Hydantoin ibuprofen derivative and synthetic method and application thereof

A derivative, propionyl technology, applied in the field of medicine, can solve the problems of ibuprofen ulcer, bleeding, perforation and so on

Inactive Publication Date: 2012-02-01
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The present invention provides a heinbuprofen derivative, its synthesis method and its use, so as to solve the problems of gastrointestinal ulcer, bleeding and even perforation caused by ibuprofen in use

Method used

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  • Hydantoin ibuprofen derivative and synthetic method and application thereof
  • Hydantoin ibuprofen derivative and synthetic method and application thereof
  • Hydantoin ibuprofen derivative and synthetic method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Preparation of 3-(2-(4-isobutylphenyl) propionyl) imidazolidinyl-2,4-dione (HI-I)

[0027]

[0028] In a 100mL three-necked flask, add 1g of ibuprofen and 5mL of thionyl chloride, heat to reflux for 3h, and evaporate the solution to dryness. Then 0.58 g of hydantoin and 10 mL of pyridine were added to react at room temperature for 12 hours. Evaporation to dryness and column chromatography (methanol:dichloromethane=1:20) gave the product HI-I, 1.12 g of a white solid, with a yield of 80%.

[0029] nuclear magnetic resonance 1 H-NMR (CDCl 3 , 400Hz) δ: 0.87 (d, J=6.64Hz, 6H, 2×CH 3 ), 1.49 (d, J=6.96Hz, 3H, CH 3 ), 1.83(m, 1H, CH), 2.42(d, J=7.16Hz, 2H, CH 2 ), 3.86 (d, J=4.76Hz, 2H, CH 2 ), 4.81(q, J=6.96, 1H, CH), 5.94(s, 1H, NH), 7.07(d, J=8.12Hz, 2H, 2×ArH), 7.15(d, J=8.12Hz, 2H , 2×ArH).

[0030] 13 C-NMR (CDCl 3 , 100Hz) δ: 172.72, 168.52, 154.86, 141.07, 136.43, 129.66, 129.66, 127.61, 127.61, 46.96, 45.71, 44.99, 30.08, 22.35, 22.35, 18.44....

Embodiment 2

[0031] Example 2: Preparation of 1-methyl-3-(2-(4-isobutylphenyl) propionyl) imidazolidinyl-2,4-dione (HI-II)

[0032]

[0033] In a 100mL three-necked flask, add 1g of ibuprofen and 5mL of thionyl chloride, heat to reflux for 3h, and evaporate the solution to dryness. Then 0.67 g of 1-methylhydantoin and 10 mL of pyridine were added, and the mixture was reacted at room temperature for 12 hours. Evaporate to dryness and column chromatography (methanol: methyl chloride = 1:20) to obtain the product HI-II, 1.1 g of a white solid, with a yield of 75%.

[0034] nuclear magnetic resonance 1 H-NMR (CDCl 3 , 400Hz) δ: 0.89 (d, J=6.8Hz, 6H, 2×CH 3 ), 1.49 (d, J=6.8Hz, 3H, CH 3 ), 1.83(m, 1H, CH), 2.42(d, J=7.2Hz, 2H, CH 2 ), 2.93 (s, 3H, CH 3 ), 3.77 (s, 2H, CH 2 ), 4.85 (q, J=6.8Hz, 1H, CH), 7.07 (d, J=8.0Hz, 2H, 2×ArH), 7.16 (d, J=8.0Hz, 2H, 2×ArH).

[0035] 13 C-NMR (CDCl 3 , 100Hz) δ: 172.58, 166.93, 152.86, 140.88, 136.68, 129.57, 129.57, 127.64, 127.64, 50.85, 46.62...

Embodiment 3

[0036] Example 3: Preparation of 1-benzyl-3-(2-(4-isobutylphenyl) propionyl) imidazolidinyl-2,4-dione

[0037]

[0038] In a 100mL three-necked flask, add 1g of ibuprofen and 5mL of thionyl chloride, heat to reflux for 3h, and evaporate the solution to dryness. Then 110 g of 1-benzylhydantoin and 10 mL of pyridine were added, and the mixture was reacted at room temperature for 12 hours. Evaporate to dryness and column chromatography (methanol: dichloromethane = 1:20) to obtain the product HI-II, 1.25 g of oil, yield 68%.

[0039] nuclear magnetic resonance 1 H-NMR (CDCl 3 , 400Hz) δ: 0.89 (d, J=6.56Hz, 6H, 2×CH 3 ), 1.50 (d, J=6.92Hz, 3H, CH 3 ), 1.84(m, 1H, CH), 2.44(d, J=7.16Hz, 2H, CH 2 ), 3.60 (dd, J 1 =17.72Hz,J 2 =25.0Hz, 2H, CH 2 ), 4.46 (dd, J 1 =14.96Hz,J 2 =6.4Hz, 2H, CH 2 ), 4.87 (q, J=6.96Hz, 1H, CH), 7.11 (m, 6H, 6×ArH), 7.32 (m, 3H, 3×ArH).

[0040] 13 C-NMR (CDCl 3 ,100Hz)δ:172.60,166.88,152.84,140.93,136.69,134.42,129.60,129.60,129.02,129.02,12...

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Abstract

The invention relates to a hydantoin ibuprofen derivative and a synthetic method and application thereof, belonging to the field of medicaments. The synthetic method comprises the following steps of: heating and refluxing twice dose of ibuprofen and quintuple dose of thionyl chloride for 3 hours and evaporating to dryness; and adding an appropriate amount of pyridine and 1.2 times dose of hydantoin derivative, reacting at room temperature for 12 hours, evaporating to dryness, and performing chromatography to obtain a 3-(2-(4-isobutyl phenyl) propiono) imidazolidinyl-2,4-diketone derivative. As proved by a pharmacological test, the compound has higher anti-inflammatory activity than ibuprofen serving as a control medicament, and has high cough relieving activity simultaneously.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a new class of 3-(2-(4-isobutylphenyl) propionyl) imidazolidinyl-2,4-dione derivatives and a preparation method thereof, as well as their use in Medicinal use in anti-inflammatory and cough-relieving aspects. Background technique [0002] Non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen is an important drug for the clinical treatment of various inflammations such as rheumatism, rheumatoid arthritis and osteoarthritis, and its main mechanism of action is to inhibit the prostaglandins (PGs) that cause inflammation biosynthesis, thereby improving congestion, swelling, pain and other symptoms at the site of inflammation. However, while ibuprofen inhibits the biosynthesis of PGs in the inflammatory site, it also inhibits the generation of PGs in the gastrointestinal tract that has a protective effect on the gastric mucosa. Therefore, long-term use of this type of drug can ...

Claims

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Application Information

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IPC IPC(8): C07D233/80A61K31/4174A61K31/4166A61P29/00A61P11/14
Inventor 王永生路海滨吴斌孔德娟
Owner JILIN UNIV
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