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

Trimethylsilyl-substituted benzopyran compounds and their applications

A technology of benzopyran and trimethylsilicon, which is applied in the field of chemical medicine, can solve the problems of large cardiovascular side effects, acute analgesic effect is not as good as ibuprofen and the like

Active Publication Date: 2015-08-05
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Selective COX-2 inhibitors such as celecoxib are as effective as NSAIDs for chronic inflammation, but they are less effective than ibuprofen in acute analgesia and have greater cardiovascular side effects

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
  • Trimethylsilyl-substituted benzopyran compounds and their applications
  • Trimethylsilyl-substituted benzopyran compounds and their applications
  • Trimethylsilyl-substituted benzopyran compounds and their applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0172] 2-Trifluoromethyl-7-trimethylsilyl-2H-chromene-3-carboxylic acid

[0173] 2-(trifluoromethyl)-7-(trimethylsilyl)-2H-chromene-3-carboxylic acid

[0174]

[0175] Synthetic route design:

[0176]

[0177] Step 1. 4-Bromo-2-hydroxybenzaldehyde

[0178] 4-bromo-2-hydroxybenzaldehyde

[0179]

[0180] Dissolve 3-bromophenol (3.87g, 22.4mmol) in 30mL of trifluoroacetic acid and stir. When heated to 70°C, slowly add urotropine (3.77g, 26.9mmol). After 2 hours of reaction, add a large amount of water When a solid precipitated, continue to stir for 20 min, then let it stand for 1 h, filter, and obtain 0.9 g (20%) of the product through column chromatography on the obtained solid.

[0181] MS(MM-ES+APCI),m / z:200(M-1)

[0182] Step 2. 7-Bromo-2-trifluoromethyl-2H-chromene-3-carboxylic acid ethyl ester

[0183] ethyl 7-bromo-2-(trifluoromethyl)-2H-chromene-3-carboxylate

[0184]

[0185] Dissolve the above product (0.9g, 4.5mmol) and cesium carbonate (1.47g, 4.5mm...

Embodiment 2

[0199] 2-Trifluoromethyl-5-trimethylsilyl-2H-chromene-3-carboxylic acid

[0200] 2-(trifluoromethyl)-5-(trimethylsilyl)-2H-chromene-3-carboxylic acid

[0201]

[0202] Synthetic route design:

[0203]

[0204] Step 1. 5-Bromo-2-trifluoromethyl-2H-chromene-3-carboxylic acid ethyl ester

[0205] ethyl 5-bromo-2-(trifluoromethyl)-2H-chromene-3-carboxylate

[0206]

[0207] Dissolve 2-bromo-6-hydroxybenzaldehyde (1.00g, 5.0mmol), cesium carbonate (1.63g, 5.0mmol) in 10mL of dry N.N-dimethylformamide (DMF), and heat to 60°C After adding ethyl 4,4,4-trifluorocrotonate (1.68g, 10.0mmol), the temperature was raised to 120°C and the reaction was stirred for 3-4h. When no reactant was detected by mass spectrometry (MS), the reaction was stopped, and water was added. Extracted with ethyl acetate, the extracted organic phase was washed with saturated brine, dried, rotary evaporated under reduced pressure, and 1.20 g (68%) of the product was obtained by column chromatography.

...

Embodiment 3

[0225] 2-Trifluoromethyl-6-trimethylsilyl-2H-chromene-3-carboxylic acid

[0226] 2-(trifluoromethyl)-6-(trimethylsilyl)-2H-chromene-3-carboxylic acid

[0227]

[0228] Step 1. 5-Bromo-2-hydroxybenzaldehyde

[0229] 5-bromo-2-hydroxybenzaldehyde

[0230]

[0231] Dissolve 4-bromophenol (3.81g, 22.0mmol) in 50mL of trifluoroacetic acid and stir. When heated to 70°C, start to slowly add urotropine (3.70g, 26.4mmol). After 2 hours of reaction, add a large amount of water When a solid precipitated out, the mixture was stirred for 20 minutes and left to stand for 1 hour, filtered, and the resulting solid was subjected to column chromatography to obtain 1.59 g (36%) of the product.

[0232] 1 H NMR (CDCl 3 ,400MHz)δ6.91(d,J=8.8Hz,1H),7.60(dd,J 1 =2.4Hz,J 2 =8.8Hz,1H),7.67(d,J=2.4Hz,1H),9.84(s 1H),10.92(s,1H).

[0233] MS (MM-ES+APCI), m / z: 200 (M-1).

[0234] Step 2. Ethyl 6-Bromo-2-trifluoromethyl-2H-chromene-3-carboxylate

[0235] ethyl 6-bromo-2-(trifluoromethyl)-2H...

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 trimethyl silicon substituted benzopyran compound with structural feature of (I), (II) and (III) or salt acceptable in pharmacy or stereoisomer or prodrug molecule thereof. The compound has good anti-inflammatory and analgesia effect, can inhibit the growing of tumors, thus being a novel COX-2 selective inhibitor. The compound and the salt acceptable in pharmacy can be used for preparing medicaments with an anti-inflammatory and analgesia effect or a tumor prevention effect.

Description

technical field [0001] The invention belongs to the field of chemistry and medicine, and in particular relates to a trimethylsilyl-substituted benzopyran compound and its application. Background technique [0002] Traditional non-steroidal anti-inflammatory drugs (traditional NSAIDs or non-selective NSAIDs) are the main anti-inflammatory and analgesic drugs for the treatment of arthritis, including ibuprofen, diclofenac, meloxicam, nabumetone, naproxen and so on. This type of drug is like a "double-edged sword". On the one hand, it has anti-inflammatory and analgesic effects; , perforation and intestinal obstruction. In the United States, about 16,500 people died of gastrointestinal bleeding caused by traditional non-steroidal anti-inflammatory drugs in 1997, equivalent to the number of deaths from AIDS, which increased the medical burden on society and families. Therefore, seeking an anti-inflammatory and analgesic drug that can not only maintain the strong anti-inflammat...

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): C07F7/08A61K31/695A61P29/00A61P35/00A61P19/02A61P19/06A61P19/04A61P37/02A61P17/06A61P17/00A61P1/00A61P1/04A61P25/06A61P7/06A61P9/10A61P3/10A61P21/00A61P27/02A61P31/12A61P11/02A61P1/16A61P1/02A61P25/28A61P7/02A61P31/04A61P35/02
Inventor 张艳梅约翰·泰勒但卫星涂正超陆鑫陈彦
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI