Andrographolide compounds and preparation method and application thereof

A compound and solvate technology, applied in the field of medicine, can solve the problems of poor selectivity of anti-inflammatory drugs, limited clinical application, obvious side effects, etc., and achieve the effects of good drug resistance, high purity of drugs, and strong anti-inflammatory activity

Active Publication Date: 2020-04-07
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the poor selectivity and obvious side effects of traditional anti-inflammatory drugs, the clinical application is greatly limited.

Method used

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  • Andrographolide compounds and preparation method and application thereof
  • Andrographolide compounds and preparation method and application thereof
  • Andrographolide compounds and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Embodiment 1: the preparation of compound of the present invention

[0057] (1R,2R,4aS,5R)-1(hydroxymethyl)-1,4-dimethyl-6-methylene-5-(2-(naphthalene-1-oxyl)ethyl)decalin Preparation of -2-alcohol (compound 1 for short):

[0058] Andrographolide (15g, 42.8mmol) was placed in a 250mL round bottom flask, 150mL of anhydrous acetone was added, the reaction system was cloudy, then 2,2-dimethoxypropane (15.8mL, 0.13mol) and catalyst were added A certain amount of pyridinium p-toluenesulfonate (PPTS) was reacted at room temperature for 2 hours, and the reaction solution was clear at this time. After the reaction is over, distill off the acetone under reduced pressure, redissolve with dichloromethane (100mL), wash once with saturated sodium bicarbonate (100mL), once with water (100mL), once with saturated brine (100mL), and once with anhydrous sulfuric acid. Sodium dry. 16.2 g of white solid (IM-1) was obtained with a yield of 97%.

[0059] Dissolve IM-1 (14g, 35.8mmol) in...

Embodiment 2

[0065] (1R,2R,4aS,5R)-1(hydroxymethyl)-1,4-dimethyl-6-methylene-5-(2-(4-phenoxyphenoxy)ethyl)deca The preparation of hydronaphthalene-2-ol (abbreviation compound 2):

[0066] The specific operation and proportion refer to the preparation of Compound 1.

[0067] Get (1R,2R,4aS,5R)-1(hydroxymethyl)-1,4-dimethyl-6-methylene-5-(2-(4-phenoxyphenoxy)ethyl) Decalin-2-ol. 1 H-NMR (600MHz, CDCl 3 ):δ7.29(2H,t,J=7.8Hz,3″,5″-H),7.03(1H,t,J=7.2Hz,4″-H),6.94(4H,m,3′, 5′, 2″, 6″-H), 6.83 (2H, d, J=9.0Hz, 2′, 6′-H), 4.87 (1H, s, 13a-H), 4.59 (1H, s, 13b -H), 4.21(1H,d,J=11.4Hz,15a-H),4.02(1H,m,12a-H),3.80(1H,m,12b-H),3.51(1H,m,3- H), 3.34(1H,d,J=11.4Hz,15b-H),2.83(2H,s,7-H),1.26(3H,s,16-H),0.68(3H,s,14-H ). 13 C-NMR (150MHz, CDCl 3 ):δ158.5,155.3,149.9,147.3,129.5,129.5,122.3,120.7,120.7,117.5,117.5,115.4,115.4,107.2,80.6,67.5,64.1,55.2,52.5,482.8,32.8,362.0,37. 23.9, 23.8, 22.6, 15.1.

Embodiment 3

[0069] (1R,2R,4aS,5R)-5-(2-(4-(tert-butyl)phenoxy)ethyl)-1-(hydroxymethyl)-1,4-dimethyl-6-ylidene The preparation of methyl decalin-2-alcohol (abbreviation compound 3):

[0070] The specific operation and proportion refer to the preparation of Compound 1.

[0071] Get (1R,2R,4aS,5R)-5-(2-(4-(tert-butyl)phenoxy)ethyl)-1-(hydroxymethyl)-1,4-dimethyl-6- Methylenedecalin-2-ol. 1 H-NMR (600MHz, CDCl 3 ):δ7.27(2H,d,J=8.4Hz,3′,5′-H),6.79(2H,d,J=9.0Hz,2′,6′-H),4.85(1H,s, 13a-H), 4.58(1H, s, 13b-H), 4.20(1H, d, J=11.4Hz, 15a-H), 4.02(1H, m, 12a-H), 3.79(1H, m, 12b -H),3.50(1H,m,3-H),3.30(1H,d,J=10.2Hz,15b-H),2.88(2H,s,7-H),1.29(9H,s,t- Bu-H), 1.25(3H,s,16-H),0.67(3H,s,14-H). 13 C-NMR (150MHz, CDCl 3 ):δ156.7,147.3,143.1,126.1,126.1,113.8,113.8,107.2,80.6,67.0,64.1,55.2,52.5,42.8,38.9,38.0,36.7,34.0,31.5,31.5,31.5,28.2,24.0, 22.6, 15.1.

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Abstract

The invention belongs to the technical field of medicines, and relates to andrographolide derivatives and a preparation method and application thereof, specifically to novel compounds with anti-inflammatory activity and isomers or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the compounds and a preparation method thereof, and application of the compounds in preparation of medicines for treating and / or preventing inflammation. The compounds and the isomers or pharmaceutically acceptable salts thereof are as shown in a general formula (I) which is described in the specification. In the formula (I), R is as described in the claims and the specification.

Description

technical field [0001] The invention belongs to the technical field of medicine, relates to an andrographolide compound and its preparation method and use, in particular to a new compound with anti-inflammatory activity, its isomer or a pharmaceutically acceptable salt thereof, and a compound containing the compound pharmaceutical composition. It also relates to the preparation method of the compound and the application in the preparation of medicines for treating and / or preventing inflammation. Background technique [0002] Inflammation is a complex defense response of organisms with vascular system to injury factors. When the inflammatory factors act on the body, the body eliminates the inflammatory factors through the inflammatory response, which is a process of injury and anti-injury. Many common diseases (such as autoimmune diseases, atherosclerosis, wound repair, etc.) fall into the category of inflammation. [0003] In recent years, with the continuous deepening of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C43/23C07C43/295C07C41/16C07D311/16C07D311/30C07C205/37C07C201/12A61K31/085A61K31/352A61K31/09A61P29/00
CPCC07C43/23C07C43/295C07D311/16C07D311/30C07C205/37A61P29/00C07C2602/10Y02P20/55
Inventor 陈丽霞李华王望吴艳丽
Owner SHENYANG PHARMA UNIVERSITY
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