CN108689983B - 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application - Google Patents

5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application Download PDF

Info

Publication number
CN108689983B
CN108689983B CN201810728335.3A CN201810728335A CN108689983B CN 108689983 B CN108689983 B CN 108689983B CN 201810728335 A CN201810728335 A CN 201810728335A CN 108689983 B CN108689983 B CN 108689983B
Authority
CN
China
Prior art keywords
trichloro
compound
dihydroxy xanthone
dihydroxy
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201810728335.3A
Other languages
Chinese (zh)
Other versions
CN108689983A (en
Inventor
周北斗
阮志鹏
翁智敏
王欣
许桂芬
方圆圆
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Putian University
Original Assignee
Putian University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Putian University filed Critical Putian University
Priority to CN201810728335.3A priority Critical patent/CN108689983B/en
Publication of CN108689983A publication Critical patent/CN108689983A/en
Application granted granted Critical
Publication of CN108689983B publication Critical patent/CN108689983B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • C07D311/84—Xanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
    • C07D311/86—Oxygen atoms, e.g. xanthones
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists

Abstract

The present invention provides a novel compound: 5,7, 8-trichloro-1, 3-dihydroxy xanthone, its preparation method and its application in preparing antineoplastic agent and pharmaceutical composition and inhibiting tyrosinase activity are disclosed.

Description

5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application
Technical Field
The invention relates to the field of medical chemistry, in particular to a 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, a preparation method and application thereof.
Background
Xanthones, also known as xanthones, are the first secondary metabolites isolated from some plants and microorganisms, and contain the parent structure of dibenzo-gamma-pyrones. Xanthone compounds with different structures often have different pharmacological actions or activity degrees. Changes in one or more substituents of the xanthone parent ring can affect its biological activity. The xanthones which have been found to date have a number of important biological activities. Such as antihypertensive, antibacterial, antithrombotic, antitumor, and obesity-suppressing activities.
On the basis of natural medicines, the synthesis of new compounds by chemical means is an important direction for the development of new medicines at present.
Disclosure of Invention
The invention provides a novel 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound and a preparation method thereof, wherein the structure of the compound is shown as the formula (I):
Figure BDA0001720264150000011
the invention also provides a preparation method of the 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, which comprises the following steps: 3,5, 6-trichloro-2-hydroxybenzoic acid, phloroglucinol, phosphorus pentoxide and methanesulfonic acid.
Further, the molar ratio of 3,5, 6-trichloro-2-hydroxybenzoic acid to phloroglucinol was 1: 1.
Further, the method comprises the following steps:
preparing a mixed solution: dissolving phosphorus pentoxide in methanesulfonic acid to prepare a mixed solution; the dissolving temperature is controlled at 105-115 ℃;
and (3) cyclization reaction: adding 3,5, 6-trichloro-2-hydroxybenzoic acid and phloroglucinol into the mixed solution to carry out cyclization reaction to generate 5,7, 8-trichloro-1, 3-dihydroxy xanthone, wherein the reaction temperature is controlled at 88-92 ℃, and the reaction time is controlled at 18-22 min;
solid-liquid separation and purification: and (3) precipitating, filtering and separating by column chromatography to obtain a 5,7, 8-trichloro-1, 3-dihydroxy xanthone finished product after the cyclization reaction is finished.
The inventor also provides the application of the 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound in the aspect of antitumor drugs.
Further, the tumor comprises: hematopoietic stem cell tumor, liver cell tumor, lung cell tumor, breast cell tumor, colon cell tumor.
The inventor also provides an antitumor drug or pharmaceutical composition, which contains 5,7, 8-trichloro-1, 3-dihydroxy xanthone or its pharmaceutically acceptable salt or ester as effective component.
Further, the medicine or the medicine composition comprises tablets, capsules, pills, injections, sustained-release preparations and various microparticle administration systems.
The inventor provides the application of 5,7, 8-trichloro-1, 3-dihydroxy xanthone in the aspects of tyrosinase metabolism regulation medicaments, health products, foods and cosmetics.
In distinction to the prior art, the above technical scheme provides a novel compound: 5,7, 8-trichloro-1, 3-dihydroxy xanthone, its preparation method and its application in preparing antineoplastic agent and inhibiting tyrosinase activity are disclosed.
Detailed Description
In order to explain technical contents, structural features, and objects and effects of the technical means in detail, the following detailed description is given with reference to specific embodiments.
Example 1: synthesis of 5,7, 8-trichloro-1, 3-dihydroxy xanthone
0.68g of phosphorus pentoxide (4.8mmol) and 15mL of methanesulfonic acid (CH)3SO3H) Then, the mixture was added to a 50mL round-bottom flask, heated to 110 ℃ and stirred to dissolve the resulting mixture, and the reaction mixture was cooled to 90 ℃ and then 3,5, 6-trichloro-2-hydroxybenzoic acid (1.6mmol) and 0.20g phloroglucinol (1.6mmol) were added to the mixture, followed by reaction at 90 ℃ for about 20 min. Pouring the reaction liquid into water, separating out solid, carrying out suction filtration, naturally airing, and enabling the primary product to pass through a 200-mesh and 300-mesh pressurized silica gel column by using a mixed solvent of ethyl acetate and petroleum ether to obtain the 5,7, 8-trichloro-1, 3-dihydroxy xanthone, wherein the finished product is an orange-red solid, and the yield is 72%.
IR(KBr)vmax 842,1082,1150,1261,1442,1653,3418cm-1；1H NMR(500MHz,CD3SOCD3)δ6.23(d,1H,J＝2.1Hz,H-2),6.37(d,1H,J＝2.1Hz,H-4),8.39(s,1H,H-6),11.28(s,OH-3),12.54(s,OH-1)；13C NMR(125MHz,CD3SOCD3)δ93.9,99.0,102.6,119.2,121.5,128.7,129.3,134.7,151.3,155.9,162.9,166.2,178.1；HR-ESI-MS:m/z 328.9181[M-H]-(calcd for C13H4Cl3O4,328.9181).
The compound of example 1 can be prepared according to the following procedure:
Figure BDA0001720264150000031
example 2: synthesis of 5,7, 8-trichloro-1, 3-dihydroxy xanthone
0.68g of phosphorus pentoxide (4.8mmol) and 15mL of methanesulfonic acid (CH)3SO3H) Then, the mixture was added to a 50mL round-bottom flask, heated to 105 ℃ and stirred to dissolve the resulting mixture, and the reaction mixture was cooled to 92 ℃ and then 3,5, 6-trichloro-2-hydroxybenzoic acid (1.6mmol) and 0.20g phloroglucinol (1.6mmol) were added to the mixture to react at 92 ℃ for 18 min. Pouring the reaction liquid into water, separating out solid, carrying out suction filtration, naturally airing, and enabling the primary product to pass through a 200-mesh and 300-mesh pressurized silica gel column by using a mixed solvent of ethyl acetate and petroleum ether to obtain the 5,7, 8-trichloro-1, 3-dihydroxy xanthone, wherein the finished product is an orange-red solid.
Example 3: synthesis of 5,7, 8-trichloro-1, 3-dihydroxy xanthone
0.68g of phosphorus pentoxide (4.8mmol) and 15mL of methanesulfonic acid (CH)3SO3H) Then, the mixture was added to a 50mL round-bottom flask, heated to 115 ℃ and stirred to dissolve the resulting mixture, and the reaction mixture was cooled to 88 ℃ and then 3,5, 6-trichloro-2-hydroxybenzoic acid (1.6mmol) and 0.20g phloroglucinol (1.6mmol) were added to the mixture to react at 88 ℃ for 22 min. Pouring the reaction liquid into water, separating out solid, carrying out suction filtration, naturally airing, and enabling the primary product to pass through a 200-mesh and 300-mesh pressurized silica gel column by using a mixed solvent of ethyl acetate and petroleum ether to obtain the 5,7, 8-trichloro-1, 3-dihydroxy xanthone, wherein the finished product is an orange-red solid.
Example 4: antitumor activity test of 5,7, 8-trichloro-1, 3-dihydroxy xanthone (1) principle of detecting cell activity by MTS method: MTS is a novel MTT analogue, is called 3- (4, 5-dimethylthiozol-2-yl) -5 (3-carboxymethyloxyphenyl) -2- (4-sulfopheny) -2H-tetrazolium, and is a yellow dye. Succinate dehydrogenase in the mitochondria of living cells can metabolize and reduce MTS to generate soluble Formazan (Formazan) compounds, and the content of the Formazan can be measured at 490nm by using an enzyme labeling instrument. Since the formazan production amount is generally proportional to the number of living cells, the number of living cells can be estimated from the optical density OD value.
(2) Experimental methods
Inoculating cells: preparing single cell suspension by using culture solution (DMEM or RMPI1640) containing 10% fetal bovine serum, inoculating 3000-15000 cells in each well into a 96-well plate, wherein each well volume is 100 mu l, and the adherent cells are inoculated and cultured 12-24h in advance.
Adding a solution of a compound to be detected: compounds were dissolved in DMSO and compounds were prescreened at a concentration of 40. mu.M, with a final volume of 200. mu.l per well, with 3 replicates per treatment.
③ developing color: after culturing for 48h at 37 ℃, removing culture solution in each hole of the adherent cells, and adding 20 mul of MTS solution and 100 mul of culture solution into each hole; discarding 100 mul of culture supernatant from the suspension cells, and adding 20 mul of MTS solution into each well; 3 blank double wells (mixed solution of 20. mu.l MTS solution and 100. mu.l culture medium) were set, and incubation was continued for 2-4 hours to allow the reaction to proceed sufficiently, and then the light absorption value was measured.
And fourthly, color comparison: selecting 492nm wavelength, reading the light absorption value of each hole by a multifunctional microplate reader (MULTISKAN FC), recording the result, and drawing a tumor cell inhibition rate graph by taking the compound number as the abscissa and the cell inhibition rate as the ordinate after data processing.
The human tumor cells detected are as follows: leukemia HL-60, lung cancer A-549, liver cancer SMMC-7721, breast cancer MCF-7, colon cancer SW480, liver cancer Huh-7, liver cancer HepG2, liver cancer MHCC97H, liver cancer PLC/PRF/5, liver cancer SK-HEP-1 and human normal liver cell HL-7702.
Using cisplatin (DDP) and paclitaxel (Taxol) as positive control compounds, a small amount of 5,7, 8-trichloro-1, 3-dihydroxyxanthone synthesized in example 1 was dissolved in DMSO to prepare a 40. mu.M solution according to the MTS method, and then the inhibitory activity of the tumor cells was examined (Table 1-2).
Inhibitory Activity of the Compounds of Table 1 against 5 tumor cells
Table 1 The inhibitory activities of compound againstfive tumor cells
Figure BDA0001720264150000051
TABLE 2 inhibitory Activity of the Compounds on 6 other hepatocytes
Table 2 The inhibitory activities of compound against the other six liver cells
Figure BDA0001720264150000052
The inhibition rate of the 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound on leukemia HL-60, liver cancer SMMC-7721, breast cancer MCF-7, colon cancer SW480, liver cancer Huh-7, liver cancer HepG2 and liver cancer PLC/PRF/5 is 10-42%. Therefore, the 5,7, 8-trichloro-1, 3-dihydroxy xanthone has a certain degree of inhibitory activity on the tumor cells, and can be applied to preparing antitumor drugs.
Example 5: tyrosinase activity inhibition assay for 5,7, 8-trichloro-1, 3-dihydroxyxanthone compounds
The compound prepared in example 1 (comparative example 1: 6-fluoro-1, 3-dihydroxyxanthone, comparative example 2: 7, 8-difluoro-1, 3-dihydroxyxanthone, comparative example 3: 5-chloro-1, 3-dihydroxyxanthone, comparative example 4: 5, 7-dichloro-1, 3-dihydroxyxanthone); mixing with L-Dopa, adding tyrosinase (final concentration 25U/mL) to start reaction, setting 3 repeat wells, setting blank control containing no drug and Kojic Acid positive control, measuring OD value with microplate reader at room temperature for 5min, and detecting wavelength at 490 nm. And calculating to obtain the tyrosinase activity inhibition rate.
Tyrosinase activity inhibition (%) (1-sample OD)490nm/Experimental control well OD490nm)×100％
TABLE 3 inhibition of tyrosinase by compounds
Table 3 The inhibition oftyrosinase by compound
Figure BDA0001720264150000061
As can be seen from Table 3, the tyrosinase inhibition rates of the halogenated 1, 3-dihydroxyxanthone compounds prepared in comparative examples 1 to 4 were all negative. The tyrosinase inhibition rates of comparative example 4, comparative example 2, comparative example 1 and comparative example 3 were decreased in order. It is shown that 4 compounds prepared in comparative example can be oxidized by tyrosinase, and the oxidized products have absorption of light with 490nm wavelength and absorption intensity higher than that of tyrosine, and it is also indirectly shown that 4 compounds of comparative example can consume tyrosinase. The compound of comparative example 3 is most easily oxidized by tyrosinase, one time for comparative example 1 and one more time for comparative example 2, and one end for comparative example 1.
The tyrosinase inhibition of 5,7, 8-trichloro-1, 3-dihydroxyxanthone, the compound of example 1, was about 22%. Thus, 5,7, 8-trichloro-1, 3-dihydroxyxanthone can inhibit tyrosinase to a greater extent.
The 5,7, 8-trichloro-1, 3-dihydroxy xanthone can be used as tyrosinase regulator, and can be used for preparing tyrosinase regulating medicine and cosmetics.
It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or terminal that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or terminal. Without further limitation, an element defined by the phrases "comprising … …" or "comprising … …" does not exclude the presence of additional elements in a process, method, article, or terminal that comprises the element. Further, herein, "greater than," "less than," "more than," and the like are understood to exclude the present numbers; the terms "above", "below", "within" and the like are to be understood as including the number.
It should be noted that, although the above embodiments have been described herein, the invention is not limited thereto. Therefore, based on the innovative concepts of the present invention, the technical solutions of the present invention can be directly or indirectly applied to other related technical fields by making changes and modifications to the embodiments described herein or by using equivalent structures or equivalent processes performed in the present specification, and are included in the scope of the present invention.

Claims (1)

1, 5,7, 8-trichloro-1, 3-dihydroxy xanthone with chemical structural formula shown in formula (I), and its application in preparing medicine for treating colon cancer SW480 tumor
Figure 954617DEST_PATH_IMAGE001
Ⅰ。
CN201810728335.3A 2018-07-05 2018-07-05 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application Active CN108689983B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810728335.3A CN108689983B (en) 2018-07-05 2018-07-05 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810728335.3A CN108689983B (en) 2018-07-05 2018-07-05 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application

Publications (2)

Publication Number Publication Date
CN108689983A CN108689983A (en) 2018-10-23
CN108689983B true CN108689983B (en) 2021-09-03

Family

ID=63851434

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810728335.3A Active CN108689983B (en) 2018-07-05 2018-07-05 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application

Country Status (1)

Country Link
CN (1) CN108689983B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107698550A (en) * 2017-09-26 2018-02-16 莆田学院 A kind of xanthone compound of 2,4 difluorophenyl substitution and its preparation method and application
CN107759558A (en) * 2017-09-26 2018-03-06 莆田学院 A kind of xanthone compound of trifluoromethyl substitution and its preparation method and application

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107698550A (en) * 2017-09-26 2018-02-16 莆田学院 A kind of xanthone compound of 2,4 difluorophenyl substitution and its preparation method and application
CN107759558A (en) * 2017-09-26 2018-03-06 莆田学院 A kind of xanthone compound of trifluoromethyl substitution and its preparation method and application

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Synthesis and antitumor, antityrosinase, and antioxidant activities of xanthone;B.-D. ZHOU. et al;《Journal of Asian Natural Products Research》;20180330;第20卷(第5期);第467-476页 *

Also Published As

Publication number Publication date
CN108689983A (en) 2018-10-23

Similar Documents

Publication Publication Date Title
CN107759558B (en) Trifluoromethyl substituted xanthone compound and preparation method and application thereof
CN107674083B (en) A kind of preparation method and applications of the L-Leu ring substituent norcantharidin derivative of the structure containing pyridazinone
CN107698550A (en) A kind of xanthone compound of 2,4 difluorophenyl substitution and its preparation method and application
CN109776556B (en) Pyrazolone xanthone skeleton spliced oxindole or benzofuranone compound and preparation method and application thereof
CN108299330B (en) Dehydroabietic acid oxazolidinone derivative and preparation method and application thereof
CN108689983B (en) 5,7, 8-trichloro-1, 3-dihydroxy xanthone compound, preparation method and application
CN111333495B (en) (4-methoxy-3-hydroxyphenyl) (3, 5-dimethyl-2-hydroxyphenyl) ketone, and preparation method and application thereof
CN108997300B (en) 7, 8-difluoro-1, 3-dihydroxy xanthone and preparation method and application thereof
CN108752306B (en) 6-fluoro-1, 3-dihydroxy xanthone and preparation method and application thereof
CN106188080B (en) A kind of D-phenylalanine ring substituent norcantharidin derivative and the preparation method and application thereof
CN106220642B (en) A kind of L-Leu ring substituent norcantharidin derivative and the preparation method and application thereof
CN106083884B (en) A kind of D-Leu ring substituent norcantharidin derivative and the preparation method and application thereof
CN106083873A (en) A kind of L phenylalanine ring substituent norcantharidin derivative and preparation method and application
CN111892486B (en) Hydroxyl-substituted benzophenone compound and preparation method and application thereof
CN114478502A (en) Coumarin compound and synthesis method thereof
CN106188081B (en) A kind of D-Val ring substituent norcantharidin derivative and the preparation method and application thereof
CN111196791A (en) Chiral gamma-butyrolactone derivative and synthesis method and application thereof
CN106046019B (en) A kind of Valine ring substituent norcantharidin derivative and the preparation method and application thereof
CN111004145A (en) Chiral optical amide substituted α -diamino acid derivative and preparation method and application thereof
CN113264873A (en) Etoricoxib purification and preparation method
CN114292224B (en) Cannabidiol-2- (N-acetyl) piperidine acid ester and application thereof
CN113292573B (en) Indolizine chromogen ketone compound with anti-tumor activity and preparation method and application thereof
CN115028643B (en) Pyranoquinoline derivative, preparation method and application thereof
CN107325097B (en) Sinomenine derivate and the preparation method and application thereof
CN115894220A (en) Long-chain compounds acting on ACLY process for their preparation and their use

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant