5-tert-butyl-3-(hydroxymethyl)-2-methoxyphenyl)-3-((1S,2R)-4-fluoro-1-hydroxy-2,3-dihydro- Synthesis of 1H-inden-2-yl)urea (Compound 3)

[0267]

[0268] Using 2,2,2-trichloroethyl 5-tert-butyl-3-(hydroxymethyl)-2-methoxyphenylcarbamate (0.100 g, 0.260 mmol) and (1S, 2R)- 2-Amino-4-fluoro-2,3-dihydro-1H-inden-1-ol·L-tartrate (0.091g, 0.286mmol), by carrying out the same reaction as in Example 1 [fifth step], 0.034 g of the title compound was obtained (yield 32%).

Embodiment 3

[0270]1-(5-tert-butyl-2-methoxy-3-((S)-2,2,2-trifluoro-1-hydroxyethyl)phenyl)-3-((1S,2R)- 1-hydroxy-2,3-dihydro-1H-inden-2-yl)urea (compound 46a), 1-(5-tert-butyl-2-methoxy-3-((R)-2,2 , 2-trifluoro-1-hydroxyethyl)phenyl)-3-((1S,2R)-1-hydroxyl-2,3-dihydro-1H-inden-2-yl)urea (compound 46b) synthesis

[0271]

[0272] 〔the first process〕

[0273] Synthesis of 1-(5-tert-butyl-2-methoxy-3-nitrophenyl)-2,2,2-trifluoroethanol

[0274] The solution of 5-tert-butyl-2-methoxy-3-nitrobenzaldehyde (13.5g, 57.1mmol) in THF (57.1mL) was cooled to 0°C, and trimethyl (trifluoromethyl) was added dropwise Silane (10.9 mL, 74.2 mmol), 1.0 mol / L tetra-n-butylammonium fluoride / THF solution (5.71 mL, 5.71 mmol). After adding the reagents, the temperature was raised to room temperature. After stirring for 3 hours, 1 mol / L hydrochloric acid was added to the reaction liquid, and stirred at room temperature for 2 hours. The aqueous layer was extracted with ethyl acetate, and the organic layer ...

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

In order to provide a low molecular weight compound that has p38MAPK inhibitory activity and the accompanying TNF± production suppression activity and that has a favorable pharmacokinetic profile as a pharmaceutical and decreased hepatotoxicity, and to provide a pharmaceutical application of same, disclosed is a 2,3-dihydro-1H-indene-2-yl urea derivative represented below, a pharmacologically acceptable salt thereof, and a therapeutic agent or preventative agent that contains same as an active ingredient and that is for allergic dermatitis, inflammatory bowel disease, and pain.

Description

technical field [0001] The present invention relates to 2,3-dihydro-1H-inden-2-ylurea derivatives and their pharmaceutical use. Background technique [0002] Inflammatory cytokines are biological factors that play an important role in suppressing pathogenic infections, etc., but in the case of excessive production of inflammatory cytokines, it may cause toxic shock syndrome, osteoarthritis, diabetes or inflammation Inflammatory diseases such as venereal enteropathy. [0003] With respect to these inflammatory diseases, studies focusing on biological agents that antagonize the function of tumor necrosis factor α (hereinafter referred to as TNFα), one of the inflammatory cytokines, are currently being actively conducted. For example, infliximab, which is a monoclonal antibody to TNFα, exerts a potent action as an antagonist of TNFα function in vivo, so it has been developed as a therapeutic agent for inflammatory diseases such as Crohn’s disease and uveitis caused by Behcet’s...

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): C07C275/34A61K31/17A61K31/35A61P17/00A61P29/00C07C275/40C07D295/12C07D309/06
CPCC07D309/06C07C275/34C07C275/42C07D295/135C07C2102/08C07C275/40C07C2101/04C07C2601/04C07C2602/08A61P1/04A61P17/00A61P25/04A61P29/00A61P37/08C07D295/12A61K31/17
Inventor 金子浩章河合英树井浦阳介井上秀树戒能美枝目黑裕之内田多鹤
Owner TORAY IND INC