WO2023045612A1 - 一种薁类化合物及其制备方法与应用 - Google Patents
一种薁类化合物及其制备方法与应用 Download PDFInfo
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- WO2023045612A1 WO2023045612A1 PCT/CN2022/111978 CN2022111978W WO2023045612A1 WO 2023045612 A1 WO2023045612 A1 WO 2023045612A1 CN 2022111978 W CN2022111978 W CN 2022111978W WO 2023045612 A1 WO2023045612 A1 WO 2023045612A1
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- compound
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- azulene
- ethyl acetate
- silica gel
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- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- -1 Azulene compound Chemical class 0.000 title claims abstract description 22
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 51
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- 229940125904 compound 1 Drugs 0.000 claims description 30
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
- C07C49/755—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
- C07C2602/30—Azulenes; Hydrogenated azulenes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is usually a protective attempt by the organism to clear away harmful stimuli and initiate the tissue healing process.
- harmful stimuli such as pathogens, damaged cells, or irritants.
- It is usually a protective attempt by the organism to clear away harmful stimuli and initiate the tissue healing process.
- inadequately controlled inflammation can lead to the development of a variety of diseases.
- the body's immune response state is abnormal, it can cause inappropriate or excessive immune response, causing tissue and cell damage and leading to inflammation.
- the present invention also provides the application of the above-mentioned azulene compounds in the preparation of anti-inflammatory drugs.
- Fig. 4 is the 13 C-NMR spectrum of compound 1 of the present invention.
- the chromatographic conditions of the preparative liquid chromatography are: YMC-Triart C18 chromatographic column, chromatographic column size 250*20mm, particle size 5 ⁇ m, flow rate 10ml/min.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Plant Substances (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims (6)
- 一种根据权利要求1所述的薁类化合物的制备方法,其特征在于:包括以下步骤:(1)取紫丁香茎药材,加入乙醇溶液提取,过滤后收集提取液,并将提取液浓缩成浸膏;(2)取浸膏,用水分散后,依次用二氯甲烷、乙酸乙酯萃取,收集两种溶剂萃取液及水液,减压浓缩溶剂,干燥,即得二氯甲烷萃取部位、乙酸乙酯萃取部位、水部位;(3)取步骤(2)得到的乙酸乙酯萃取部位,进行色谱分离纯化,得到所述薁类化合物;步骤(3)中色谱分离纯化具体包括以下步骤:A、取步骤(2)得到的乙酸乙酯萃取部位用甲醇溶解,然后加入硅胶拌样,上样至硅胶柱,进行柱层析分离,用不同体积比的石油醚-丙酮进行梯度洗脱,得到11个馏分1、2、3、4、5、6、7、8、9、10、11;B、取馏分4,经ODS中压制备色谱分离,用不同体积浓度的甲醇-水进行梯度洗脱,得到5个馏分A、B、C、D、E;C、取馏分B经制备液相色谱分离,用体积浓度为13%的乙腈-水洗脱,依据各色谱峰的出峰时间收集馏分,浓缩各馏分,分别得到纯的化合物1、2晶体;步骤A中,拌样所用的硅胶为100-200目,所述乙酸乙酯萃取部位与拌样所用硅胶的质量比为1∶10,所述硅胶柱为200-300目硅胶柱,进行梯度洗脱的石油醚- 丙酮的体积比分别为5∶1、4∶1、3∶1、2∶1、1∶1、0∶1;步骤B中,进行梯度洗脱的甲醇-水的体积浓度分别为5%、15%、30%、50%、70%、100%,所述ODS中压制备色谱的色谱条件为:ODS-C18色谱柱,色谱柱尺寸800*25mm,粒度20-45μm,流速30ml/min,柱温25℃;步骤C中,制备液相色谱的色谱条件为:YMC-Triart C18色谱柱,色谱柱尺寸250*20mm,粒度5μm,流速10ml/min。
- 根据权利要求2所述的薁类化合物的制备方法,其特征在于:步骤(1)中的乙醇溶液为体积浓度为5-95%的乙醇水溶液,所述的提取方法为冷浸法、渗漉法、微波提取法、超声提取法、回流提取法或连续回流提取法。
- 根据权利要求2所述的薁类化合物的制备方法,其特征在于:步骤(1)中的提取次数为1-3次,乙醇溶液的加入量与紫丁香茎药材的质量比为(8-30)∶1;步骤(2)中二氯甲烷、乙酸乙酯萃取的次数分别为4-6次,每次二氯甲烷、乙酸乙酯的用量为被萃取液体积的1/2-1/4。
- 一种根据权利要求1所述的薁类化合物在制备抗炎药物中的应用。
- 根据权利要求5所述的薁类化合物在制备抗炎药物中的应用,其特征在于:将所述薁类化合物直接或间接加入药学上可接受的载体或赋形剂,制备成口服制剂或注射制剂,所述口服制剂为片剂、胶囊剂、颗粒剂、脂肪乳剂、微囊或滴丸,所述注射制剂为注射液或粉针剂。
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