3-pyridinesulfonyl-1-N-heteropyrrole derivatives capable of treating peptic ulcer as well as preparation method and application thereof

A compound and alkoxy technology, applied in the field of 3-pyridinesulfonyl-1-N-heteropyrrole derivatives and their preparation, can solve the problems of easy to cause drug resistance, high recurrence rate of gastric ulcer, high risk and the like

Active Publication Date: 2020-11-17
SICHUAN GUOKANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, studies have found that after taking omeprazole, the recurrence rate of gastric ulcer is high. According to the survey, the recurrence rate of gastric ulcer can reach 90% one year after not taking this drug, which is very dangerous.
Moreover, long-term use

Method used

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  • 3-pyridinesulfonyl-1-N-heteropyrrole derivatives capable of treating peptic ulcer as well as preparation method and application thereof
  • 3-pyridinesulfonyl-1-N-heteropyrrole derivatives capable of treating peptic ulcer as well as preparation method and application thereof
  • 3-pyridinesulfonyl-1-N-heteropyrrole derivatives capable of treating peptic ulcer as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Embodiment 1, the preparation of compound 1

[0084] The synthetic route is:

[0085]

[0086] The specific preparation method is as follows:

[0087] Add 20.0g (144.78mmol) of compound A, 21.2g (144.78mmol) of diethyl oxalate and 100mL of methanol to the reaction flask, cool the system to 0°C, add dropwise 156.4g of 10% sodium methoxide in methanol, at 20-25 Reaction at ℃ for 4h. Then the pH was adjusted to 2-3 with 5% dilute hydrochloric acid, a large amount of solids precipitated out of the system, the filter cake was rinsed with 100 mL of water and then blast-dried to obtain 22.8 g of compound B with a yield of 75.0%. LC / MS m / z=210.1[M] + .

[0088] Take 20.0g (95.15mmol) of compound B, add 100mL of acetic acid and 3.8g (95.15mmol) of 80% hydrazine hydrate, stir overnight at room temperature, add 500mL of water to produce a large amount of white solid, filter, filter the cake with 50mL DIPEA (N,N' -diisopropylethylamine) was beaten, filtered and dried to obt...

Embodiment 2

[0093] Embodiment 2, the preparation of compound 2

[0094] The synthetic route is:

[0095]

[0096] The specific preparation methods include:

[0097] Take 10.0g (28.9mmol) of compound 1, 10.3g (57.8mmol) of NBS (N-bromosuccinimide) and 100mL of DMF, react at 80°C for 6h, add 300mL of water, a large amount of solid precipitates, suction filter, filter cake Rinse with 50mL of water and air-dry at 70°C to obtain 10.0g of compound H, yield 82.0%, LC / MS m / z=426.1[M+H] + .

[0098] Take 4.5g (10.58mmol) of compound H, 2.9g (31.74mmol) of tetramethylammonium fluoride and 50mL of DMF, react at 80°C for 16h, add 150mL of water, a large amount of solid precipitates, filter with suction, and rinse the filter cake with 50mL of water Washed, air-dried at 70°C to obtain 3.0g of compound 2, yield 78.6%, LC / MS m / z=365.1[M+H] + ; 1HNMR(DMSO-d6):2.43(s,3H),3.87(s,2H),7.03-7.12(m,1H),7.16-7.18(m,2H),7.60-7.63(m,1H),7.74- 7.76(m,1H),7.86-7.90(m,1H),8.56-8.57(m,1H),8.87-8.89(m,1H).

Embodiment 3

[0099] Embodiment 3, the preparation of compound 3

[0100] The synthetic route is:

[0101]

[0102] The specific preparation method is:

[0103] Take 4.0g (9.40mmol) of compound H, add 20mL of methanol, cool down to 0°C, add dropwise 12.2g of 5% methanol solution of sodium methoxide, stir at room temperature for 5h, add 100mL of water, extract twice with 200mL of ethyl acetate, take The organic phase was concentrated under reduced pressure, and the concentrate was purified by a silica gel column (the eluent was a mixed solution of dichloromethane:methanol=5:1) to obtain compound 3 with a yield of 80.2%, LC / MS m / z=377.4 [M +H] + ; 1 HNMR(DMSO-d6):2.43(s,3H),3.87(s,2H),3.89(s,3H),7.03-7.12(m,1H),7.16-7.18(m,2H),7.60-7.63( m,1H),7.74-7.76(m,1H),7.86-7.90(m,1H),8.56-8.57(m,1H),8.87-8.89(m,1H).

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Abstract

The invention discloses 3-pyridinesulfonyl-1-N-heteropyrrole derivatives capable of treating peptic ulcer as well as a preparation method and application of the derivative, and particularly provides compounds as shown in a formula I, or pharmaceutically acceptable salts, isotope replacement forms or stereoisomers thereof. Experimental results show that the compounds (especially the compound 4 andthe compound 5) provided by the invention have an excellent inhibition effect on gastric ulcer, can be used for preparing medicines for preventing and/or treating peptic ulcer (especially gastric ulcer), and show wide application prospects.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a 3-pyridinesulfonyl-1-N-heteropyrrole derivative capable of treating peptic ulcer, a preparation method and application thereof. Background technique [0002] Ulcer is a localized defect or ulceration of skin or mucous membrane surface tissue. Its surface is often covered with pus, necrotic tissue or scab, and scars are left after healing. It can be caused by infection, trauma, nodules or tumor ulceration. Peptic ulcer is a common chronic disease. Experimental and clinical studies in recent years have shown that factors such as excessive gastric acid secretion, Helicobacter pylori infection, and weakened gastric mucosal protection are the main causes of peptic ulcer. In addition, gastric excretion Empty delay and bile reflux, the role of gastrointestinal peptides, genetic factors, drug factors, environmental factors and mental factors are also related to the occurre...

Claims

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Application Information

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IPC IPC(8): C07D401/12A61K31/4439A61P1/04
CPCC07D401/12A61P1/04Y02P20/55
Inventor 温万东陈齐石万棋史焱唐伟陈科吴瑕代明星
Owner SICHUAN GUOKANG PHARMA
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