Novel enol non-steroidal compound as well as preparation method and application thereof

An enol, non-steroidal technology, applied in the field of medicine, can solve the problems of unfavorable application, unsafe, blockage and the like of active agents, and achieve the effect of improving oral bioavailability

Pending Publication Date: 2020-09-08
HC SYNTHETIC PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additionally, poorly soluble active agents are often unfavorable or even unsafe for intravenous administration due to the risk of drug particles clogging blood flow through capillaries

Method used

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  • Novel enol non-steroidal compound as well as preparation method and application thereof
  • Novel enol non-steroidal compound as well as preparation method and application thereof
  • Novel enol non-steroidal compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1: the preparation of compound 1

[0044]

[0045]

[0046] To a stirred solution of 1 (10 g) in anhydrous DCM (300 ml) was added 2 (21.4 g) dropwise at 0°C. The mixture was then stirred at room temperature for 16 hours, and the reaction was quenched with water. The organic layer was washed with sodium hydroxide solution and water, dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was separated by HPLC to afford about 7.86 g of 3 as a white solid.

[0047] at room temperature and N 2 To a solution of 3 (7.5g) in dry DCM (250ml) was added TMSBr (5.65g). The mixture was then stirred for 6 hours and the solvent was removed under reduced pressure. The residue was separated by HPLC to afford compound 1 (5.45 g, 54.5%) as a white solid.

Embodiment 2

[0048] Embodiment 2: the preparation of compound 2

[0049]

[0050]

[0051] To a stirred solution of 1 (10 g) in anhydrous DCM (300 ml) was added 2 (25.8 g) dropwise at 0°C. The mixture was then stirred at room temperature for 16 hours, and the reaction was quenched with water. The organic layer was washed with sodium hydroxide solution and water, dried over anhydrous sodium sulfate, and concentrated to dryness. The residue was separated by HPLC to give about 6.50 g of 5 as a white solid.

[0052] at room temperature and N 2 To a solution of 3 (6.0 g) in dry DCM (200 ml) was added TFA (20 ml). The mixture was then stirred for 6 hours and the solvent was removed under reduced pressure. The residue was separated by HPLC to afford compound 2 (4.57 g, 45.7%) as a white solid.

Embodiment 3

[0053] Embodiment 3: the preparation of compound 3

[0054]

[0055] Add purified water (20ml) and compound 1 (1.5g) into a 100ml reaction flask and stir, then slowly add sodium hydroxide solution (0.278g sodium hydroxide dissolved in 5ml of water) into the compound 1 solution dropwise to adjust the pH of the solution 9.0 to 10.0, filter, slowly add the filtrate to the stirred isopropanol, stir until a large amount of solids are precipitated, then continue to stir for 1 hour, filter, and dry the filter cake under the condition of 30-40°C to obtain the compound 3 is about 0.85g, and the yield is 56.7%.

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PUM

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Abstract

The invention provides a novel enol non-steroidal compound represented by a formula (I) or a a pharmaceutically acceptable salt, hydrate, solvate, polymorph, enantiomer or racemic mixture thereof, wherein m is 0 or 1; n is an integer from 0 to 6; R1 and R2 are independently hydrogen or C1-C6 alkyl or optionally substituted C1-C6 alkyl, halogen, acylamino, sulfonylamino, acyloxy or C(O)R', and R' is hydrogen, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkoxy, aryl C1-C10 alkyl, halogen, acylamino, sulfonylamino or acyloxy; R3 or R4 is independently hydrogen or C1-C6 alkyl or optionally substituted C1-C6 alkyl; R5 or R6 is independently hydrogen, a sodium salt, a potassium salt, a magnesium salt, a calcium salt, an ammonium salt, a meglumine salt, a choline salt, or an amino acid salt. The compound has obvious anti-inflammatory, analgesic and antipyretic effects, and the bioavailability of the compound is obviously higher than that of meloxicam. The invention also provides a preparation methodof the compound, a pharmaceutical composition containing the compound, and pharmaceutical applications of the compound and the pharmaceutical composition.

Description

technical field [0001] The invention belongs to the field of medicine, in particular, the invention relates to a novel enol non-steroidal compound, a preparation method of the compound, a pharmaceutical composition containing the compound, and the compound and the pharmaceutical composition in The preparation is used in treating diseases related to arthritis symptoms. Background technique [0002] Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat acute and chronic pain, inflammation and fever. Some active agents in this category include aspirin, ibuprofen, naproxen, diclofenac, indomethacin, celecoxib, and meloxicam. In 2000, meloxicam was first approved for sale in the United States under the trade name Mobic (Boehringer Ingelheim). It is available as an oral tablet (7.5mg and 15mg) and as an oral suspension (7.5mg / 5ml). Meloxicam is indicated for the treatment of osteoarthritis, rheumatoid arthritis and juvenile rheumatoid arthritis. The recommende...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/6558A61P29/00A61K31/675
CPCC07F9/65583A61P29/00Y02P20/55
Inventor 陆华龙
Owner HC SYNTHETIC PHARMA CO LTD
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