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Pyxinol esterification derivatives having anti-inflammatory activity and preparing method and applications thereof

A technology of derivatives and esterification, which is applied in the field of Pyxinol esterification derivatives and its preparation, can solve serious adverse reactions and other problems, and achieve a strong inhibitory activity effect

Active Publication Date: 2019-05-21
YANTAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, anti-inflammatory drugs in clinical use include non-steroidal anti-inflammatory drugs, steroidal anti-inflammatory drugs, etc. These drugs have played a good role in the treatment of related inflammatory diseases, such as the clinical drug with excellent effect-hydrocortisone Sodium succinate, however, as a glucocorticoid, has obvious serious adverse reactions, such as osteoporosis, etc.

Method used

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  • Pyxinol esterification derivatives having anti-inflammatory activity and preparing method and applications thereof
  • Pyxinol esterification derivatives having anti-inflammatory activity and preparing method and applications thereof
  • Pyxinol esterification derivatives having anti-inflammatory activity and preparing method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] (20S,24R)-epoxy-3β-O-(Boc-glycylglycyl)-dammarane-12β,25-diol (1);

[0034] 20S-Protopanaxadiol (8.000g, 17.36mmol) was dissolved in dichloromethane (160mL), m-CPBA (4.490g, 19.51mmol) was added, and stirred at room temperature for 3h. Dilute with chloroform and wash with water, wash with saturated brine, dry over anhydrous sodium sulfate, filter, concentrate, and column chromatography to obtain Pyxinol[(20S,24R)-epoxydammarin-3β,12β,25-triol] (5.184g , 10.87mmol, 63%).

[0035] Pyxinol, 1 H NMR (400MHz, CDCl 3 )δ3.84(dd, J=8.8,6.8Hz,1H),3.51(td,J=10.5,4.6Hz,1H),3.18(dt,J=9.9,4.5Hz,1H),2.19(td,J =10.9,3.6Hz,1H),1.28(s,3H),1.27(s,3H),1.14–0.96(m,3H),1.09(s,3H),0.98(s,3H),0.97(s, 3H),0.90(s,3H),0.85(s,3H),0.77(s,3H).

[0036] Pyxinol (42mg, 0.088mmol), N-Boc-2-aminoacetic acid (26mg, 0.148mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 51mg, 0.266mmol) was dissolved in anhydrous dichloromethane (1.0mL), in an ice bath, added 4-dimethylam...

Embodiment 2

[0039] (20S,24R)–epoxy–3β–O–(Boc–L-alanylglycyl)–dammarane-12β,25–diol (2)

[0040] The intermediate product (iii) (43mg, 0.067mmol) was dissolved in anhydrous TFA (trifluoroacetic acid, 0.5mL), and reacted at room temperature for 10min to complete the reaction. Its concentrate and Boc-L-alanine (28mg, 0.148mmol) were dissolved in anhydrous dimethylformamide (1mL), HBTU (59mg, 0.156mmol) and 4 drops of triethylamine were added, and stirred at room temperature for 4h. Dilute with ethyl acetate, add saturated aqueous sodium bicarbonate to quench the reaction, extract with ethyl acetate, dry the organic phase over anhydrous sodium sulfate, filter, concentrate, and column chromatography to obtain the target product 2 (44mg, 0.062mmol, 93%) , 1 H NMR (400MHz, CDCl 3 )δ4.54(dd, J=8.8,7.2Hz,1H),4.08(dd,J=18.4,4.8Hz,1H),4.02(dd,J=18.4,4.8Hz,1H),4.04-3.95(m ,1H),3.85(dd,J=9.2,5.6Hz,1H),3.51(td,J=10.4,4.4Hz,1H),2.19(td,J=10.1,3.2Hz,1n),1.46(s, 9H),1.28(s,3H),1.27(s,3H),1.10(s,3H),0....

Embodiment 3

[0042] Detection of inhibitory activity of Pyxinol esterified derivatives on NO production:

[0043] NO is an important inflammatory mediator. When some pathological changes occur in the body, the amount of NO produced in the body will exceed the normal level. Therefore, NO inhibitors have potential possibilities and opportunities to find new ways to treat inflammation-related diseases. In order to evaluate the anti-inflammatory effect of Pyxinol ester derivatives, the level of NO release induced by lipopolysaccharide (LPS) in RAW264.7 cells was detected by Griess reagent. RAW264.7 cells were treated with 1×10 5 Cells / well were seeded in a 96-well plate and cultured for 6 hours; then the model was stimulated with LPS (1 μg / mL), and the cells were treated with 20 μM derivatives, Pyxinol and positive drug (hydrocortisone sodium succinate) 24 Hours later, use Griess reagent (Beyotime, China) to detect the nitrite level to determine the amount of NO production; then measure the...

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Abstract

The invention provides Pyxinol esterification derivatives having anti-inflammatory activity and a preparing method and application thereof, particularly relates to Pyxinol esterification derivatives,a preparing method thereof and anti-inflammatory applications of the derivatives, and belongs to the technical field of novel compound invention, preparation and application. The applications of the derivatives shown as a general formula (I) in preparation of anti-inflammatory medicines or medicine compositions particularly relate to applications in preparation of medicines or medicine compositions for treating and preventing acute lung injuries, septicopyemia and other related diseases. The compounds provided can adopt oral administration, injection and other clinical administration manners.The clinical dosage of the compounds is 0.01-1000 mg / day, and can be increased or decreased according to the state of an illness or dosage forms.

Description

technical field [0001] The invention relates to the fields of medicinal chemistry and pharmaceutical application, in particular to a class of Pyxinol esterified derivatives, a preparation method thereof and an anti-inflammatory application, and belongs to the technical field of proposal, preparation and application of new compounds. Background technique [0002] Inflammation is a defensive response of the body to foreign body stimulation. In most cases, inflammation is beneficial. However, inflammatory factors in the inflammatory process can also directly or indirectly cause damage to healthy tissues, which is clinically manifested as Redness, swelling, heat, pain and other symptoms. On the other hand, many chronic diseases also involve inflammation, such as rheumatoid arthritis. Therefore, inhibiting the production of proinflammatory cytokines has become a therapeutic target for various diseases. Nitric oxide (NO) is an important pro-inflammatory mediator, and excessive N...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J17/00A61K31/58A61P29/00A61P11/00A61P31/04
Inventor 杨刚强孙艺潇房效娟高萌王聪慧高洪艳
Owner YANTAI UNIV
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